Inherited trombophilic states and pulmonary embolism

PubMed Central

Konecny, Filip

2009-01-01

Pulmonary embolism (PE) and deep vein thrombosis (DVT) are associated with considerable morbidity and mortality, mostly, in case of PE for its lack of sensitivity of its early detection. For as much as twenty-five percent of PE patients the primary clinical appearance is unexpected death. While PE is one of the most avertable causes of hospital associated deaths, its diagnostics can be extremely difficult. Newly increased interest in an inherited thrombophilic states has been provoked by the discovery of several common inherited abnormalities, i.e. the prothrombin (PT) gene G20210A, Factor V Leiden (FVL) mutation (Arg506Gln), hyperhomocystenemia and homocysteiuria, Wein-Penzing defect, Sticky Platelet Syndrome (SPS), Quebec platelet disorder (QPD) and Sickle Cell Disease (SCD). PE incidence rates increase exponentially with age for both men and women, as they might harbor more than one thrombophilic state. Although the impact of genetic factors on PE is to some extent documented with lacking taxonomy, its genetic testing as its prevention strategy fall short. In this review thrombophilic states are divided into inherited or acquired, and only the inherited and newly documented are more closely followed. Factors are further grouped based on its thrombophilic taxonomy into; inherited defects of coagulation, inherited defects of fibrinolysis, inherited defects of enzymatic pathway in relation to development of VTE and PE and inherited defects of platelets in relation to PE. It was beyond the scope of this review to follow all inherited and newly recognized factors and its association to VTE and PE; however the overall taxonomy makes this review clinically valuable i.e. in relation to genetic testing as PE prevention. PMID:21772860

Inherited trombophilic states and pulmonary embolism.

PubMed

Konecny, Filip

2009-01-01

Pulmonary embolism (PE) and deep vein thrombosis (DVT) are associated with considerable morbidity and mortality, mostly, in case of PE for its lack of sensitivity of its early detection. For as much as twenty-five percent of PE patients the primary clinical appearance is unexpected death. While PE is one of the most avertable causes of hospital associated deaths, its diagnostics can be extremely difficult. Newly increased interest in an inherited thrombophilic states has been provoked by the discovery of several common inherited abnormalities, i.e. the prothrombin (PT) gene G20210A, Factor V Leiden (FVL) mutation (Arg506Gln), hyperhomocystenemia and homocysteiuria, Wein-Penzing defect, Sticky Platelet Syndrome (SPS), Quebec platelet disorder (QPD) and Sickle Cell Disease (SCD). PE incidence rates increase exponentially with age for both men and women, as they might harbor more than one thrombophilic state. Although the impact of genetic factors on PE is to some extent documented with lacking taxonomy, its genetic testing as its prevention strategy fall short.In this review thrombophilic states are divided into inherited or acquired, and only the inherited and newly documented are more closely followed. Factors are further grouped based on its thrombophilic taxonomy into; inherited defects of coagulation, inherited defects of fibrinolysis, inherited defects of enzymatic pathway in relation to development of VTE and PE and inherited defects of platelets in relation to PE. It was beyond the scope of this review to follow all inherited and newly recognized factors and its association to VTE and PE; however the overall taxonomy makes this review clinically valuable i.e. in relation to genetic testing as PE prevention.

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

PubMed

Carss, Keren J; Arno, Gavin; Erwood, Marie; Stephens, Jonathan; Sanchis-Juan, Alba; Hull, Sarah; Megy, Karyn; Grozeva, Detelina; Dewhurst, Eleanor; Malka, Samantha; Plagnol, Vincent; Penkett, Christopher; Stirrups, Kathleen; Rizzo, Roberta; Wright, Genevieve; Josifova, Dragana; Bitner-Glindzicz, Maria; Scott, Richard H; Clement, Emma; Allen, Louise; Armstrong, Ruth; Brady, Angela F; Carmichael, Jenny; Chitre, Manali; Henderson, Robert H H; Hurst, Jane; MacLaren, Robert E; Murphy, Elaine; Paterson, Joan; Rosser, Elisabeth; Thompson, Dorothy A; Wakeling, Emma; Ouwehand, Willem H; Michaelides, Michel; Moore, Anthony T; Webster, Andrew R; Raymond, F Lucy

2017-01-05

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease. Copyright © 2017. Published by Elsevier Inc.

Lamarck, Evolution, and the Inheritance of Acquired Characters

PubMed Central

Burkhardt, Richard W.

2013-01-01

Scientists are not always remembered for the ideas they cherished most. In the case of the French biologist Jean-Baptiste Lamarck, his name since the end of the nineteenth century has been tightly linked to the idea of the inheritance of acquired characters. This was indeed an idea that he endorsed, but he did not claim it as his own nor did he give it much thought. He took pride instead in advancing the ideas that (1) nature produced successively all the different forms of life on earth, and (2) environmentally induced behavioral changes lead the way in species change. This article surveys Lamarck’s ideas about organic change, identifies several ironies with respect to how his name is commonly remembered, and suggests that some historical justice might be done by using the adjective “Lamarckian” to denote something more (or other) than a belief in the inheritance of acquired characters. PMID:23908372

Center for Inherited Disease Research (CIDR)

Cancer.gov

The Center for Inherited Disease Research (CIDR) Program at The Johns Hopkins University provides high-quality next generation sequencing and genotyping services to investigators working to discover genes that contribute to common diseases.

Ancient origin and maternal inheritance of blue cuckoo eggs.

PubMed

Fossøy, Frode; Sorenson, Michael D; Liang, Wei; Ekrem, Torbjørn; Moksnes, Arne; Møller, Anders P; Rutila, Jarkko; Røskaft, Eivin; Takasu, Fugo; Yang, Canchao; Stokke, Bård G

2016-01-12

Maternal inheritance via the female-specific W chromosome was long ago proposed as a potential solution to the evolutionary enigma of co-existing host-specific races (or 'gentes') in avian brood parasites. Here we report the first unambiguous evidence for maternal inheritance of egg colouration in the brood-parasitic common cuckoo Cuculus canorus. Females laying blue eggs belong to an ancient (∼2.6 Myr) maternal lineage, as evidenced by both mitochondrial and W-linked DNA, but are indistinguishable at nuclear DNA from other common cuckoos. Hence, cuckoo host races with blue eggs are distinguished only by maternally inherited components of the genome, which maintain host-specific adaptation despite interbreeding among males and females reared by different hosts. A mitochondrial phylogeny suggests that blue eggs originated in Asia and then expanded westwards as female cuckoos laying blue eggs interbred with the existing European population, introducing an adaptive trait that expanded the range of potential hosts.

Inheritance on processes, exemplified on distributed termination detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomsen, K.S.

1987-02-01

A multiple inheritance mechanism on processes is designed and presented within the framework of a small object oriented language. Processes are described in classes, and the different action parts of a process inherited from different classes are executed in a coroutine-like style called alternation. The inheritance mechanism is a useful tool for factorizing the description of common aspects of processes. This is demonstrated within the domain of distributed programming by using the inheritance mechanism to factorize the description of distributed termination detection algorithms from the description of the distributed main computations for which termination is to be detected. A clearmore » separation of concerns is obtained, and arbitrary combinations of terminations detection algorithms and main computations can be formed. The same termination detection classes can also be used for more general purposes within distributed programming, such as detecting termination of each phase in a multi-phase main computation.« less

Group I introns are inherited through common ancestry in the nuclear-encoded rRNA of Zygnematales (Charophyceae).

PubMed Central

Bhattacharya, D; Surek, B; Rüsing, M; Damberger, S; Melkonian, M

1994-01-01

Group I introns are found in organellar genomes, in the genomes of eubacteria and phages, and in nuclear-encoded rRNAs. The origin and distribution of nuclear-encoded rRNA group I introns are not understood. To elucidate their evolutionary relationships, we analyzed diverse nuclear-encoded small-subunit rRNA group I introns including nine sequences from the green-algal order Zygnematales (Charophyceae). Phylogenetic analyses of group I introns and rRNA coding regions suggest that lateral transfers have occurred in the evolutionary history of group I introns and that, after transfer, some of these elements may form stable components of the host-cell nuclear genomes. The Zygnematales introns, which share a common insertion site (position 1506 relative to the Escherichia coli small-subunit rRNA), form one subfamily of group I introns that has, after its origin, been inherited through common ancestry. Since the first Zygnematales appear in the middle Devonian within the fossil record, the "1506" group I intron presumably has been a stable component of the Zygnematales small-subunit rRNA coding region for 350-400 million years. PMID:7937917

Genes and inheritance.

PubMed

Middelton, L A; Peters, K F

2001-10-01

The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are introduced and the biochemistry of genetic errors is described.

Environmental Factors Can Influence Mitochondrial Inheritance in the Saccharomyces Yeast Hybrids.

PubMed

Hsu, Yu-Yi; Chou, Jui-Yu

2017-01-01

Mitochondria play a critical role in the generation of metabolic energy and are crucial for eukaryotic cell survival and proliferation. In most sexual eukaryotes, mitochondrial DNA (mtDNA) is inherited from only one parent in non-Mendelian inheritance in contrast to the inheritance of nuclear DNA. The model organism Saccharomyces cerevisiae is commonly used to study mitochondrial biology. It has two mating types: MATa and MATα. Previous studies have suggested that the mtDNA inheritance patterns in hybrid diploid cells depend on the genetic background of parental strains. However, the underlying mechanisms remain unclear. To elucidate the mechanisms, we examined the effects of environmental factors on the mtDNA inheritance patterns in hybrids obtained by crossing S. cerevisiae with its close relative S. paradoxus. The results demonstrated that environmental factors can influence mtDNA transmission in hybrid diploids, and that the inheritance patterns are strain dependent. The fitness competition assay results showed that the fitness differences can explain the mtDNA inheritance patterns under specific conditions. However, in this study, we found that fitness differences cannot fully be explained by mitochondrial activity in hybrids under stress conditions.

Environmental Factors Can Influence Mitochondrial Inheritance in the Saccharomyces Yeast Hybrids

PubMed Central

Hsu, Yu-Yi; Chou, Jui-Yu

2017-01-01

Mitochondria play a critical role in the generation of metabolic energy and are crucial for eukaryotic cell survival and proliferation. In most sexual eukaryotes, mitochondrial DNA (mtDNA) is inherited from only one parent in non-Mendelian inheritance in contrast to the inheritance of nuclear DNA. The model organism Saccharomyces cerevisiae is commonly used to study mitochondrial biology. It has two mating types: MATa and MATα. Previous studies have suggested that the mtDNA inheritance patterns in hybrid diploid cells depend on the genetic background of parental strains. However, the underlying mechanisms remain unclear. To elucidate the mechanisms, we examined the effects of environmental factors on the mtDNA inheritance patterns in hybrids obtained by crossing S. cerevisiae with its close relative S. paradoxus. The results demonstrated that environmental factors can influence mtDNA transmission in hybrid diploids, and that the inheritance patterns are strain dependent. The fitness competition assay results showed that the fitness differences can explain the mtDNA inheritance patterns under specific conditions. However, in this study, we found that fitness differences cannot fully be explained by mitochondrial activity in hybrids under stress conditions. PMID:28081193

Mitochondrial DNA inheritance in the human fungal pathogen Cryptococcus gattii.

PubMed

Wang, Zixuan; Wilson, Amanda; Xu, Jianping

2015-02-01

The inheritance of mitochondrial DNA (mtDNA) is predominantly uniparental in most sexual eukaryotes. In this study, we examined the mitochondrial inheritance pattern of Cryptococcus gattii, a basidiomycetous yeast responsible for the recent and ongoing outbreak of cryptococcal infections in the US Pacific Northwest and British Columbia (especially Vancouver Island) in Canada. Using molecular markers, we analyzed the inheritance of mtDNA in 14 crosses between strains within and between divergent lineages in C. gattii. Consistent with results from recent studies, our analyses identified significant variations in mtDNA inheritance patterns among strains and crosses, ranging from strictly uniparental to biparental. For two of the crosses that showed uniparental mitochondrial inheritance in standard laboratory conditions, we further investigated the effects of the following environmental variables on mtDNA inheritance: UV exposure, temperature, and treatments with the methylation inhibitor 5-aza-2'-deoxycytidine and with the ubiquitination inhibitor ammonium chloride. Interestingly, one of these crosses showed no response to these environmental variables while the other exhibited diverse patterns ranging from complete uniparental inheritance of the MATa parent mtDNA, to biparental inheritance, and to a significant bias toward inheritance of the MATα parental mtDNA. Our results indicate that mtDNA inheritance in C. gattii differs from that in its closely related species Cryptococcus neoformans. Copyright © 2015 Elsevier Inc. All rights reserved.

"What is this genetics, anyway?" Understandings of genetics, illness causality and inheritance among British Pakistani users of genetic services.

PubMed

Shaw, Alison; Hurst, Jane A

2008-08-01

Misconceptions about basic genetic concepts and inheritance patterns may be widespread in the general population. This paper investigates understandings of genetics, illness causality and inheritance among British Pakistanis referred to a UK genetics clinic. During participant observation of genetics clinic consultations and semi-structured interviews in Urdu or English in respondents' homes, we identified an array of environmental, behavioral and spiritual understandings of the causes of medical and intellectual problems. Misconceptions about the location of genetic information in the body and of genetic mechanisms of inheritance were common, reflected the range of everyday theories observed for White British patients and included the belief that a child receives more genetic material from the father than the mother. Despite some participants' conversational use of genetic terminology, some patients had assimilated genetic information in ways that conflict with genetic theory with potentially serious clinical consequences. Additionally, skepticism of genetic theories of illness reflected a rejection of a dominant discourse of genetic risk that stigmatizes cousin marriages. Patients referred to genetics clinics may not easily surrender their lay or personal theories about the causes of their own or their child's condition and their understandings of genetic risk. Genetic counselors may need to identify, work with and at times challenge patients' understandings of illness causality and inheritance.

Semantic similarity measurement between gene ontology terms based on exclusively inherited shared information.

PubMed

Zhang, Shu-Bo; Lai, Jian-Huang

2015-03-01

Quantifying the semantic similarities between pairs of terms in the Gene Ontology (GO) structure can help to explore the functional relationships between biological entities. A common approach to this problem is to measure the information they have in common based on the information content of their common ancestors. However, many studies have their limitations in measuring the information two GO terms share. This study presented a new measurement, exclusively inherited shared information (EISI) that captured the information shared by two terms based on an intuitive observation on the multiple inheritance relationships among the terms in the GO graph. EISI was derived from the information content of the exclusively inherited common ancestors (EICAs), which were screened from the common ancestors according to the attribute of their direct children. The effectiveness of EISI was evaluated against some state-of-the-art measurements on both artificial and real datasets, it produced more relevant results with experts' scores on the artificial dataset, and supported the prior knowledge of gene function in pathways on the Saccharomyces genome database (SGD). The promising features of EISI are the following: (1) it provides a more effective way to characterize the semantic relationship between two GO terms by taking into account multiple common ancestors related, and (2) can quickly detect all EICAs with time complexity of O(n), which is much more efficient than other methods based on disjunctive common ancestors. It is a promising alternative to multiple inheritance based methods for practical applications on large-scale dataset. The algorithm EISI was implemented in Matlab and is freely available from http://treaton.evai.pl/EISI/. Copyright © 2014 Elsevier B.V. All rights reserved.

Non-syndromic posterior lenticonus a cause of childhood cataract: evidence for X-linked inheritance.

PubMed

Russell-Eggitt, I M

2000-12-01

When an X-linked pedigree of posterior lenticonus with cataract was identified further evidence for X-linked inheritance of this condition was sought. Forty-three cases of posterior lenticonus were identified from a database of 354 children with cataract. Two children with the X-linked syndromes of Lowe and Nance-Horan and 3 children with Fanconi syndrome have been excluded from further analysis. None of the children was deaf. None of the non-syndromic cases had microcornea. There were 38 cases of non-syndromic posterior lenticonus (approximately 11%). There were 15 children from 13 pedigrees and 23 apparently sporadic cases. Of the 106 cases on the database with unilateral cataract 15 had posterior lenticonus (approximately 14%). Eleven of 13 pedigrees were compatible with X-linked inheritance or autosomal dominant inheritance with variable expression. However, in 2 pedigrees there was father to son transmission. Posterior lenticonus is a common cause of unilateral infantile cataract, but is thought to be a rare cause of bilateral cataracts. This study suggests that posterior lenticonus is responsible for a significant proportion of childhood cataracts (approximately 14% of unilateral and approximately 9% of bilateral cases). Posterior lenticonus is generally thought to occur as a sporadic condition. This study demonstrates that there is a family history of early-onset cataract in a significant number of bilateral cases (approximately 58%).

Inherited Congenital Cataract: A Guide to Suspect the Genetic Etiology in the Cataract Genesis

PubMed Central

Messina-Baas, Olga; Cuevas-Covarrubias, Sergio A.

2017-01-01

Cataracts are the principal cause of treatable blindness worldwide. Inherited congenital cataract (CC) shows all types of inheritance patterns in a syndromic and nonsyndromic form. There are more than 100 genes associated with cataract with a predominance of autosomal dominant inheritance. A cataract is defined as an opacity of the lens producing a variation of the refractive index of the lens. This variation derives from modifications in the lens structure resulting in light scattering, frequently a consequence of a significant concentration of high-molecular-weight protein aggregates. The aim of this review is to introduce a guide to identify the gene involved in inherited CC. Due to the manifold clinical and genetic heterogeneity, we discarded the cataract phenotype as a cardinal sign; a 4-group classification with the genes implicated in inherited CC is proposed. We consider that this classification will assist in identifying the probable gene involved in inherited CC. PMID:28611546

Elusive inheritance: Transgenerational effects and epigenetic inheritance in human environmental disease.

PubMed

Martos, Suzanne N; Tang, Wan-Yee; Wang, Zhibin

2015-07-01

Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

PubMed Central

Holm, Ingrid A.; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R.; Kinney, Hannah C.; Krous, Henry F.

2014-01-01

Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769

Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

PubMed

Kasper, Burkhard S; Kurzbuch, Katrin; Chang, Bernard S; Pauli, Elisabeth; Hamer, Hajo M; Winkler, Jürgen; Hehr, Ute

2013-06-01

Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH. Copyright © 2013 Wiley Periodicals, Inc.

Ultrasound of Inherited vs. Acquired Demyelinating Polyneuropathies

PubMed Central

Zaidman, Craig M.; Harms, Matthew B.; Pestronk, Alan

2013-01-01

Introduction We compared features of nerve enlargement in inherited and acquired demyelinating neuropathies using ultrasound. Methods We measured median and ulnar nerve cross-sectional areas in proximal and distal regions in 128 children and adults with inherited (Charcot-Marie Tooth-1 (CMT-1) (n=35)) and acquired (Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (n=55), Guillaine-Barre Syndrome (GBS) (n=21) and Multifocal Motor Neuropathy (MMN) (n=17)) demyelinating neuropathies. We classified nerve enlargement by degree and number of regions affected. We defined patterns of nerve enlargement as: none- no enlargement; mild-nerves enlarged but never more than twice normal; regional- nerves normal at at least one region and enlarged more than twice normal at atleast one region; diffuse- nerves enlarged at all four regions with atleast one region more than twice normal size. Results Nerve enlargement was commonly diffuse (89%) and generally more than twice normal size in CMT-1, but not (p<0.001) in acquired disorders which mostly had either no, mild or regional nerve enlargement (CIDP (64%), GBS (95%), and MMN (100%)). In CIDP, subjects treated within three months of disease onset had less nerve enlargement than those treated later. Discussion Ultrasound identified patterns of diffuse nerve enlargement can be used to screen patients suspected of having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede nerve enlargement. PMID:24101129

Effect of heterogeneity and assumed mode of inheritance on lod scores.

PubMed

Durner, M; Greenberg, D A

1992-02-01

Heterogeneity is a major factor in many common, complex diseases and can confound linkage analysis. Using computer-simulated heterogeneous data we tested what effect unlinked families have on a linkage analysis when heterogeneity is not taken into account. We created 60 data sets of 40 nuclear families each with different proportions of linked and unlinked families and with different modes of inheritance. The ascertainment probability was 0.05, the disease had a penetrance of 0.6, and the recombination fraction for the linked families was zero. For the analysis we used a variety of assumed modes of inheritance and penetrances. Under these conditions we looked at the effect of the unlinked families on the lod score, the evaluation of the mode of inheritance, and the estimate of penetrance and of the recombination fraction in the linked families. 1. When the analysis was done under the correct mode of inheritance for the linked families, we found that the mode of inheritance of the unlinked families had minimal influence on the highest maximum lod score (MMLS) (i.e., we maximized the maximum lod score with respect to penetrance). Adding sporadic families decreased the MMLS less than adding recessive or dominant unlinked families. 2. The mixtures of dominant linked families with unlinked families always led to a higher MMLS when analyzed under the correct (dominant) mode of inheritance than when analyzed under the incorrect mode of inheritance. In the mixtures with recessive linked families, assuming the correct mode of inheritance generally led to a higher MMLS, but we observed broad variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic instability in inherited and sporadic leukemias.

PubMed

Popp, Henning D; Bohlander, Stefan K

2010-12-01

Genetic instability due to increased DNA damage and altered DNA repair is of central significance in the initiation and progression of inherited and sporadic human leukemias. Although very rare, some inherited DNA repair insufficiency syndromes (e.g., Fanconi anemia, Bloom's syndrome) have added substantially to our understanding of crucial mechanisms of leukemogenesis in recent years. Conversely, sporadic leukemias account for the main proportion of leukemias and here DNA damaging reactive oxygen species (ROS) play a central role. Although the exact mechanisms of increased ROS production remain largely unknown and no single pathway has been detected thus far, some oncogenic proteins (e.g., the activated tyrosine kinases BCR-ABL1 and FLT3-ITD) seem to play a key role in driving genetic instability by increased ROS generation which influences the disease course (e.g., blast crisis in chronic myeloid leukemia or relapse in FLT3-ITD positive acute myeloid leukemia). Of course other mechanisms, which promote genetic instability in leukemia also exist. A newly emerging mechanism is the genome-wide alteration of epigenetic marks (e.g., hypomethylation of histone H3K79), which promotes chromosomal instability. Taken together genetic instability plays a critical role both in inherited and sporadic leukemias and emerges as a common theme in both inherited and sporadic leukemias. Beyond its theoretical impact, the analysis of genetic instability may lead the way to the development of innovative therapy strategies. © 2010 Wiley-Liss, Inc.

Alport syndrome: impact of digenic inheritance in patients management.

PubMed

Fallerini, C; Baldassarri, M; Trevisson, E; Morbidoni, V; La Manna, A; Lazzarin, R; Pasini, A; Barbano, G; Pinciaroli, A R; Garosi, G; Frullanti, E; Pinto, A M; Mencarelli, M A; Mari, F; Renieri, A; Ariani, F

2017-07-01

Alport syndrome (ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance (DI). Here we present a new series of families with DI and we discuss the consequences for genetic counseling and risk assessment. Out of five families harboring variants in more than one COL4 gene detected by next generation sequencing (NGS), minigene-splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family, a de novo mutation (COL4A5) combined with an inherited mutation (COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of DI in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inherited metabolic disorders in Thailand.

PubMed

Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

2002-08-01

The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

Constitutional delay of puberty: presentation and inheritance pattern in 48 familial cases.

PubMed

Winter, Sarah; Ousidhoum, Aldjia; McElreavey, Kenneth; Brauner, Raja

2016-03-12

The mechanism that initiates the onset of puberty is largely unknown but the age of onset is mainly under genetic control and influenced by environmental factors including nutrition. Familial forms of constitutional delay of puberty (CDP) suggest the involvement of genetic factors. The purpose of this study is to describe the presentation and the mode of inheritance of CDP in a series of familial cases. A retrospective, single center study was carried out over 10 years on 48 probands (14 girls and 34 boys) from 48 families seen for CDP with a familial component. Of the 48 probands, 46 (96 %) had at least one affected 1(st) degree relatives and 2 (4 %, 2 boys) had only 2(nd) degree relatives affected. In girls, 11 families (79 %) exhibited exclusive maternal inheritance, 1 (7 %) paternal inheritance and 2 (14 %) both maternal and paternal inheritance. In boys, 14 families (41 %) exhibited exclusive maternal inheritance, 12 (35 %) paternal inheritance and 8 (24 %) both maternal and paternal inheritance. In the boys with bilineal inheritance, the ages at onset of puberty (16 ± 1.41 years) and at evaluation (16.05 ± 2.47 years) were higher than in those with unilineal inheritance (15.25 ± 0.35 and 15.1 ± 0.42 years respectively), but the difference was not significant. In girls exclusive maternal inheritance seems to be the major mode of inheritance whereas for boys the mode of inheritance was almost equally maternal, paternal or bilineal. Clinical phenotype of boys with bilineal inheritance seems to be more severe, but the difference did not reach statistical significance, perhaps because of the small sample size. This greater severity of the phenotype in boys with bilineal inheritance is likely due to inheriting different puberty timing genes from each parent. Future research should be directed at identifying such genes.

Atypical mitochondrial inheritance patterns in eukaryotes.

PubMed

Breton, Sophie; Stewart, Donald T

2015-10-01

Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

Common variants in Mendelian kidney disease genes and their association with renal function.

PubMed

Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

2013-12-01

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

PubMed Central

Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

2013-01-01

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

Inherited secondary nephrogenic diabetes insipidus: concentrating on humans.

PubMed

Bockenhauer, D; Bichet, D G

2013-04-15

The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.

A Novel Nonsense Mutation in the DMP1 Gene Identified by a Genome-Wide Association Study Is Responsible for Inherited Rickets in Corriedale Sheep

PubMed Central

Blair, Hugh T.; Thompson, Keith G.; Rothschild, Max F.; Garrick, Dorian J.

2011-01-01

Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies implicate inheritance as a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep comprising 17 affected and 3 carriers. A homozygous region of 125 consecutive single-nucleotide polymorphism (SNP) loci was identified in all affected sheep, covering a region of 6 Mb on ovine chromosome 6. Among 35 candidate genes in this region, the dentin matrix protein 1 gene (DMP1) was sequenced to reveal a nonsense mutation 250C/T on exon 6. This mutation introduced a stop codon (R145X) and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed all 17 affected sheep were “T T” genotypes; the 3 carriers were “C T”; 24 phenotypically normal related sheep were either “C T” or “C C”; and 46 unrelated normal control sheep from other breeds were all “C C”. The other SNPs in DMP1 were not concordant with the disease and can all be ruled out as candidates. Previous research has shown that mutations in the DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective “T” allele. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis. PMID:21747952

Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.

PubMed

Crompton, Douglas E; Scheffer, Ingrid E; Taylor, Isabella; Cook, Mark J; McKelvie, Penelope A; Vears, Danya F; Lawrence, Kate M; McMahon, Jacinta M; Grinton, Bronwyn E; McIntosh, Anne M; Berkovic, Samuel F

2010-11-01

Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T₂ signal on magnetic resonance imaging. Compelling evidence of a genetic aetiology (rather than chance aggregation) in familial mesial temporal lobe epilepsy has come from twin studies. Dominant inheritance has been reported in two large families, though the usual mode of inheritance is not known. Here, we describe clinical and neurophysiological features of 20 new mesial temporal lobe epilepsy families including 51 affected individuals. The epilepsies in these families were generally benign, and febrile seizure history was infrequent (9.8%). No evidence of hippocampal sclerosis or dysplasia was present on brain imaging. A single individual underwent anterior temporal lobectomy, with subsequent seizure freedom and histopathological evidence of hippocampal sclerosis was not found. Inheritance patterns in probands' relatives were analysed in these families, together with 19 other temporal lobe epilepsy families previously reported by us. Observed frequencies of epilepsies in relatives were lower than predicted by dominant Mendelian models, while only a minority (8/39) of families could be compatible with recessive inheritance. These findings strongly suggest that complex inheritance, similar to that widely accepted in the idiopathic generalized epilepsies, is the usual mode of inheritance in familial mesial temporal lobe epilepsy. This disorder, which appears to be

Inherited Mitochondrial Diseases of DNA Replication

PubMed Central

Copeland, William C.

2007-01-01

Mitochondrial genetic diseases can result from defects in mitochondrial DNA (mtDNA) in the form of deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These mutations may be spontaneous, maternally inherited, or a result of inherited nuclear defects in genes that maintain mtDNA. This review focuses on our current understanding of nuclear gene mutations that produce mtDNA alterations and cause mitochondrial depletion syndrome (MDS), progressive external ophthalmoplegia (PEO), ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). To date, all of these etiologic nuclear genes fall into one of two categories: genes whose products function directly at the mtDNA replication fork, such as POLG, POLG2, and TWINKLE, or genes whose products supply the mitochondria with deoxynucleotide triphosphate pools needed for DNA replication, such as TK2, DGUOK, TP, SUCLA2, ANT1, and possibly the newly identified MPV17. PMID:17892433

Disomic Inheritance and Segregation Distortion of SSR Markers in Two Populations of Cynodon dactylon (L.) Pers. var. dactylon

PubMed Central

Guo, Yuanwen; Wu, Yanqi; Anderson, Jeff A.; Moss, Justin Q.; Zhu, Lan

2015-01-01

Common bermudagrass [C. dactylon (L.) Pers. var. dactylon] is economically and environmentally the most important member among Cynodon species because of its extensive use for turf, forage and soil erosion control in the world. However, information regarding the inheritance within the taxon is limited. Accordingly, the objective of this study was to determine qualitative inheritance mode in common bermudagrass. Two tetraploid (2n = 4x = 36), first-generation selfed (S1) populations, 228 progenies of ‘Zebra’ and 273 from A12359, were analyzed for segregation with 21 and 12 simple sequence repeat (SSR) markers, respectively. It is concluded that the inheritance mode of tetraploid bermudagrass was complete or near complete disomic. It is evident that the two bermudagrass parents had an allotetraploid genome with two distinct subgenomes since 33 SSR primer pairs amplified 34 loci, each having two alleles. Severe transmission ratio distortions occurred in the Zebra population while less so in the A12359 population. The findings of disomic inheritance and segregation ratio distortion in common bermudagrass is significant in subsequent linkage map construction, quantitative trait locus mapping and marker-assisted selection in the species. PMID:26295707

Disomic Inheritance and Segregation Distortion of SSR Markers in Two Populations of Cynodon dactylon (L.) Pers. var. dactylon.

PubMed

Guo, Yuanwen; Wu, Yanqi; Anderson, Jeff A; Moss, Justin Q; Zhu, Lan

2015-01-01

Common bermudagrass [C. dactylon (L.) Pers. var. dactylon] is economically and environmentally the most important member among Cynodon species because of its extensive use for turf, forage and soil erosion control in the world. However, information regarding the inheritance within the taxon is limited. Accordingly, the objective of this study was to determine qualitative inheritance mode in common bermudagrass. Two tetraploid (2n = 4x = 36), first-generation selfed (S1) populations, 228 progenies of 'Zebra' and 273 from A12359, were analyzed for segregation with 21 and 12 simple sequence repeat (SSR) markers, respectively. It is concluded that the inheritance mode of tetraploid bermudagrass was complete or near complete disomic. It is evident that the two bermudagrass parents had an allotetraploid genome with two distinct subgenomes since 33 SSR primer pairs amplified 34 loci, each having two alleles. Severe transmission ratio distortions occurred in the Zebra population while less so in the A12359 population. The findings of disomic inheritance and segregation ratio distortion in common bermudagrass is significant in subsequent linkage map construction, quantitative trait locus mapping and marker-assisted selection in the species.

CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING.

PubMed

Hafler, Brian P

2017-03-01

Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies.

Online Mendelian Inheritance in Man (OMIM).

PubMed

Hamosh, A; Scott, A F; Amberger, J; Valle, D; McKusick, V A

2000-01-01

Online Mendelian Inheritance In Man (OMIM) is a public database of bibliographic information about human genes and genetic disorders. Begun by Dr. Victor McKusick as the authoritative reference Mendelian Inheritance in Man, it is now distributed electronically by the National Center for Biotechnology Information (NCBI). Material in OMIM is derived from the biomedical literature and is written by Dr. McKusick and his colleagues at Johns Hopkins University and elsewhere. Each OMIM entry has a full text summary of a genetic phenotype and/or gene and has copious links to other genetic resources such as DNA and protein sequence, PubMed references, mutation databases, approved gene nomenclature, and more. In addition, NCBI's neighboring feature allows users to identify related articles from PubMed selected on the basis of key words in the OMIM entry. Through its many features, OMIM is increasingly becoming a major gateway for clinicians, students, and basic researchers to the ever-growing literature and resources of human genetics. Copyright 2000 Wiley-Liss, Inc.

Inheritance of resistance to the bean-pod weevil (Apion godmani Wagner) in common beans from Mexico.

PubMed

Garza, R; Cardona, C; Singh, S P

1996-03-01

The bean-pod weevil (BPW), Apion godmani Wagner, often causes heavy losses in crops of common bean (Phaseolus vulgaris L.). Farmers need resistant bean cultivars to minimize losses, cut production costs, stabilize seed yield, and reduce pesticide use and consequent health hazards. To design effective breeding methods, breeders need new and better sources of resistance and increased knowledge of their modes of inheritance. We therefore: (1) compared sources of resistance to BPW, (2) studied the inheritance of resistance, and (3) determined whether the sources possess similar or different genes for BPW resistance. The following sources of resistance, originating from the Mexican highlands, were evaluated for 3 years at INIFAP-Santa Lucía de Prias, Texcoco, Mexico: 'Amarillo 153', 'Amarillo 169', 'Hidalgo 58', 'J 117', 'Pinto Texcoco', 'Pinto 168', and 'Puebla 36'. All except 'Puebla 36' were crossed with the susceptible cultivar 'Jamapa'. 'Amarillo 153' and 'Puebla 36' were crossed with another susceptible cultivar, 'Bayo Mex'. The parents, F1 hybrids, and F2 populations were evaluated for BPW damage in 1992. Backcrosses of the F1 of Jamapa/Pinto 168 to the respective susceptible and resistant parents were also evaluated in 1992. All seven resistant accessions were crossed in all possible combinations, excluding reciprocals. The resulting 21 F1 hybrids and 21 F2 populations were evaluated for BPW damage in 1994. 'J 117' had the highest level of resistance to BPW. 'Pinto Texcoco' and 'Puebla 36' had the highest mean damage score of all seven sources of resistance. The F1 hybrids between susceptible parents and resistant sources were generally intermediate. Two genes segregating independently controlled the BPW resistance in each accession. One gene, Agm, has no effect when present alone, whereas the other gene, Agr, alone conferred intermediate resistance. When both genes were present, resistance to BPW was higher. Based on mean BPW damage scores, all 21 F1 hybrids

Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites.

PubMed

Ben Maamar, Millissia; Sadler-Riggleman, Ingrid; Beck, Daniel; Skinner, Michael K

2018-03-28

A variety of environmental toxicants and factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. Epigenetic alterations in the germline (sperm or egg) are required to transmit transgenerational phenotypes. The current study was designed to investigate the potential role of histones in sperm to help mediate the epigenetic transgenerational inheritance. The agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) were independently used to promote the epigenetic transgenerational inheritance of disease. Purified cauda epididymal sperm were collected from the transgenerational F3 generation control and exposure lineage male rats for histone analysis. A reproducible core of histone H3 retention sites was observed using an H3 chromatin immunoprecipitation (ChIP-Seq) analysis in control lineage sperm. Interestingly, the same core group of H3 retention sites plus additional differential histone retention sites (DHRs) were observed in the F3 generation exposure lineage sperm. Although new histone H3 retention sites were observed, negligible change in histone modification (methylation of H3K27me3) was observed between the control and exposure lineages. Observations demonstrate that in addition to alterations in sperm DNA methylation and ncRNA previously identified, the induction of differential histone retention sites (DHRs) also appear to be involved in environmentally induced epigenetic transgenerational inheritance.

Osteosarcoma inheritance in two families of Scottish deerhounds.

PubMed

Dillberger, John E; McAtee, Sara Ann

2017-01-01

Osteosarcoma is the most common neoplastic disease in Scottish Deerhounds. For Deerhounds, a 2007 population-based study concluded that a single dominant genetic factor largely governed disease risk. For Greyhounds, Rottweilers, and Irish Wolfhounds, a 2013 genome-wide association study found multiple genetic markers in each breed, with each marker only weakly associated with the disease. We obtained from two breeders the pedigrees, age (if alive) or age at death, and osteosarcoma status for two families of Scottish Deerhounds, designated Cohorts K and T. A dog was considered unaffected only if it was osteosarcoma-free and at least 8.5 years old. We analyzed the data in two ways, by assuming either a single recessive genetic factor or a single dominant genetic factor with high penetrance. Cohort K contained 54 evaluable dogs representing 12 litters. Cohort T contained 56 evaluable dogs representing eight litters. Osteosarcoma seemed clearly heritable in both cohorts; however, having a parent with osteosarcoma raised a pup's risk of developing osteosarcoma to 38% for Cohort K but 78% for Cohort T, suggesting the possibility of different genetic risk factors in each cohort. In Cohort K, osteosarcoma inheritance fit well with a single, recessive, autosomal risk factor, although we could not rule out the possibility of a single dominant risk factor with incomplete penetrance. In Cohort T, inheritance could be explained well by a single, dominant, autosomal risk factor but was inconsistent with recessive expression. Inheritance of osteosarcoma in two Scottish Deerhound families could be explained well by a single genetic risk factor residing on an autosome, consistent with a 2007 report. In one family, inheritance was consistent with dominant expression, as previously reported. In the other family, inheritance fit better with recessive expression, although the possibility of a dominant genetic factor influenced by one or more other genetic factors could not be ruled

The evolutionary implications of epigenetic inheritance.

PubMed

Jablonka, Eva

2017-10-06

The Modern Evolutionary Synthesis (MS) forged in the mid-twentieth century was built on a notion of heredity that excluded soft inheritance, the inheritance of the effects of developmental modifications. However, the discovery of molecular mechanisms that generate random and developmentally induced epigenetic variations is leading to a broadening of the notion of biological heredity that has consequences for ideas about evolution. After presenting some old challenges to the MS that were raised, among others, by Karl Popper, I discuss recent research on epigenetic inheritance, which provides experimental and theoretical support for these challenges. There is now good evidence that epigenetic inheritance is ubiquitous and is involved in adaptive evolution and macroevolution. I argue that the many evolutionary consequences of epigenetic inheritance open up new research areas and require the extension of the evolutionary synthesis beyond the current neo-Darwinian model.

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

PubMed Central

Li, Wenzhu; Yi, Jia; Agbu, Pamela; Zhou, Zheng; Kelley, Richard L.; Jia, Songtao

2017-01-01

The fidelity of epigenetic inheritance or, the precision by which epigenetic information is passed along, is an essential parameter for measuring the effectiveness of the process. How the precision of the process is achieved or modulated, however, remains largely elusive. We have performed quantitative measurement of epigenetic fidelity, using position effect variegation (PEV) in Schizosaccharomyces pombe as readout, to explore whether replication perturbation affects nucleosome-mediated epigenetic inheritance. We show that replication stresses, due to either hydroxyurea treatment or various forms of genetic lesions of the replication machinery, reduce the inheritance accuracy of CENP-A/Cnp1 nucleosome positioning within centromere. Mechanistically, we demonstrate that excessive formation of single-stranded DNA, a common molecular abnormality under these conditions, might have correlation with the reduction in fidelity of centromeric chromatin duplication. Furthermore, we show that replication stress broadly changes chromatin structure at various loci in the genome, such as telomere heterochromatin expanding and mating type locus heterochromatin spreading out of the boundaries. Interestingly, the levels of inheritable expanding at sub-telomeric heterochromatin regions are highly variable among independent cell populations. Finally, we show that HU treatment of the multi-cellular organisms C. elegans and D. melanogaster affects epigenetically programmed development and PEV, illustrating the evolutionary conservation of the phenomenon. Replication stress, in addition to its demonstrated role in genetic instability, promotes variable epigenetic instability throughout the epigenome. PMID:28749973

Inherited Retinal Degenerative Clinical Trial Network

DTIC Science & Technology

2009-10-01

ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network

CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING

PubMed Central

HAFLER, BRIAN P.

2017-01-01

Purpose Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. Methods A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Results Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Conclusion Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies. PMID:27753762

Identifying common values among seven health professions: An interprofessional analysis.

PubMed

Grace, Sandra; Innes, Ev; Joffe, Beverly; East, Leah; Coutts, Rosanne; Nancarrow, Susan

2017-05-01

This article reviews the competency frameworks of seven Australian health professions to explore relationships among health professions of similar status as reflected in their competency frameworks and to identify common themes and values across the professions. Frameworks were compared using a constructivist grounded theory approach to identify key themes, against which individual competencies for each profession were mapped and compared. The themes were examined for underlying values and a higher order theoretical framework was developed. In contrast to classical theories of professionalism that foreground differentiation of professions, our study suggests that the professions embrace a common structure and understanding, based on shared underpinning values. We propose a model of two core values that encompass all identified themes: the rights of the client and the capacity of a particular profession to serve the healthcare needs of clients. Interprofessional practice represents the intersection of the rights of the client to receive the best available healthcare and the recognition of the individual contribution of each profession. Recognising that all health professions adhere to a common value base, and exploring professional similarities and differences from that value base, challenges a paradigm that distinguishes professions solely on scope of practice.

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems.

PubMed

Ye, Christine J; Regan, Sarah; Liu, Guo; Alemara, Sarah; Heng, Henry H

2018-01-01

In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer. As the molecular characterization of the causes and effects of aneuploidy progresses, the search for the general mechanism of how aneuploidy contributes to cancer becomes increasingly challenging: since aneuploidy can be linked to diverse molecular pathways (in regards to both cause and effect), the chances of it being cancerous is highly context-dependent, making it more difficult to study than individual molecular mechanisms. When so many genomic and environmental factors can be linked to aneuploidy, and most of them not commonly shared among patients, the practical value of characterizing additional genetic/epigenetic factors contributing to aneuploidy decreases. Based on the fact that cancer typically represents a complex adaptive system, where there is no linear relationship between lower-level agents (such as each individual gene mutation) and emergent properties (such as cancer phenotypes), we call for a new strategy based on the evolutionary mechanism of aneuploidy in cancer, rather than continuous analysis of various individual molecular mechanisms. To illustrate our viewpoint, we have briefly reviewed both the progress and challenges in this field, suggesting the incorporation of an evolutionary-based mechanism to unify diverse molecular mechanisms. To further clarify this rationale, we will discuss some key concepts of the genome theory of cancer evolution, including system inheritance, fuzzy inheritance, and cancer as a newly emergent cellular system. Illustrating how aneuploidy impacts system inheritance, fuzzy inheritance and the emergence of new systems is of great importance. Such synthesis

Identifying strains that contribute to complex diseases through the study of microbial inheritance

PubMed Central

Faith, Jeremiah J.; Colombel, Jean-Frédéric; Gordon, Jeffrey I.

2015-01-01

It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA genes could be used to distinguish the three domains of life on Earth. During the past decade, 16S rDNA sequencing has enabled the now frequent enumeration of bacterial communities that populate the bodies of humans representing different ages, cultural traditions, and health states. A challenge going forward is to quantify the contributions of community members to wellness, disease risk, and disease pathogenesis. Here, we explore a theoretical framework for studies of the inheritance of bacterial strains and discuss the advantages and disadvantages of various study designs for assessing the contribution of strains to complex diseases. PMID:25576328

Developmental origins of epigenetic transgenerational inheritance

PubMed Central

Hanson, Mark A.; Skinner, Michael K.

2016-01-01

Abstract Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective. PMID:27390622

Epigenetic Inheritance: A Contributor to Species Differentiation?

PubMed Central

Boffelli, Dario

2012-01-01

Multiple epigenetic states can be associated with the same genome, and transmitted through the germline for generations, to create the phenomenon of epigenetic inheritance. This form of inheritance is mediated by complex and highly diverse components of the chromosome that associate with DNA, control its transcription, and are inherited alongside it. But, how extensive, and how stable, is the information carried in the germline by the epigenome? Several known examples of epigenetic inheritance demonstrate that it has the ability to create selectable traits, and thus to mediate Darwinian evolution. Here we discuss the possibility that epigenetic inheritance is responsible for some stable characteristics of species, focusing on a recent comparison of the human and chimpanzee methylomes which reveals that somatic methylation states are related to methylation states in the germline. Interpretation of this finding highlights the potential significance of germline epigenetic states, as well as the challenge of investigating a form of inheritance with complex and unfamiliar rules. PMID:22966965

Inherited structure and coupled crust-mantle lithosphere evolution: Numerical models of Central Australia

NASA Astrophysics Data System (ADS)

Heron, Philip J.; Pysklywec, Russell N.

2016-05-01

Continents have a rich tectonic history that have left lasting crustal impressions. In analyzing Central Australian intraplate orogenesis, complex continental features make it difficult to identify the controls of inherited structure. Here the tectonics of two types of inherited structures (e.g., a thermally enhanced or a rheologically strengthened region) are compared in numerical simulations of continental compression with and without "glacial buzzsaw" erosion. We find that although both inherited structures produce deformation in the upper crust that is confined to areas where material contrasts, patterns of deformation in the deep lithosphere differ significantly. Furthermore, our models infer that glacial buzzsaw erosion has little impact at depth. This tectonic isolation of the mantle lithosphere from glacial processes may further assist in the identification of a controlling inherited structure in intraplate orogenesis. Our models are interpreted in the context of Central Australian tectonics (specifically the Petermann and Alice Springs orogenies).

25 CFR 91.9 - Inheritance of improvements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Inheritance of improvements. 91.9 Section 91.9 Indians..., OSAGE RESERVATION, OKLAHOMA § 91.9 Inheritance of improvements. (a) Upon the death of the owner of... of the county courts, State of Oklahoma, and shall be subject to inheritance or bequest in accordance...

Biparental chloroplast inheritance leads to rescue from cytonuclear incompatibility.

PubMed

Barnard-Kubow, Karen B; McCoy, Morgan A; Galloway, Laura F

2017-02-01

Although organelle inheritance is predominantly maternal across animals and plants, biparental chloroplast inheritance has arisen multiple times in the angiosperms. Biparental inheritance has the potential to impact the evolutionary dynamics of cytonuclear incompatibility, interactions between nuclear and organelle genomes that are proposed to be among the earliest types of genetic incompatibility to arise in speciation. We examine the interplay between biparental inheritance and cytonuclear incompatibility in Campanulastrum americanum, a plant species exhibiting both traits. We first determine patterns of chloroplast inheritance in genetically similar and divergent crosses, and then associate inheritance with hybrid survival across multiple generations. There is substantial biparental inheritance in C. americanum. The frequency of biparental inheritance is greater in divergent crosses and in the presence of cytonuclear incompatibility. Biparental inheritance helps to mitigate cytonuclear incompatibility, leading to increased fitness of F 1 hybrids and recovery in the F 2 generation. This study demonstrates the potential for biparental chloroplast inheritance to rescue cytonuclear compatibility, reducing cytonuclear incompatibility's contribution to reproductive isolation and potentially slowing speciation. The efficacy of rescue depended upon the strength of incompatibility, with a greater persistence of weak incompatibilities in later generations. These findings suggest that incompatible plastids may lead to selection for biparental inheritance. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Genetic basis of early-onset, MODY-like diabetes in Japan and features of patients without mutations in the major MODY genes: dominance of maternal inheritance.

PubMed

Yorifuji, Tohru; Higuchi, Shinji; Kawakita, Rie; Hosokawa, Yuki; Aoyama, Takane; Murakami, Akiko; Kawae, Yoshiko; Hatake, Kazue; Nagasaka, Hironori; Tamagawa, Nobuyoshi

2018-06-21

Causative mutations cannot be identified in the majority of Asian patients with suspected maturity-onset diabetes of the young (MODY). To elucidate the genetic basis of Japanese patients with MODY-like diabetes and gain insight into the etiology of patients without mutations in the major MODY genes. 263 Japanese patients with early-onset, nonobese, MODY-like diabetes mellitus referred to Osaka City General Hospital for diagnosis. Mutational analysis of the four major MODY genes (GCK, HNF1A, HNF4A, HNF1B) by Sanger sequencing. Mutation-positive and mutation-negative patients were further analyzed for clinical features. Mutations were identified in 103 (39.2%) patients; 57 mutations in GCK; 29, HNF1A; 7, HNF4A; and 10, HNF1B. Contrary to conventional diagnostic criteria, 18.4% of mutation-positive patients did not have affected parents and 8.2% were in the overweight range (BMI >85 th percentile). HOMA-IR at diagnosis was elevated (>2) in 15 of 66 (22.7%) mutation-positive patients. Compared with mutation-positive patients, mutation-negative patients were significantly older (p = 0.003), and had higher BMI percentile at diagnosis (p = 0.0006). Interestingly, maternal inheritance of diabetes was significantly more common in mutation-negative patients (p = 0.0332) and these patients had significantly higher BMI percentile as compared with mutation-negative patients with paternal inheritance (p = 0.0106). Contrary to the conventional diagnostic criteria, de novo diabetes, overweight, and insulin-resistance are common in Japanese patients with mutation-positive MODY. A significant fraction of mutation-negative patients had features of early-onset type 2 diabetes common in Japanese, and non-Mendelian inheritance needs to be considered for these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pregnancy complications in women with inherited thrombophilia.

PubMed

Weintraub, Adi Y; Sheiner, Eyal; Levy, Amalia; Yerushalmi, Ronit; Mazor, Moshe

2006-06-01

The purpose of this study was to examine whether women with inherited thrombophilia have an increased risk of developing pregnancy complications. All singleton pregnancies with known inherited thrombophilia were compared to those without inherited thrombophilia for deliveries during the years 2000-2002 in a tertiary medical center. Data regarding inherited thrombophilia (International Classification of Disease 9th revision, Clinical Modification code 286.3) were available from the perinatal database in our center. Women lacking prenatal care were excluded from the analysis. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders. Out of 32,763 singleton deliveries that occurred during the study period, 0.2% (n=57) of the women were diagnosed with inherited thrombophilia. Using a multivariate analysis, with backward elimination, the following conditions were significantly associated with inherited thrombophilia: previous fetal losses [odds ratio (OR)=5.5; 95% confidence interval (CI) 2.9-10.3; P<0.001], recurrent abortions (OR=9.5; 95% CI 5.5-16.3; P<0.001), fertility treatments (OR=3.7; 95% CI 1.3-10.6; P=0.014), and intrauterine growth restriction (OR=7.2; 95% CI 3.4-15; P<0.001). Perinatal mortality was significantly higher in women with inherited thrombophilia than in those without known thrombophilia 5.3% (3/57) versus 0.6% (477/32,763) P=0.017. However, inherited thrombophilia was not found to be an independent risk factor for perinatal mortality (OR=3.05; 95% CI 0.90-10.3; P<0.073) in a multivariate analysis with perinatal mortality as the outcome variable, controlling for recurrent abortions, IUGR, and gestational age. Inherited thrombophilia, associated with previous fetal losses, recurrent abortions, fertility treatments, and intrauterine growth restriction, was not an independent risk factor for perinatal mortality.

Frequency and natural history of inherited bone marrow failure syndromes: the Israeli Inherited Bone Marrow Failure Registry.

PubMed

Tamary, Hannah; Nishri, Daniella; Yacobovich, Joanne; Zilber, Rama; Dgany, Orly; Krasnov, Tanya; Aviner, Shraga; Stepensky, Polina; Ravel-Vilk, Shoshana; Bitan, Menachem; Kaplinsky, Chaim; Ben Barak, Ayelet; Elhasid, Ronit; Kapelusnik, Joseph; Koren, Ariel; Levin, Carina; Attias, Dina; Laor, Ruth; Yaniv, Isaac; Rosenberg, Philip S; Alter, Blanche P

2010-08-01

Inherited bone marrow failure syndromes are rare genetic disorders characterized by bone marrow failure, congenital anomalies, and cancer predisposition. Available single disease registries provide reliable information regarding natural history, efficacy and side effects of treatments, and contribute to the discovery of the causative genes. However, these registries could not shed light on the true incidence of the various syndromes. We, therefore, established an Israeli national registry in order to investigate the relative frequency of each of these syndromes and their complications. Patients were registered by their hematologists in all 16 medical centers in Israel. We included patients with Fanconi anemia, severe congenital neutropenia, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, dyskeratosis congenita, Shwachman-Diamond syndrome, and thrombocytopenia with absent radii. One hundred and twenty-seven patients diagnosed between 1966 and 2007 were registered. Fifty-two percent were found to have Fanconi anemia, 17% severe congenital neutropenia, 14% Diamond-Blackfan anemia, 6% congenital amegakaryocytic thrombocytopenia, 5% dyskeratosis congenita, 2% Shwachman-Diamond syndrome, and 2% thrombocytopenia with absent radii. No specific diagnosis was made in only 2 patients. Of the thirty patients (24%) developing severe bone marrow failure, 80% had Fanconi anemia. Seven of 9 patients with leukemia had Fanconi anemia, as did all 6 with solid tumors. Thirty-four patients died from their disease; 25 (74%) had Fanconi anemia and 6 (17%) had severe congenital neutropenia. This is the first comprehensive population-based study evaluating the incidence and complications of the different inherited bone marrow failure syndromes. By far the most common disease was Fanconi anemia, followed by severe congenital neutropenia and Diamond-Blackfan anemia. Fanconi anemia carried the worst prognosis, with severe bone marrow failure and cancer susceptibility

Genetics Home Reference: inherited thyroxine-binding globulin deficiency

MedlinePlus

... Health Conditions Inherited thyroxine-binding globulin deficiency Inherited thyroxine-binding globulin deficiency Printable PDF Open All Close ... to view the expand/collapse boxes. Description Inherited thyroxine-binding globulin deficiency is a genetic condition that ...

Vector platforms for gene therapy of inherited retinopathies

PubMed Central

Trapani, Ivana; Puppo, Agostina; Auricchio, Alberto

2014-01-01

Inherited retinopathies (IR) are common untreatable blinding conditions. Most of them are inherited as monogenic disorders, due to mutations in genes expressed in retinal photoreceptors (PR) and in retinal pigment epithelium (RPE). The retina’s compatibility with gene transfer has made transduction of different retinal cell layers in small and large animal models via viral and non-viral vectors possible. The ongoing identification of novel viruses as well as modifications of existing ones based either on rational design or directed evolution have generated vector variants with improved transduction properties. Dozens of promising proofs of concept have been obtained in IR animal models with both viral and non-viral vectors, and some of them have been relayed to clinical trials. To date, recombinant vectors based on the adeno-associated virus (AAV) represent the most promising tool for retinal gene therapy, given their ability to efficiently deliver therapeutic genes to both PR and RPE and their excellent safety and efficacy profiles in humans. However, AAVs’ limited cargo capacity has prevented application of the viral vector to treatments requiring transfer of genes with a coding sequence larger than 5 kb. Vectors with larger capacity, i.e. nanoparticles, adenoviral and lentiviral vectors are being exploited for gene transfer to the retina in animal models and, more recently, in humans. This review focuses on the available platforms for retinal gene therapy to fight inherited blindness, highlights their main strengths and examines the efforts to overcome some of their limitations. PMID:25124745

A common co-morbidity modulates disease expression and treatment efficacy in inherited cardiac sodium channelopathy.

PubMed

Rivaud, Mathilde R; Jansen, John A; Postema, Pieter G; Nannenberg, Eline A; Mizusawa, Yuka; van der Nagel, Roel; Wolswinkel, Rianne; van der Made, Ingeborg; Marchal, Gerard A; Rajamani, Sridharan; Belardinelli, Luiz; van Tintelen, J Peter; Tanck, Michael W T; van der Wal, Allard C; de Bakker, Jacques M T; van Rijen, Harold V; Creemers, Esther E; Wilde, Arthur A M; van den Berg, Maarten P; van Veen, Toon A B; Bezzina, Connie R; Remme, Carol Ann

2018-04-27

Management of patients with inherited cardiac ion channelopathy is hindered by variability in disease severity and sudden cardiac death (SCD) risk. Here, we investigated the modulatory role of hypertrophy on arrhythmia and SCD risk in sodium channelopathy. Follow-up data was collected from 164 individuals positive for the SCN5A-1795insD founder mutation and 247 mutation-negative relatives. A total of 38 (obligate) mutation-positive patients died suddenly or suffered life-threatening ventricular arrhythmia. Of these, 18 were aged >40 years, a high proportion of which had a clinical diagnosis of hypertension and/or cardiac hypertrophy. While pacemaker implantation was highly protective in preventing bradycardia-related SCD in young mutation-positive patients, seven of them aged >40 experienced life-threatening arrhythmic events despite pacemaker treatment. Of these, six had a diagnosis of hypertension/hypertrophy, pointing to a modulatory role of this co-morbidity. Induction of hypertrophy in adult mice carrying the homologous mutation (Scn5a1798insD/+) caused SCD and excessive conduction disturbances, confirming a modulatory effect of hypertrophy in the setting of the mutation. The deleterious effects of the interaction between hypertrophy and the mutation were prevented by genetically impairing the pro-hypertrophic response and by pharmacological inhibition of the enhanced late sodium current associated with the mutation. This study provides the first evidence for a modulatory effect of co-existing cardiac hypertrophy on arrhythmia risk and treatment efficacy in inherited sodium channelopathy. Our findings emphasize the need for continued assessment and rigorous treatment of this co-morbidity in SCN5A mutation-positive individuals.

The ethical framework for performing research with rare inherited neurometabolic disease patients.

PubMed

Giannuzzi, Viviana; Devlieger, Hugo; Margari, Lucia; Odlind, Viveca Lena; Ragab, Lamis; Bellettato, Cinzia Maria; D'Avanzo, Francesca; Lampe, Christina; Cassis, Linda; Cortès-Saladelafont, Elisenda; Cazorla, Ángels Garcia; Barić, Ivo; Cvitanović-Šojat, Ljerka; Fumić, Ksenija; Dali, Christine I; Bartoloni, Franco; Bonifazi, Fedele; Scarpa, Maurizio; Ceci, Adriana

2017-03-01

The need for performing clinical trials to develop well-studied and appropriate medicines for inherited neurometabolic disease patients faces ethical concerns mainly raising from four aspects: the diseases are rare; include young and very young patients; the neurological impairment may compromise the capability to provide 'consent'; and the genetic nature of the disease leads to further ethical implications. This work is intended to identify the ethical provisions applicable to clinical research involving these patients and to evaluate if these cover the ethical issues. Three searches have been performed on the European regulatory/legal framework, the literature and European Union-funded projects. The European legal framework offers a number of ethical provisions ruling the clinical research on paediatric, rare, inherited diseases with neurological symptoms. In the literature, relevant publications deal with informed consent, newborn genetic screenings, gene therapy and rights/interests of research participants. Additional information raised from European projects on sharing patients' data from different countries, the need to fill the gap of the regulatory framework and to improve information to stakeholders and patients/families. Several recommendations and guidelines on ethical aspects are applicable to the inherited neurometabolic disease research in Europe, even though they suffer from the lack of a common ethical approach. What is Known: • When planning and conducting clinical trials, sponsors and researchers know that clinical trials are to be performed according to well-established ethical rules, and patients should be aware about their rights. • In the cases of paediatric patients, vulnerable patients unable to provide consent, genetic diseases' further rules apply. What is New: • This work discusses which ethical rules apply to ensure protection of patient's rights if all the above-mentioned features coexist. • This work shows available data and

A Computer-Based Instrument That Identifies Common Science Misconceptions

ERIC Educational Resources Information Center

Larrabee, Timothy G.; Stein, Mary; Barman, Charles

2006-01-01

This article describes the rationale for and development of a computer-based instrument that helps identify commonly held science misconceptions. The instrument, known as the Science Beliefs Test, is a 47-item instrument that targets topics in chemistry, physics, biology, earth science, and astronomy. The use of an online data collection system…

Inheritance of flower color in periwinkle: orange-red corolla and white eye.

PubMed

Sreevalli, Y; Kulkarni, R N; Baskaran, K

2002-01-01

The commonly found flower colors in periwinkle (Catharanthus roseus)--pink, white, red-eyed, and pale pink center--are reported to be governed by the epistatic interaction between four genes--A, R, W, and I. The mode of inheritance of an uncommon flower color, orange-red corolla and white eye, was studied by crossing an accession possessing this corolla color with a white flowered variety (Nirmal). The phenotype of the F(1) plants and segregation data of F(2) and backcross generations suggested the involvement of two more interacting and independently inherited genes, one (proposed symbol E) determining the presence or absence of red eye and another (proposed symbol O) determining orange-red corolla.

Exploring digenic inheritance in arrhythmogenic cardiomyopathy.

PubMed

König, Eva; Volpato, Claudia Béu; Motta, Benedetta Maria; Blankenburg, Hagen; Picard, Anne; Pramstaller, Peter; Casella, Michela; Rauhe, Werner; Pompilio, Giulio; Meraviglia, Viviana; Domingues, Francisco S; Sommariva, Elena; Rossini, Alessandra

2017-12-08

Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors. We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes. We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein's only serine kinase domain. In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model.

Inheritance of tristyly in Oxalis tuberosa (Oxalidaceae).

PubMed

Trognitz, B R; Hermann, M

2001-05-01

Frequencies of floral morphs in progenies obtained from a complete set of diallelic crosses among three accessions of tristylous, octoploid oca (Oxalis tuberosa) were used for a Mendelian analysis of floral morph inheritance. The frequencies observed had the best fit to a model of tetrasomic inheritance with two diallelic factors, S, s and M, m, with S being epistatic over M. No explanation could be found for the unexpected formation of a small percentage of short-styled individuals in crosses between the mid-styled and the long-styled parent. For the acceptance of models of disomic and octosomic inheritance several additional assumptions would have to be made and therefore these modes of inheritance are less likely. Dosage-dependent inheritance of floral morph was rejected. Only a small frequency (36%) of the cross progenies flowered, in contrast to the greater propensity for flowering of O. tuberosa accessions held at gene banks.

Disentangling prenatal and inherited influences in humans with an experimental design.

PubMed

Rice, Frances; Harold, Gordon T; Boivin, Jacky; Hay, Dale F; van den Bree, Marianne; Thapar, Anita

2009-02-17

Exposure to adversity in utero at a sensitive period of development can bring about physiological, structural, and metabolic changes in the fetus that affect later development and behavior. However, the link between prenatal environment and offspring outcomes could also arise and confound because of the relation between maternal and offspring genomes. As human studies cannot randomly assign offspring to prenatal conditions, it is difficult to test whether in utero events have true causal effects on offspring outcomes. We used an unusual approach to overcome this difficulty whereby pregnant mothers are either biologically unrelated or related to their child as a result of in vitro fertilization (IVF). In this sample, prenatal smoking reduces offspring birth weight in both unrelated and related offspring, consistent with effects arising through prenatal mechanisms independent of the relation between the maternal and offspring genomes. In contrast, the association between prenatal smoking and offspring antisocial behavior depended on inherited factors because association was only present in related mothers and offspring. The results demonstrate that this unusual prenatal cross-fostering design is feasible and informative for disentangling inherited and prenatal effects on human health and behavior. Disentangling these different effects is invaluable for pinpointing markers of prenatal adversity that have a causal effect on offspring outcomes. The origins of behavior and many common complex disorders may begin in early life, therefore this experimental design could pave the way for identifying prenatal factors that affect behavior in future generations.

Clinical management of a child with Prader-Willi Syndrome from maternal uniparental disomy (UPD) genetic inheritance.

PubMed

Bellon-Harn, Monica L

2005-01-01

Prader-Willi Syndrome (PWS) is reported in 1 in 10,000-15,000 individuals. Unfortunately, many cases are missed due to clinicians' lack of familiarity with the syndrome as well as clinical and laboratory diagnostic criteria. Although common clinical characteristics are reported, variety exists in the nature and severity of dysfunction associated with PWS. Case studies can provide information to understand relationships between phenotypic characteristics and genetic inheritance, which can in turn lead to effective clinical management. The purpose of this case study was to describe the characteristics of a child with PWS due to maternal uniparental disomy inheritance pattern and to describe clinical management and treatment outcomes. The reader will obtain information about: (1) the genetic inheritance patterns and clinical characteristics of Prader-Willi Syndrome, (2) genotypic/phenotypic relationships specific to Prader-Willi Syndrome, and (3) clinical implications, management, and outcomes in a case description of a child with PWS due to maternal uniparental disomy inheritance pattern.

Common Marker Genes Identified from Various Sample Types for Systemic Lupus Erythematosus.

PubMed

Bing, Peng-Fei; Xia, Wei; Wang, Lan; Zhang, Yong-Hong; Lei, Shu-Feng; Deng, Fei-Yan

2016-01-01

Systemic lupus erythematosus (SLE) is a complex auto-immune disease. Gene expression studies have been conducted to identify SLE-related genes in various types of samples. It is unknown whether there are common marker genes significant for SLE but independent of sample types, which may have potentials for follow-up translational research. The aim of this study is to identify common marker genes across various sample types for SLE. Based on four public microarray gene expression datasets for SLE covering three representative types of blood-born samples (monocyte; peripheral blood mononuclear cell, PBMC; whole blood), we utilized three statistics (fold-change, FC; t-test p value; false discovery rate adjusted p value) to scrutinize genes simultaneously regulated with SLE across various sample types. For common marker genes, we conducted the Gene Ontology enrichment analysis and Protein-Protein Interaction analysis to gain insights into their functions. We identified 10 common marker genes associated with SLE (IFI6, IFI27, IFI44L, OAS1, OAS2, EIF2AK2, PLSCR1, STAT1, RNASE2, and GSTO1). Significant up-regulation of IFI6, IFI27, and IFI44L with SLE was observed in all the studied sample types, though the FC was most striking in monocyte, compared with PBMC and whole blood (8.82-251.66 vs. 3.73-74.05 vs. 1.19-1.87). Eight of the above 10 genes, except RNASE2 and GSTO1, interact with each other and with known SLE susceptibility genes, participate in immune response, RNA and protein catabolism, and cell death. Our data suggest that there exist common marker genes across various sample types for SLE. The 10 common marker genes, identified herein, deserve follow-up studies to dissert their potentials as diagnostic or therapeutic markers to predict SLE or treatment response.

Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families.

PubMed

Leppa, Virpi M; Kravitz, Stephanie N; Martin, Christa Lese; Andrieux, Joris; Le Caignec, Cedric; Martin-Coignard, Dominique; DyBuncio, Christina; Sanders, Stephan J; Lowe, Jennifer K; Cantor, Rita M; Geschwind, Daniel H

2016-09-01

Rare mutations, including copy-number variants (CNVs), contribute significantly to autism spectrum disorder (ASD) risk. Although their importance has been established in families with only one affected child (simplex families), the contribution of both de novo and inherited CNVs to ASD in families with multiple affected individuals (multiplex families) is less well understood. We analyzed 1,532 families from the Autism Genetic Resource Exchange (AGRE) to assess the impact of de novo and rare CNVs on ASD risk in multiplex families. We observed a higher burden of large, rare CNVs, including inherited events, in individuals with ASD than in their unaffected siblings (odds ratio [OR] = 1.7), but the rate of de novo events was significantly lower than in simplex families. In previously characterized ASD risk loci, we identified 49 CNVs, comprising 24 inherited events, 19 de novo events, and 6 events of unknown inheritance, a significant enrichment in affected versus control individuals (OR = 3.3). In 21 of the 30 families (71%) in whom at least one affected sibling harbored an established ASD major risk CNV, including five families harboring inherited CNVs, the CNV was not shared by all affected siblings, indicating that other risk factors are contributing. We also identified a rare risk locus for ASD and language delay at chromosomal region 2q24 (implicating NR4A2) and another lower-penetrance locus involving inherited deletions and duplications of WWOX. The genetic architecture in multiplex families differs from that in simplex families and is complex, warranting more complete genetic characterization of larger multiplex ASD cohorts. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

77 FR 14700 - Streamlining Inherited Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-13

... contains notices to the public of #0;the proposed issuance of rules and regulations. The purpose of these... X [Docket No. CFPB-2011-0039] Streamlining Inherited Regulations AGENCY: Bureau of Consumer... the public for streamlining regulations it recently inherited from other Federal agencies (the...

Role of structural inheritance on present-day deformation in intraplate domains

NASA Astrophysics Data System (ADS)

Tarayoun, A.; Mazzotti, S.; Gueydan, F.

2017-12-01

Understanding the role of structural inheritance on present day surface deformation is a key element for better characterizing the dynamism of intraplate earthquakes. Current deformation and seismicity are poorly understood phenomenon in intra-continental domains. A commonly used hypothesis, based on observations, suggests that intraplate deformation is related to the reactivation of large tectonic paleo-structures, which can act as locally weakened domains. The objective of our study is to quantify the impact of these weakened areas on present-day strain localizations and rates. We combine GPS observations and numerical modeling to analyze the role of structural inheritance on strain rates, with specific observations along the St. Lawrence Valley of eastern Canada. We processed 143 GPS stations from five different networks, in particular one dense campaign network situated along a recognized major normal faults system of the Iapetus paleo-rift, in order to accurately determine the GPS velocities and strain rates. Results of strain rates show magnitude varying from 1.5x10-10 to 6.8x10-9 yr-1 in the St Lawrence valley. Weakened area strain rates are up to one order of magnitude higher than surrounding areas. We compare strain rates inferred from GPS and the new postglacial rebound model. We found that GPS signal is one order of magnitude higher in the weakened zone, which is likely due to structural inheritance. The numerical modeling investigates the steady-state deformation of the continental lithosphere with presence of a weak area. Our new approach integrates ductile structural inheritance using a weakening coefficient that decreases the lithosphere strength at different depths. This allows studying crustal strain rates mainly as a function of rheological contrast and geometry of the weakened domains. Comparison between model predictions and observed GPS strain rates will allow us to investigate the respective role of crustal and mantle tectonic inheritance.

Inherited platelet disorders: toward DNA-based diagnosis

PubMed Central

Lentaigne, Claire; Freson, Kathleen; Laffan, Michael A.; Turro, Ernest

2016-01-01

Variations in platelet number, volume, and function are largely genetically controlled, and many loci associated with platelet traits have been identified by genome-wide association studies (GWASs).1 The genome also contains a large number of rare variants, of which a tiny fraction underlies the inherited diseases of humans. Research over the last 3 decades has led to the discovery of 51 genes harboring variants responsible for inherited platelet disorders (IPDs). However, the majority of patients with an IPD still do not receive a molecular diagnosis. Alongside the scientific interest, molecular or genetic diagnosis is important for patients. There is increasing recognition that a number of IPDs are associated with severe pathologies, including an increased risk of malignancy, and a definitive diagnosis can inform prognosis and care. In this review, we give an overview of these disorders grouped according to their effect on platelet biology and their clinical characteristics. We also discuss the challenge of identifying candidate genes and causal variants therein, how IPDs have been historically diagnosed, and how this is changing with the introduction of high-throughput sequencing. Finally, we describe how integration of large genomic, epigenomic, and phenotypic datasets, including whole genome sequencing data, GWASs, epigenomic profiling, protein–protein interaction networks, and standardized clinical phenotype coding, will drive the discovery of novel mechanisms of disease in the near future to improve patient diagnosis and management. PMID:27095789

Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies.

PubMed

Lee, Kristy; Garg, Seema

2015-04-01

Inherited eye disorders are a significant cause of vision loss. Genetic testing can be particularly helpful for patients with inherited retinal dystrophies because of genetic heterogeneity and overlapping phenotypes. The need to identify a molecular diagnosis for retinal dystrophies is particularly important in the era of developing novel gene therapy-based treatments, such as the RPE65 gene-based clinical trials and others on the horizon, as well as recent advances in reproductive options. The introduction of massively parallel sequencing technologies has significantly advanced the identification of novel gene candidates and has expanded the landscape of genetic testing. In a relatively short time clinical medicine has progressed from limited testing options to a plethora of choices ranging from single-gene testing to whole-exome sequencing. This article outlines currently available genetic testing and factors to consider when selecting appropriate testing for patients with inherited retinal dystrophies.

Bi-parentally inherited species-specific markers identify hybridization between rainbow trout and cutthroat trout subspecies

USGS Publications Warehouse

Ostberg, C.O.; Rodriguez, R.J.

2004-01-01

Eight polymerase chain reaction primer sets amplifying bi-parentally inherited species-specific markers were developed that differentiate between rainbow trout (Oncorhynchus mykiss) and various cutthroat trout (O. clarki) subspecies. The primers were tested within known F1 and first generation hybrid backcrosses and were shown to amplify codominantly within hybrids. Heterozygous individuals also amplified a slower migrating band that was a heteroduplex, caused by the annealing of polymerase chain reaction products from both species. These primer sets have numerous advantages for native cutthroat trout conservation including statistical genetic analyses of known crosses and simple hybrid identification.

Whole-Exome Sequencing Identifies Novel Variants for Tooth Agenesis.

PubMed

Dinckan, N; Du, R; Petty, L E; Coban-Akdemir, Z; Jhangiani, S N; Paine, I; Baugh, E H; Erdem, A P; Kayserili, H; Doddapaneni, H; Hu, J; Muzny, D M; Boerwinkle, E; Gibbs, R A; Lupski, J R; Uyguner, Z O; Below, J E; Letra, A

2018-01-01

Tooth agenesis is a common craniofacial abnormality in humans and represents failure to develop 1 or more permanent teeth. Tooth agenesis is complex, and variations in about a dozen genes have been reported as contributing to the etiology. Here, we combined whole-exome sequencing, array-based genotyping, and linkage analysis to identify putative pathogenic variants in candidate disease genes for tooth agenesis in 10 multiplex Turkish families. Novel homozygous and heterozygous variants in LRP6, DKK1, LAMA3, and COL17A1 genes, as well as known variants in WNT10A, were identified as likely pathogenic in isolated tooth agenesis. Novel variants in KREMEN1 were identified as likely pathogenic in 2 families with suspected syndromic tooth agenesis. Variants in more than 1 gene were identified segregating with tooth agenesis in 2 families, suggesting oligogenic inheritance. Structural modeling of missense variants suggests deleterious effects to the encoded proteins. Functional analysis of an indel variant (c.3607+3_6del) in LRP6 suggested that the predicted resulting mRNA is subject to nonsense-mediated decay. Our results support a major role for WNT pathways genes in the etiology of tooth agenesis while revealing new candidate genes. Moreover, oligogenic cosegregation was suggestive for complex inheritance and potentially complex gene product interactions during development, contributing to improved understanding of the genetic etiology of familial tooth agenesis.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes.

PubMed

Christie, Joshua R; Beekman, Madeleine

2017-03-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes-specifically their organization into host cells and their uniparental (maternal) inheritance-enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller's ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes-despite their asexual mode of reproduction-can readily undergo adaptive evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Emulating multiple inheritance in Fortran 2003/2008

DOE PAGES

Morris, Karla

2015-01-24

Although the high-performance computing (HPC) community increasingly embraces object-oriented programming (OOP), most HPC OOP projects employ the C++ programming language. Until recently, Fortran programmers interested in mining the benefits of OOP had to emulate OOP in Fortran 90/95. The advent of widespread compiler support for Fortran 2003 now facilitates explicitly constructing object-oriented class hierarchies via inheritance and leveraging related class behaviors such as dynamic polymorphism. Although C++ allows a class to inherit from multiple parent classes, Fortran and several other OOP languages restrict or prohibit explicit multiple inheritance relationships in order to circumvent several pitfalls associated with them. Nonetheless, whatmore » appears as an intrinsic feature in one language can be modeled as a user-constructed design pattern in another language. The present paper demonstrates how to apply the facade structural design pattern to support a multiple inheritance class relationship in Fortran 2003. As a result, the design unleashes the power of the associated class relationships for modeling complicated data structures yet avoids the ambiguities that plague some multiple inheritance scenarios.« less

Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease

PubMed Central

Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I.; Skinner, Michael K.

2012-01-01

The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology. PMID:22570695

[Gene therapy for inherited retinal dystrophies].

PubMed

Côco, Monique; Han, Sang Won; Sallum, Juliana Maria Ferraz

2009-01-01

The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these conditions and the patients can expect a progressive loss of vision. Accurate genetic counseling and support for rehabilitation are indicated. Research into the molecular and genetic basis of disease is continually expanding and improving the prospects for rational treatments. In this way, gene therapy, defined as the introduction of exogenous genetic material into human cells for therapeutic purposes, may ultimately offer the greatest treatment for the inherited retinal dystrophies. The eye is an attractive target for gene therapy because of its accessibility, immune privilege and translucent media. A number of retinal diseases affecting the eye have known gene defects. Besides, there is a well characterized animal model for many of these conditions. Proposals for clinical trials of gene therapy for inherited retinal degenerations owing to defects in the gene RPE65, have recently received ethical approval and the obtained preliminary results brought large prospects in the improvement on patient's quality of life.

Translating Mendelian and complex inheritance of Alzheimer's disease genes for predicting unique personal genome variants

PubMed Central

Regan, Kelly; Wang, Kanix; Doughty, Emily; Li, Haiquan; Li, Jianrong; Lee, Younghee; Kann, Maricel G

2012-01-01

Objective Although trait-associated genes identified as complex versus single-gene inheritance differ substantially in odds ratio, the authors nonetheless posit that their mechanistic concordance can reveal fundamental properties of the genetic architecture, allowing the automated interpretation of unique polymorphisms within a personal genome. Materials and methods An analytical method, SPADE-gen, spanning three biological scales was developed to demonstrate the mechanistic concordance between Mendelian and complex inheritance of Alzheimer's disease (AD) genes: biological functions (BP), protein interaction modeling, and protein domain implicated in the disease-associated polymorphism. Results Among Gene Ontology (GO) biological processes (BP) enriched at a false detection rate <5% in 15 AD genes of Mendelian inheritance (Online Mendelian Inheritance in Man) and independently in those of complex inheritance (25 host genes of intragenic AD single-nucleotide polymorphisms confirmed in genome-wide association studies), 16 overlapped (empirical p=0.007) and 45 were similar (empirical p<0.009; information theory). SPAN network modeling extended the canonical pathway of AD (KEGG) with 26 new protein interactions (empirical p<0.0001). Discussion The study prioritized new AD-associated biological mechanisms and focused the analysis on previously unreported interactions associated with the biological processes of polymorphisms that affect specific protein domains within characterized AD genes and their direct interactors using (1) concordant GO-BP and (2) domain interactions within STRING protein–protein interactions corresponding to the genomic location of the AD polymorphism (eg, EPHA1, APOE, and CD2AP). Conclusion These results are in line with unique-event polymorphism theory, indicating how disease-associated polymorphisms of Mendelian or complex inheritance relate genetically to those observed as ‘unique personal variants’. They also provide insight for

Inheritance pattern of lip prints among Malay population: A pilot study.

PubMed

George, Renjith; Nora Afandi, Nurulain Syafinaz Binti; Zainal Abidin, Siti Nur Hayati Binti; Binti Ishak, Nur Ismawani; Soe, Htoo Htoo Kyaw; Ismail, Abdul Rashid Hj

2016-04-01

We assessed the resemblance of lip print patterns between parents and biological offspring in families of 31 Malay students as well as the distribution of different types of lip print in the study group. Only a few studies have successfully established the inheritance pattern of lip prints. Such studies can be population specific and need to be conducted in various populations. No such study have been conducted in Malay population in Malaysia, according to our knowledge. Present study was carried out to ascertain whether there is any inherence pattern in lip prints and thereby to investigate the potential role of lip prints in personal identification. We found 58.06% resemblance of lip print patterns between the parents and their biological offspring in our study. The influence of heredity in lip print pattern is still a new concept and there is lack of concrete evidence. The data from our study shows that there is potential influence of inheritance in the lip print patterns among the family members. Further researches involving larger samples size are suggested to derive more reliable and accurate results. The most common lip print pattern among the study group is type I (29.84%) followed by type II (23.12%), type III (22.45%), type I' (13.44%), type IV (9.54%) and type V (1.61%). Racial variations in lip print patterns and their prevalence may serve as an aid in forensic identification and crime scene investigation. The results of this pilot study will help in establishing guidelines for future researches on lip print analysis in Malaysia. Lip print patterns are unique and individualistic. However, there are some similarities in basic patterns of lip prints between family members which may be attributed to influence of inheritance. 1. To determine the inheritance pattern of lip prints among Malay family members of the student. 2. To identify the distribution of different types of lip prints among Malay population. and Observational pilot study. Lip prints of 124

Methodological issues in genetic association studies of inherited thrombophilia: original report of recent practice.

PubMed

Simundic, Ana-Maria; Nikolac, Nora; Topic, Elizabeta

2009-01-01

The aims of this article are to evaluate the methodological quality of genetic association studies on the inherited thrombophilia published during 2003 to 2005, to identify the most common mistakes made by authors of those studies, and to examine if overall quality of the article correlates with the quality of the journal. Articles were evaluated by 2 independent reviewers using the checklist of 16 items. A total of 58 eligible studies were identified. Average total score was 7.59 +/- 1.96. Total article score did not correlate with the journal impact factor (r = 0.3971; 95% confidence interval [CI], 0.1547-0.5944, P = .002). Total score did not differ across years (P = .624). Finally, it is concluded that methodological quality of genetic association studies is not optimal, and it does not depend on the quality of the journal. Journals should adopt methodological criteria for reporting the genetic association studies, and editors should encourage authors to strictly adhere to those criteria.

26 CFR 1.102-1 - Gifts and inheritances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Gifts and inheritances. 1.102-1 Section 1.102-1...) INCOME TAXES (CONTINUED) Items Specifically Excluded from Gross Income § 1.102-1 Gifts and inheritances... inheritances. The income from any property received as a gift, or under a will or statute of descent and...

Inherited disorders of voltage-gated sodium channels

PubMed Central

George, Alfred L.

2005-01-01

A variety of inherited human disorders affecting skeletal muscle contraction, heart rhythm, and nervous system function have been traced to mutations in genes encoding voltage-gated sodium channels. Clinical severity among these conditions ranges from mild or even latent disease to life-threatening or incapacitating conditions. The sodium channelopathies were among the first recognized ion channel diseases and continue to attract widespread clinical and scientific interest. An expanding knowledge base has substantially advanced our understanding of structure-function and genotype-phenotype relationships for voltage-gated sodium channels and provided new insights into the pathophysiological basis for common diseases such as cardiac arrhythmias and epilepsy. PMID:16075039

Panel-based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns.

PubMed

Riera, Marina; Wert, Ana; Nieto, Isabel; Pomares, Esther

2017-11-01

Microphthalmia and anophthalmia (MA) are congenital eye abnormalities that show an extremely high clinical and genetic complexity. In this study, we evaluated the implementation of whole exome sequencing (WES) for the genetic analysis of MA patients. This approach was used to investigate three unrelated families in which previous single-gene analyses failed to identify the molecular cause. A total of 47 genes previously associated with nonsyndromic MA were included in our panel. WES was performed in one affected patient from each family using the AmpliSeq TM Exome technology and the Ion Proton TM platform. A novel heterozygous OTX2 missense mutation was identified in a patient showing bilateral anophthalmia who inherited the variant from a parent who was a carrier, but showed no sign of the condition. We also describe a new PAX6 missense variant in an autosomal-dominant pedigree affected by mild bilateral microphthalmia showing high intrafamiliar variability, with germline mosaicism determined to be the most plausible molecular cause of the disease. Finally, a heterozygous missense mutation in RBP4 was found to be responsible in an isolated case of bilateral complex microphthalmia. This study highlights that panel-based WES is a reliable and effective strategy for the genetic diagnosis of MA. Furthermore, using this technique, the mutational spectrum of these diseases was broadened, with novel variants identified in each of the OTX2, PAX6, and RBP4 genes. Moreover, we report new cases of reduced penetrance, mosaicism, and variable phenotypic expressivity associated with MA, further demonstrating the heterogeneity of such disorders. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Legal Portion in Russian Inheritance Law

ERIC Educational Resources Information Center

Inshina, Roza; Murzalimova, Lyudmila

2013-01-01

In this paper the authors describe the right to inherit as one of the basic human rights guaranteed by the Constitution of the Russian Federation. The state has set rules according to which after a person's death, his or her property is inherited by other persons. The Russian civil legislation establishes the institution of legal portions that is…

The role of inheritance in structuring hyperextended rift systems

NASA Astrophysics Data System (ADS)

Manatschal, Gianreto; Lavier, Luc; Chenin, Pauline

2015-04-01

A long-standing question in Earth Sciences is related to the importance of inheritance in controlling tectonic processes. In contrast to physical processes that are generally applicable, assessing the role of inheritance suffers from two major problems: firstly, it is difficult to appraise without having insights into the history of a geological system; and secondly all inherited features are not reactivated during subsequent deformation phases. Therefore, the aim of our presentation is to give some conceptual framework about how inheritance may control the architecture and evolution of hyperextended rift systems. We use the term inheritance to refer to the difference between an "ideal" layer-cake type lithosphere and a "real" lithosphere containing heterogeneities and we define 3 types of inheritance, namely structural, compositional and thermal inheritance. Moreover, we assume that the evolution of hyperextended rift systems reflects the interplay between their inheritance (innate/"genetic code") and the physical processes at play (acquired/external factors). Thus, by observing the architecture and evolution of hyperextended rift systems and integrating the physical processes, one my get hints on what may have been the original inheritance of a system. Using this approach, we focus on 3 well-studied rift systems that are the Alpine Tethys, Pyrenean-Bay of Biscay and Iberia-Newfoundland rift systems. For the studied examples we can show that: 1) strain localization on a local scale and during early stages of rifting is controlled by inherited structures and weaknesses 2) the architecture of the necking zone seems to be influenced by the distribution and importance of ductile layers during decoupled deformation and is consequently controlled by the thermal structure and/or the inherited composition of the curst 3) the location of breakup in the 3 examples is not significantly controlled by the inherited structures 4) inherited mantle composition and rift

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes

PubMed Central

Christie, Joshua R.; Beekman, Madeleine

2017-01-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution. PMID:28025277

Neuromuscular imaging in inherited muscle diseases

PubMed Central

Kley, Rudolf A.; Fischer, Dirk

2010-01-01

Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. PMID:20422195

Occurrence of plastids in the sperm cells of Caprifoliaceae: biparental plastid inheritance in angiosperms is unilaterally derived from maternal inheritance.

PubMed

Hu, Yingchun; Zhang, Quan; Rao, Guangyuan; Sodmergen

2008-06-01

It is widely held that organelles inherit from the maternal lineage. However, the plastid genome in quite a few angiosperms appears to be biparentally transmitted. It is unclear how and why biparental inheritance of the genome became activated. Here, we detected widespread occurrence of plastids in the sperm cells (a cellular prerequisite for biparental inheritance) of traditional Caprifoliaceae. Of the 12 genera sampled, the sperm cells of Abelia, Dipelta, Heptacodium, Kolkwitzia, Leycesteria, Linnaea, Lonicera, Symphoricarpos, Triosteum and Weigela possessed inheritable plastids. The other genera, Sambucus and Viburnum, lacked plastids in sperm cells. Interestingly, such exclusion of plastids in the sperm cells of some Caprifoliaceae appeared to be associated with the divergence of Dipsacales phylogeny. Closer examination of Weigela florida revealed that both plastids and plastid DNA were highly duplicated in the generative cells. This implies that the appearance of plastids in sperm cells involved cellular mechanisms. Because such mechanisms must enhance the strength of plastid transmission through the paternal lineage and appear ubiquitous in species exhibiting biparental or potential biparental plastid inheritance, we presume that biparental plastid genetics may be a derived trait in angiosperms. This is consistent with our extended phylogenetic analysis using species with recently discovered modes of potential plastid inheritance. The results show that basal and early angiosperms have maternal plastid transmission, whereas all potential biparental transmission occurs at terminal branches of the tree. Thus, unlike previous studies, we suggest that biparental plastid inheritance in angiosperms was unilaterally converted from the maternal transmission mode during late angiosperm evolution.

Selection against Heteroplasmy Explains the Evolution of Uniparental Inheritance of Mitochondria

PubMed Central

Christie, Joshua R.; Schaerf, Timothy M.; Beekman, Madeleine

2015-01-01

Why are mitochondria almost always inherited from one parent during sexual reproduction? Current explanations for this evolutionary mystery include conflict avoidance between the nuclear and mitochondrial genomes, clearing of deleterious mutations, and optimization of mitochondrial-nuclear coadaptation. Mathematical models, however, fail to show that uniparental inheritance can replace biparental inheritance under any existing hypothesis. Recent empirical evidence indicates that mixing two different but normal mitochondrial haplotypes within a cell (heteroplasmy) can cause cell and organism dysfunction. Using a mathematical model, we test if selection against heteroplasmy can lead to the evolution of uniparental inheritance. When we assume selection against heteroplasmy and mutations are neither advantageous nor deleterious (neutral mutations), uniparental inheritance replaces biparental inheritance for all tested parameter values. When heteroplasmy involves mutations that are advantageous or deleterious (non-neutral mutations), uniparental inheritance can still replace biparental inheritance. We show that uniparental inheritance can evolve with or without pre-existing mating types. Finally, we show that selection against heteroplasmy can explain why some organisms deviate from strict uniparental inheritance. Thus, we suggest that selection against heteroplasmy explains the evolution of uniparental inheritance. PMID:25880558

Identifying Genetic Hotspots by Mapping Molecular Diversity of Widespread Trees: When Commonness Matters.

PubMed

Souto, Cintia P; Mathiasen, Paula; Acosta, María Cristina; Quiroga, María Paula; Vidal-Russell, Romina; Echeverría, Cristian; Premoli, Andrea C

2015-01-01

Conservation planning requires setting priorities at the same spatial scale at which decision-making processes are undertaken considering all levels of biodiversity, but current methods for identifying biodiversity hotspots ignore its genetic component. We developed a fine-scale approach based on the definition of genetic hotspots, which have high genetic diversity and unique variants that represent their evolutionary potential and evolutionary novelties. Our hypothesis is that wide-ranging taxa with similar ecological tolerances, yet of phylogenetically independent lineages, have been and currently are shaped by ecological and evolutionary forces that result in geographically concordant genetic patterns. We mapped previously published genetic diversity and unique variants of biparentally inherited markers and chloroplast sequences for 9 species from 188 and 275 populations, respectively, of the 4 woody dominant families of the austral temperate forest, an area considered a biodiversity hotspot. Spatial distribution patterns of genetic polymorphisms differed among taxa according to their ecological tolerances. Eight genetic hotspots were detected and we recommend conservation actions for some in the southern Coastal Range in Chile. Existing spatially explicit genetic data from multiple populations and species can help to identify biodiversity hotspots and guide conservation actions to establish science-based protected areas that will preserve the evolutionary potential of key habitats and species. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Inherited cardiomyopathies and sports participation.

PubMed

Zorzi, A; Pelliccia, A; Corrado, D

2018-03-01

Competitive sports activity is associated with an increased risk of sudden cardiovascular death in adolescents and young adults with inherited cardiomyopathies. Many young subjects aspire to continue competitive sport after a diagnosis of cardiomyopathy and the clinician is frequently confronted with the problem of eligibility and the request of designing specific exercise programs. Since inherited cardiomyopathies are the leading cause of sudden cardiovascular death during sports performance, a conservative approach implying disqualification of affected athletes from most competitive athletic disciplines is recommended by all the available international guidelines. On the other hand, we know that the health benefits of practicing recreational sports activity can overcome the potential arrhythmic risk in these patients, provided that the type and level of exercise are tailored on the basis of the specific risk profile of the underlying cardiomyopathy. This article will review the available evidence on the sports-related risk of sudden cardiac death and the recommendations regarding eligibility of individuals affected by inherited cardiomyopathies for sports activities.

Malformations among 289,365 Births Attributed to Mutations with Autosomal Dominant and Recessive and X-Linked Inheritance.

PubMed

Toufaily, M Hassan; Westgate, Marie-Noel; Nasri, Hanah; Holmes, Lewis B

2018-01-01

The number of malformations attributed to mutations with autosomal or X-linked patterns of inheritance has increased steadily since the cataloging began in the 1960s. These diagnoses have been based primarily on the pattern of phenotypic features among close relatives. A malformations surveillance program conducted in consecutive pregnancies can identify both known and "new" hereditary disorders. The Active Malformations Surveillance Program was carried out among 289,365 births over 41 years (1972-2012) at Brigham and Women's Hospital in Boston. The findings recorded by examining pediatricians and all consultants were reviewed by study clinicians to establish the most likely diagnoses. The findings in laboratory testing in the newborn period were reviewed, as well. One hundred ninety-six (0.06%) infants among 289,365 births had a malformation or malformation syndrome that was attributed to Mendelian inheritance. A total of 133 (68%) of the hereditary malformations were attributed to autosomal dominant inheritance, with 94 (71%) attributed to apparent spontaneous mutations. Forty-six (23%) were attributed to mutations with autosomal recessive inheritance, 17 associated with consanguinity. Seventeen (9%) were attributed to X-linked inheritance. Fifteen novel familial phenotypes were identified. The family histories showed that most (53 to 71%) of the affected infants were born, as a surprise, to healthy, unaffected parents. It is important for clinicians to discuss with surprised healthy parents how they can have an infant with an hereditary condition. Future studies, using DNA samples from consecutive populations of infants with malformations and whole genome sequencing, will identify many more mutations in loci associated with mendelizing phenotypes. Birth Defects Research 110:92-97, 2018.© 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Environmental stress and epigenetic transgenerational inheritance.

PubMed

Skinner, Michael K

2014-09-05

Previous studies have shown a wide variety of environmental toxicants and abnormal nutrition can promote the epigenetic transgenerational inheritance of disease. More recently a number of studies have indicated environmental stress can also promote epigenetic alterations that are transmitted to subsequent generations to induce pathologies. A recent study by Yao and colleagues demonstrated gestational exposure to restraint stress and forced swimming promoted preterm birth risk and adverse newborn outcomes generationally. This ancestral stress promoted the epigenetic transgenerational inheritance of abnormalities in the great-grand offspring of the exposed gestating female. Several studies now support the role of environmental stress in promoting the epigenetic transgenerational inheritance of disease. Observations suggest ancestral environmental stress may be a component of disease etiology in the current population.

Long Oskar Controls Mitochondrial Inheritance in Drosophila melanogaster.

PubMed

Hurd, Thomas Ryan; Herrmann, Beate; Sauerwald, Julia; Sanny, Justina; Grosch, Markus; Lehmann, Ruth

2016-12-05

Inherited mtDNA mutations cause severe human disease. In most species, mitochondria are inherited maternally through mechanisms that are poorly understood. Genes that specifically control the inheritance of mitochondria in the germline are unknown. Here, we show that the long isoform of the protein Oskar regulates the maternal inheritance of mitochondria in Drosophila melanogaster. We show that, during oogenesis, mitochondria accumulate at the oocyte posterior, concurrent with the bulk streaming and churning of the oocyte cytoplasm. Long Oskar traps and maintains mitochondria at the posterior at the site of primordial germ cell (PGC) formation through an actin-dependent mechanism. Mutating long oskar strongly reduces the number of mtDNA molecules inherited by PGCs. Therefore, Long Oskar ensures germline transmission of mitochondria to the next generation. These results provide molecular insight into how mitochondria are passed from mother to offspring, as well as how they are positioned and asymmetrically partitioned within polarized cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Extended inheritance from an organizational point of view.

PubMed

Pontarotti, Gaëlle

2015-12-01

In this paper, I argue that the increasing data about non-genetic inheritance requires the construction of a new conceptual framework that should complement the inclusive approaches already discussed in the literature. More precisely, I hold that this framework should be epistemologically relevant for evolutionary biologists in capturing the limits of extended inheritance and in reassessing the boundaries of biological systems that transmit traits to their offspring. I outline the first elements of an organizational account of extended inheritance. In this account, the category of inherited factors is neither restricted to genes nor extended to stable resources related to trans-generational similarities. Instead, it includes persisting constitutive elements appearing as difference makers for heterogeneous organizational constraints, namely for heterogeneous constitutive parts whose specific role is to harness flows of matter and energy across generations of clearly delimited extended organized systems. This both inclusive and restrictive framework opens an additional way to apprehend how extended inheritance may affect evolutionary trajectories.

Why does biparental plastid inheritance revive in angiosperms?

PubMed

Zhang, Quan; Sodmergen

2010-03-01

It is widely believed that plastid and mitochondrial genomes are inherited through the maternal parent. In plants, however, paternal transmission of these genomes is frequently observed, especially for the plastid genome. A male gametic trait, called potential biparental plastid inheritance (PBPI), occurs in up to 20% of angiosperm genera, implying a strong tendency for plastid transmission from the male lineage. Why do plants receive organelles from the male parents? Are there clues in plastids that will help to elucidate the evolution of plants? Reconstruction of the ancestral state of plastid inheritance patterns in a phylogenetic context provides insights into these questions. In particular, a recent report demonstrated the unilateral occurrence of PBPI in angiosperms. This result implies that nuclear cytoplasmic conflicts, a basic driving force for altering the mode of organelle inheritance, might have arisen specifically in angiosperms. Based on existing evidence, it is likely that biparental inheritance may have occurred to rescue angiosperm species with defective plastids.

Widow inheritance and HIV/AIDS in rural Uganda.

PubMed

Mabumba, E D; Mugyenyi, P; Batwala, V; Mulogo, E M; Mirembe, J; Khan, F A; Liljestrand, J

2007-10-01

Despite current efforts to combat HIV/AIDS through behavioural change, ingrained socio-cultural practices such as widow inheritance in south-western Uganda has not changed. Low education, unemployment, dowry, widows' socioeconomic demands and the inheritor's greed for the deceased's wealth, influence widow inheritance. Voluntary counselling and testing is needed for the widows and their inheritors; formal dowry should be removed from marriage and widow inheritance stripped of its sexual component.

Mutational analysis of the RB1 gene and the inheritance patterns of retinoblastoma in Jordan.

PubMed

Yousef, Yacoub A; Tbakhi, Abdelghani; Al-Hussaini, Maysa; AlNawaiseh, Ibrahim; Saab, Ala; Afifi, Amal; Naji, Maysa; Mohammad, Mona; Deebajah, Rasha; Jaradat, Imad; Sultan, Iyad; Mehyar, Mustafa

2018-04-01

Retinoblastoma (RB) is a childhood cancer developing in the retina due to RB1 pathologic variant. Herein we are evaluating the oncogenic mutations in the RB1 gene and the inheritance patterns of RB in the Jordanian patients. In this prospective study, the peripheral blood of 50 retinoblastoma patients was collected, genomic DNA was extracted, mutations were identified using Quantitative multiplex PCR (QM-PCR), Allele-specific PCR, Next Generation Sequencing analysis, and Sanger sequencing. In this cohort of 50 patients, 20(40%) patients had unilateral RB and 30(60%) were males. Overall, 36(72%) patients had germline disease, 17(47%) of whom had the same RB1 pathologic variant detected in one of the parents (inherited disease). In the bilateral group, all (100%) patients had germline disease; 13(43%) of them had inherited mutation. In the unilateral group, 6(30%) had germline disease, 4(20%) of them had inherited mutation. Nonsense mutation generating a stop codon and producing a truncated non-functional protein was the most frequent detected type of mutations (n = 15/36, 42%). Only one (2%) of the patients had mosaic mutation, and of the 17 inherited cases, 16(94%) had an unaffected carrier parent. In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilateral and bilateral cases including those with no family history.

Law & psychiatry: Murder, inheritance, and mental illness.

PubMed

Gold, Azgad; Appelbaum, Paul S

2011-07-01

Should a murderer be allowed to inherit the victim's estate? The question dates from biblical times, but most jurisdictions today have statutes in place that bar inheritance by convicted murderers. However, a special problem arises when the killer has a severe mental illness and has been found not guilty by reason of insanity. Should such people, who have not been convicted of a crime, be permitted to collect their inheritance? Jurisdictions vary in their responses, with the rules reflecting a mix of practical and moral considerations influenced by different perspectives about what determines the behavior of persons with mental illness.

Are duplicated genes responsible for anthracnose resistance in common bean?

PubMed

Costa, Larissa Carvalho; Nalin, Rafael Storto; Ramalho, Magno Antonio Patto; de Souza, Elaine Aparecida

2017-01-01

The race 65 of Colletotrichum lindemuthianum, etiologic agent of anthracnose in common bean, is distributed worldwide, having great importance in breeding programs for anthracnose resistance. Several resistance alleles have been identified promoting resistance to this race. However, the variability that has been detected within race has made it difficult to obtain cultivars with durable resistance, because cultivars may have different reactions to each strain of race 65. Thus, this work aimed at studying the resistance inheritance of common bean lines to different strains of C. lindemuthianum, race 65. We used six C. lindemuthianum strains previously characterized as belonging to the race 65 through the international set of differential cultivars of anthracnose and nine commercial cultivars, adapted to the Brazilian growing conditions and with potential ability to discriminate the variability within this race. To obtain information on the resistance inheritance related to nine commercial cultivars to six strains of race 65, these cultivars were crossed two by two in all possible combinations, resulting in 36 hybrids. Segregation in the F2 generations revealed that the resistance to each strain is conditioned by two independent genes with the same function, suggesting that they are duplicated genes, where the dominant allele promotes resistance. These results indicate that the specificity between host resistance genes and pathogen avirulence genes is not limited to races, it also occurs within strains of the same race. Further research may be carried out in order to establish if the alleles identified in these cultivars are different from those described in the literature.

Are duplicated genes responsible for anthracnose resistance in common bean?

PubMed Central

2017-01-01

The race 65 of Colletotrichum lindemuthianum, etiologic agent of anthracnose in common bean, is distributed worldwide, having great importance in breeding programs for anthracnose resistance. Several resistance alleles have been identified promoting resistance to this race. However, the variability that has been detected within race has made it difficult to obtain cultivars with durable resistance, because cultivars may have different reactions to each strain of race 65. Thus, this work aimed at studying the resistance inheritance of common bean lines to different strains of C. lindemuthianum, race 65. We used six C. lindemuthianum strains previously characterized as belonging to the race 65 through the international set of differential cultivars of anthracnose and nine commercial cultivars, adapted to the Brazilian growing conditions and with potential ability to discriminate the variability within this race. To obtain information on the resistance inheritance related to nine commercial cultivars to six strains of race 65, these cultivars were crossed two by two in all possible combinations, resulting in 36 hybrids. Segregation in the F2 generations revealed that the resistance to each strain is conditioned by two independent genes with the same function, suggesting that they are duplicated genes, where the dominant allele promotes resistance. These results indicate that the specificity between host resistance genes and pathogen avirulence genes is not limited to races, it also occurs within strains of the same race. Further research may be carried out in order to establish if the alleles identified in these cultivars are different from those described in the literature. PMID:28296933

Determination of epigenetic inheritance, genetic inheritance, and estimation of genome DNA methylation in a full-sib family of Cupressus sempervirens L.

PubMed

Avramidou, Evangelia V; Doulis, Andreas G; Aravanopoulos, Filippos A

2015-05-15

Genetic inheritance and epigenetic inheritance are significant determinants of plant evolution, adaptation and plasticity. We studied inheritance of restriction site polymorphisms by the f-AFLP method and epigenetic DNA cytosine methylation inheritance by the f-MSAP technique. The study involved parents and 190 progeny of a Cupressus sempervirens L. full-sib family. Results from AFLP genetic data revealed that 71.8% of the fragments studied are under Mendelian genetic control, whereas faithful Mendelian inheritance for the MSAP fragments was low (4.29%). Further, MSAP fragment analysis showed that total methylation presented a mean of 28.2%, which was higher than the midparent value, while maternal inheritance was higher (5.65%) than paternal (3.01%). Interestingly de novo methylation in the progeny was high (19.65%) compared to parental methylation. Genetic and epigenetic distances for parents and offspring were not correlated (R(2)=0.0005). Furthermore, we studied correlation of total relative methylation and CG methylation with growth (height, diameter). We found CG/CNG methylation (N: A, C, T) to be positively correlated with height and diameter, while total relative methylation and CG methylation were positively correlated with height. Results are discussed in light of further research needed and of their potential application in breeding. Copyright © 2015 Elsevier B.V. All rights reserved.

[Analysis on composition and medication regularities of prescriptions treating hypochondriac pain based on traditional Chinese medicine inheritance support system inheritance support platform].

PubMed

Zhao, Yan-qing; Teng, Jing

2015-03-01

To analyze the composition and medication regularities of prescriptions treating hypochondriac pain in Chinese journal full-text database (CNKI) based on the traditional Chinese medicine inheritance support system, in order to provide a reference for further research and development for new traditional Chinese medicines treating hypochondriac pain. The traditional Chinese medicine inheritance support platform software V2. 0 was used to build a prescription database of Chinese medicines treating hypochondriac pain. The software integration data mining method was used to distribute prescriptions according to "four odors", "five flavors" and "meridians" in the database and achieve frequency statistics, syndrome distribution, prescription regularity and new prescription analysis. An analysis were made for 192 prescriptions treating hypochondriac pain to determine the frequencies of medicines in prescriptions, commonly used medicine pairs and combinations and summarize 15 new prescriptions. This study indicated that the prescriptions treating hypochondriac pain in Chinese journal full-text database are mostly those for soothing liver-qi stagnation, promoting qi and activating blood, clearing heat and promoting dampness, and invigorating spleen and removing phlem, with a cold property and bitter taste, and reflect the principles of "distinguish deficiency and excess and relieving pain by smoothening meridians" in treating hypochondriac pain.

[Epigenetic inheritance and its possible role in the evolution of plant species].

PubMed

Lavrov, S A; Mavrodiev, E V

2003-01-01

As it is clear now, the level of gene expression in eukariotes is determined mainly by chromatin composition. Chromatin structure of a particular gene (it is a complex item, which includes nucleosome positioning, histone modifications and non-histone chromatin proteins) can be modified externally and is able to be inherited mitotically and meiotically. Changes in chromatine structure are the basis of so called epigenetic inheritance that occurs without modification of DNA sequence. One of the most striking examples of epigenetic inheritance in plants is epimutations--stable for many generation's alleles of some genes that do not differ in primary DNA structure. Molecular basis of epimutations seems to be DNA metylation. Epimutations may be widely distributed in nature and affect some basis morphological features that have a systematic significance. Possibility of inheritance of acquired epigenetic modifications lead us to reconsider an idea of multipLe independent origins of some plant forms (or ecotypes) under action of similar external conditions. Different populations of the same species may in this case be unrelated and has no common ancestor. Species should be considered as invariant of multiple ways of origin. Wide distribution of polyploids amongst higher plants suggests effective mechanism of repression of multicopy genes. Each allopolyploidisation event is followed by repression of random set of parent genes via changes in its chromatin structure. As a result, in the limits of the same hybrid formula may arise different stable combinations of epigenetically controlled features of parent species. These combinations may be classified as different species of other taxa.

Identifying Common Genetic Risk Factors of Diabetic Neuropathies

PubMed Central

Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

2015-01-01

Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

Inheritance patterns of morphological laterality in mouth opening of zebrafish, Danio rerio.

PubMed

Hata, Hiroki; Hori, Michio

2012-01-01

The inheritance patterns of asymmetry in mouth opening in zebrafish were investigated using crossing experiments. Zebrafish exhibit asymmetric laterality in mouth opening, with each individual having either a leftward (righty) or rightward (lefty) bias. All righty incrosses produced only righty F(1), whereas all lefty incrosses resulted in an F(1) L:R ratio of 2:1. All test crosses between lefty and righty individuals resulted in an F(1) L:R=1:1. These results were consistent with the hereditary pattern for Japanese medaka, three Tanganyikan cichlids, and a Japanese riverine goby. The pattern suggests a one-locus two-allele Mendelian model of inheritance, with the lefty allele being dominant over righty and the dominant homozygote being lethal. To determine the reason for the absence of lefty homozygotes, the survival rates of the offspring were examined according to developmental stage. Survival did not differ among combinations of parent laterality. Thus the mechanism underlying the lethality of the dominant homozygote remains unclear. This study showed that the mouth-opening laterality of zebrafish is genetically determined and that the direction follows a Mendelian inheritance pattern that is shared among cypriniform zebrafish, beloniform medaka, perciform cichlids, and a goby, suggesting a common genetic background in mouth-opening laterality among these species.

De novo and inherited private variants in MAP1B in periventricular nodular heterotopia.

PubMed

Heinzen, Erin L; O'Neill, Adam C; Zhu, Xiaolin; Allen, Andrew S; Bahlo, Melanie; Chelly, Jamel; Chen, Ming Hui; Dobyns, William B; Freytag, Saskia; Guerrini, Renzo; Leventer, Richard J; Poduri, Annapurna; Robertson, Stephen P; Walsh, Christopher A; Zhang, Mengqi

2018-05-01

Periventricular nodular heterotopia (PVNH) is a malformation of cortical development commonly associated with epilepsy. We exome sequenced 202 individuals with sporadic PVNH to identify novel genetic risk loci. We first performed a trio-based analysis and identified 219 de novo variants. Although no novel genes were implicated in this initial analysis, PVNH cases were found overall to have a significant excess of nonsynonymous de novo variants in intolerant genes (p = 3.27x10-7), suggesting a role for rare new alleles in genes yet to be associated with the condition. Using a gene-level collapsing analysis comparing cases and controls, we identified a genome-wide significant signal driven by four ultra-rare loss-of-function heterozygous variants in MAP1B, including one de novo variant. In at least one instance, the MAP1B variant was inherited from a parent with previously undiagnosed PVNH. The PVNH was frontally predominant and associated with perisylvian polymicrogyria. These results implicate MAP1B in PVNH. More broadly, our findings suggest that detrimental mutations likely arising in immediately preceding generations with incomplete penetrance may also be responsible for some apparently sporadic diseases.

[Inherited primitive and secondary polycythemia].

PubMed

Barba, T; Boileau, J-C; Pasquet, F; Hot, A; Pavic, M

2016-07-01

Myeloproliferative disorders and secondary polycythemia cover most of the polycythemia cases encountered in daily practice. Inherited polycythemias are rare entities that have to be suspected when the classical causes of acquired polycythemia have been ruled out. Recent advances were made in the understanding of these pathologies, which are still little known to the physicians. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of inherited polycythemia. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

The scurs inheritance: new insights from the French Charolais breed.

PubMed

Capitan, Aurélien; Grohs, Cécile; Gautier, Mathieu; Eggen, André

2009-07-06

Polled animals are valued in cattle industry because the absence of horns has a significant economic impact. However, some cattle are neither polled nor horned but have so-called scurs on their heads, which are corneous growths loosely attached to the skull. A better understanding of the genetic determinism of the scurs phenotype would help to fine map the polled locus. To date, only one study has attempted to map the scurs locus in cattle. Here, we have investigated the inheritance of the scurs phenotype in the French Charolais breed and examined whether the previously proposed localisation of the scurs locus on bovine chromosome 19 could be confirmed or not. Our results indicate that the inheritance pattern of the scurs phenotype in the French Charolais breed is autosomal recessive with complete penetrance in both sexes, which is different from what is reported for other breeds. The frequency of the scurs allele (Sc) reaches 69.9% in the French Charolais population. Eleven microsatellite markers on bovine chromosome 19 were genotyped in 267 offspring (33 half-sib and full-sib families). Both non-parametric and parametric linkage analyses suggest that in the French Charolais population the scurs locus may not map to the previously identified region. A new analysis of an Angus-Hereford and Hereford-Hereford pedigree published in 1978 enabled us to calculate the frequency of the Sc allele in the Hereford breed (89.4%) and to study the penetrance of this allele in males heterozygous for both polled and scurs loci (40%). This led us to revise the inheritance pattern of the scurs phenotype proposed for the Hereford breed and to suggest that allele Sc is not fully but partially dominant in double heterozygous males while it is always recessive in females. Crossbreeding involving the Charolais breed and other breeds gave results similar to those reported in the Hereford breed. Our results suggest the existence of unknown genetics factors modifying the expression of the

The scurs inheritance: new insights from the French Charolais breed

PubMed Central

Capitan, Aurélien; Grohs, Cécile; Gautier, Mathieu; Eggen, André

2009-01-01

Background Polled animals are valued in cattle industry because the absence of horns has a significant economic impact. However, some cattle are neither polled nor horned but have so-called scurs on their heads, which are corneous growths loosely attached to the skull. A better understanding of the genetic determinism of the scurs phenotype would help to fine map the polled locus. To date, only one study has attempted to map the scurs locus in cattle. Here, we have investigated the inheritance of the scurs phenotype in the French Charolais breed and examined whether the previously proposed localisation of the scurs locus on bovine chromosome 19 could be confirmed or not. Results Our results indicate that the inheritance pattern of the scurs phenotype in the French Charolais breed is autosomal recessive with complete penetrance in both sexes, which is different from what is reported for other breeds. The frequency of the scurs allele (Sc) reaches 69.9% in the French Charolais population. Eleven microsatellite markers on bovine chromosome 19 were genotyped in 267 offspring (33 half-sib and full-sib families). Both non-parametric and parametric linkage analyses suggest that in the French Charolais population the scurs locus may not map to the previously identified region. A new analysis of an Angus-Hereford and Hereford-Hereford pedigree published in 1978 enabled us to calculate the frequency of the Sc allele in the Hereford breed (89.4%) and to study the penetrance of this allele in males heterozygous for both polled and scurs loci (40%). This led us to revise the inheritance pattern of the scurs phenotype proposed for the Hereford breed and to suggest that allele Sc is not fully but partially dominant in double heterozygous males while it is always recessive in females. Crossbreeding involving the Charolais breed and other breeds gave results similar to those reported in the Hereford breed. Conclusion Our results suggest the existence of unknown genetics factors

Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.

PubMed

Hernandez, Dena G; Reed, Xylena; Singleton, Andrew B

2016-10-01

Parkinson's disease is a common, progressive neurodegenerative disorder, affecting 3% of those older than 75 years of age. Clinically, Parkinson's disease (PD) is associated with resting tremor, postural instability, rigidity, bradykinesia, and a good response to levodopa therapy. Over the last 15 years, numerous studies have confirmed that genetic factors contribute to the complex pathogenesis of PD. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for PD in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for PD. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease; however, no treatment methodologies have developed. Furthermore, for identified common risk alleles, the functional basis underlying risk principally remains unknown. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants in tandem with additional high-content, integrated datasets. This review discusses monogenic risk factors and mechanisms of Mendelian inheritance of Parkinson disease. Highly penetrant mutations in SNCA, Parkin, DJ-1, PINK 1, LRRK2 and VPS35 produce rare, monogenic forms of the disease, while unique variants within LRRK2 and GBA show incomplete penetrance and are strong risk factors for PD. Additionally, over 20 common variants with small effect sizes modulate disease risk. The challenge over the next decade is to strengthen genetic findings by assessing direct, biological consequences of risk variants in tandem with high-content, integrated datasets. This article is part of a special

Selective sweeps of mitochondrial DNA can drive the evolution of uniparental inheritance.

PubMed

Christie, Joshua R; Beekman, Madeleine

2017-08-01

Although the uniparental (or maternal) inheritance of mitochondrial DNA (mtDNA) is widespread, the reasons for its evolution remain unclear. Two main hypotheses have been proposed: selection against individuals containing different mtDNAs (heteroplasmy) and selection against "selfish" mtDNA mutations. Recently, uniparental inheritance was shown to promote adaptive evolution in mtDNA, potentially providing a third hypothesis for its evolution. Here, we explore this hypothesis theoretically and ask if the accumulation of beneficial mutations provides a sufficient fitness advantage for uniparental inheritance to invade a population in which mtDNA is inherited biparentally. In a deterministic model, uniparental inheritance increases in frequency but cannot replace biparental inheritance if only a single beneficial mtDNA mutation sweeps through the population. When we allow successive selective sweeps of mtDNA, however, uniparental inheritance can replace biparental inheritance. Using a stochastic model, we show that a combination of selection and drift facilitates the fixation of uniparental inheritance (compared to a neutral trait) when there is only a single selective mtDNA sweep. When we consider multiple mtDNA sweeps in a stochastic model, uniparental inheritance becomes even more likely to replace biparental inheritance. Our findings thus suggest that selective sweeps of beneficial mtDNA haplotypes can drive the evolution of uniparental inheritance. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Molecular mechanisms for protein-encoded inheritance

PubMed Central

Wiltzius, Jed J. W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

2013-01-01

Strains are phenotypic variants, encoded by nucleic acid sequences in chromosomal inheritance and by protein “conformations” in prion inheritance and transmission. But how is a protein “conformation” stable enough to endure transmission between cells or organisms? Here new polymorphic crystal structures of segments of prion and other amyloid proteins offer structural mechanisms for prion strains. In packing polymorphism, prion strains are encoded by alternative packings (polymorphs) of β-sheets formed by the same segment of a protein; in a second mechanism, segmental polymorphism, prion strains are encoded by distinct β-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring “conformations,” capable of encoding strains. These molecular mechanisms for transfer of information into prion strains share features with the familiar mechanism for transfer of information by nucleic acid inheritance, including sequence specificity and recognition by non-covalent bonds. PMID:19684598

DNA mutation motifs in the genes associated with inherited diseases.

PubMed

Růžička, Michal; Kulhánek, Petr; Radová, Lenka; Čechová, Andrea; Špačková, Naďa; Fajkusová, Lenka; Réblová, Kamila

2017-01-01

Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs) rarely associated with mutations (coldspots) and frequently associated with mutations (hotspots) exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutSα protein is noticeably bent.

Variation and inheritance of iron reductase activity in the roots of common bean (Phaseolus vulgaris L.) and association with seed iron accumulation QTL.

PubMed

Blair, Matthew W; Knewtson, Sharon Jb; Astudillo, Carolina; Li, Chee-Ming; Fernandez, Andrea C; Grusak, Michael A

2010-10-05

Iron deficiency anemia is a global problem which often affects women and children of developing countries. Strategy I plants, such as common bean (Phaseolus vulgaris L.) take up iron through a process that involves an iron reduction mechanism in their roots; this reduction is required to convert ferric iron to ferrous iron. Root absorbed iron is critical for the iron nutrition of the plant, and for the delivery of iron to the shoot and ultimately the seeds. The objectives of this study were to determine the variability and inheritance for iron reductase activity in a range of genotypes and in a low × high seed iron cross (DOR364 x G19833), to identify quantitative trait loci (QTL) for this trait, and to assess possible associations with seed iron levels. The experiments were carried out with hydroponically grown plants provided different amounts of iron varying between 0 and 20 μM Fe(III)-EDDHA. The parents, DOR364 and G19833, plus 13 other cultivated or wild beans, were found to differ in iron reductase activity. Based on these initial experiments, two growth conditions (iron limited and iron sufficient) were selected as treatments for evaluating the DOR364 × G19833 recombinant inbred lines. A single major QTL was found for iron reductase activity under iron-limited conditions (1 μM Fe) on linkage group b02 and another major QTL was found under iron sufficient conditions (15 μM Fe) on linkage group b11. Associations between the b11 QTL were found with several QTL for seed iron. Genes conditioning iron reductase activity in iron sufficient bean plants appear to be associated with genes contributing to seed iron accumulation. Markers for bean iron reductase (FRO) homologues were found with in silico mapping based on common bean synteny with soybean and Medicago truncatula on b06 and b07; however, neither locus aligned with the QTL for iron reductase activity. In summary, the QTL for iron reductase activity under iron limited conditions may be useful in

Paternal transmission of mitochondrial DNA as an integral part of mitochondrial inheritance in metapopulations of Drosophila simulans.

PubMed

Wolff, J N; Nafisinia, M; Sutovsky, P; Ballard, J W O

2013-01-01

Maternal inheritance is one of the hallmarks of animal mitochondrial DNA (mtDNA) and central to its success as a molecular marker. This mode of inheritance and subsequent lack of heterologous recombination allows us to retrace evolutionary relationships unambiguously down the matriline and without the confounding effects of recombinant genetic information. Accumulating evidence of biparental inheritance of mtDNA (paternal leakage), however, challenges our current understanding of how this molecule is inherited. Here, using Drosophila simulans collected from an East African metapopulation exhibiting recurring mitochondrial heteroplasmy, we conducted single fly matings and screened F1 offspring for the presence of paternal mtDNA using allele-specific PCR assays (AS-PCR). In all, 27 out of 4092 offspring were identified as harboring paternal mtDNA, suggesting a frequency of 0.66% paternal leakage in this species. Our findings strongly suggest that recurring mtDNA heteroplasmy as observed in natural populations of Drosophila simulans is most likely caused by repeated paternal leakage. Our findings further suggest that this phenomenon to potentially be an integral part of mtDNA inheritance in these populations and consequently of significance for mtDNA as a molecular marker.

Epigenetic Inheritance and the Intergenerational Transfer of Experience

ERIC Educational Resources Information Center

Harper, Lawrence

2005-01-01

Currently, behavioral development is thought to result from the interplay among genetic inheritance, congenital characteristics, cultural contexts, and parental practices as they directly impact the individual. Evolutionary ecology points to another contributor, epigenetic inheritance, the transmission to offspring of parental phenotypic responses…

Bi-parental cytoplasmic DNA inheritance in Wisteria (fabaceae): evidence from a natural experiment

Treesearch

Jennifer L. Trusty; Kataren J. Johnson; Graeme B. Lockaby; Leslie R. Goertzen

2007-01-01

Cytoplasmic inheritance was investigated in interspecific hybrids of Wisteria sinensis and W. floribunda. Species-specific nuclear, mitochondrial and plastid DNA markers were identified from wild-collected plants of each species in its native range. These markers provide evidence for the bi-parental transmission of plastids in...

22 CFR 71.3 - American claimants to foreign estates and inheritances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... inheritances. 71.3 Section 71.3 Foreign Relations DEPARTMENT OF STATE PROTECTION AND WELFARE OF AMERICANS....3 American claimants to foreign estates and inheritances. Where treaty provisions, local laws, or... foreign estates and inheritances. ...

Inherited Thrombophilia and Pregnancy Complications: Should We Test?

PubMed

Arachchillage, Deepa R J; Makris, Mike

2018-06-04

Recurrent miscarriages and pregnancy-related complications cause significant stress to couples looking for successful pregnancy outcome as well as to health care professionals. There is conflicting evidence with respect to the presence and the strength of associations between inherited thrombophilia and these complications. A complete thrombophilia screen is expensive, and no proven effective treatment for women with recurrent miscarriage and inherited thrombophilia is currently available. Based on the concept of microvascular thrombosis of the placenta, women with recurrent miscarriage and placenta-related complications frequently get treated with antithrombotic therapy. In this narrative review, the authors explore the evolving understanding and evidence of inherited thrombophilia in recurrent miscarriages and other pregnancy complications, and whether antithrombotic treatment would modify pregnancy outcome in women with inherited thrombophilia. Finally, they provide some personal recommendations based on available evidence for clinical practice. In summary, inherited thrombophilia testing is not required outside a clinical trial for women with recurrent pregnancy losses or late pregnancy complications. The presence of thrombophilia markers does not generally indicate additional therapy during pregnancy, even if a heritable thrombophilic defect is found in women with recurrent miscarriages or late pregnancy complications. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations.

PubMed

Tsangaris, E; Klaassen, R; Fernandez, C V; Yanofsky, R; Shereck, E; Champagne, J; Silva, M; Lipton, J H; Brossard, J; Michon, B; Abish, S; Steele, M; Ali, K; Dower, N; Athale, U; Jardine, L; Hand, J P; Odame, I; Canning, P; Allen, C; Carcao, M; Beyene, J; Roifman, C M; Dror, Y

2011-09-01

Inherited bone marrow failure syndromes (IBMFSs) often have substantial phenotypic overlap, thus genotyping is often critical for establishing a diagnosis. To determine the genetic characteristics and mutation profiles of IBMFSs, a comprehensive population-based study that prospectively enrols all typical and atypical cases without bias is required. The Canadian Inherited Marrow Failure Study is such a study, and was used to extract clinical and genetic information for patients enrolled up to May 2010. Among the 259 primary patients with IBMFS enrolled in the study, the most prevalent categories were Diamond-Blackfan anaemia (44 patients), Fanconi anaemia (39) and Shwachman-Diamond syndrome (35). The estimated incidence of the primary IBMFSs was 64.5 per 10(6) births, with Fanconi anaemia having the highest incidence (11.4 cases per 10(6) births). A large number of patients (70) had haematological and non-haematological features that did not fulfil the diagnostic criteria of any specific IBMFS category. Disease-causing mutations were identified in 53.5% of the 142 patients tested, and in 16 different genes. Ten novel mutations in SBDS, RPL5, FANCA, FANCG, MPL and G6PT were identified. The most common mutations were nonsense (31 alleles) and splice site (28). Genetic heterogeneity of most IBMFSs was evident; however, the most commonly mutated gene was SBDS, followed by FANCA and RPS19. From this the largest published comprehensive cohort of IBMFSs, it can be concluded that recent advances have led to successful genotyping of about half of the patients. Establishing a genetic diagnosis is still challenging and there is a critical need to develop novel diagnostic tools.

Regulation, cell differentiation and protein-based inheritance.

PubMed

Malagnac, Fabienne; Silar, Philippe

2006-11-01

Recent research using fungi as models provide new insight into the ability of regulatory networks to generate cellular states that are sufficiently stable to be faithfully transmitted to daughter cells, thereby generating epigenetic inheritance. Such protein-based inheritance is driven by infectious factors endowed with properties usually displayed by prions. We emphasize the contribution of regulatory networks to the emerging properties displayed by cells.

Establishment and evolution of the Australian Inherited Retinal Disease Register and DNA Bank.

PubMed

De Roach, John N; McLaren, Terri L; Paterson, Rachel L; O'Brien, Emily C; Hoffmann, Ling; Mackey, David A; Hewitt, Alex W; Lamey, Tina M

2013-07-01

Inherited retinal disease represents a significant cause of blindness and visual morbidity worldwide. With the development of emerging molecular technologies, accessible and well-governed repositories of data characterising inherited retinal disease patients is becoming increasingly important. This manuscript introduces such a repository. Participants were recruited from the Retina Australia membership, through the Royal Australian and New Zealand College of Ophthalmologists, and by recruitment of suitable patients attending the Sir Charles Gairdner Hospital visual electrophysiology clinic. Four thousand one hundred ninety-three participants were recruited. All participants were members of families in which the proband was diagnosed with an inherited retinal disease (excluding age-related macular degeneration). Clinical and family information was collected by interview with the participant and by examination of medical records. In 2001, we began collecting DNA from Western Australian participants. In 2009 this activity was extended Australia-wide. Genetic analysis results were stored in the register as they were obtained. The main outcome measurement was the number of DNA samples (with associated phenotypic information) collected from Australian inherited retinal disease-affected families. DNA was obtained from 2873 participants. Retinitis pigmentosa, Stargardt disease and Usher syndrome participants comprised 61.0%, 9.9% and 6.4% of the register, respectively. This resource is a valuable tool for investigating the aetiology of inherited retinal diseases. As new molecular technologies are translated into clinical applications, this well-governed repository of clinical and genetic information will become increasingly relevant for tasks such as identifying candidates for gene-specific clinical trials. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

RNA interference-based therapeutics for inherited long QT syndrome.

PubMed

Li, Guoliang; Ma, Shuting; Sun, Chaofeng

2015-08-01

Inherited long QT syndrome (LQTS) is an electrical heart disorder that manifests with syncope, seizures, and increased risk of torsades de pointes and sudden cardiac death. Dominant-negative current suppression is a mechanism by which pathogenic proteins disrupt the function of ion channels in inherited LQTS. However, current approaches for the management of inherited LQTS are inadequate. RNA interference (RNAi) is a powerful technique that is able to suppress or silence the expression of mutant genes. RNAi may be harnessed to knock out mRNAs that code for toxic proteins, and has been increasingly recognized as a potential therapeutic intervention for a range of conditions. The present study reviews the literature for RNAi-based therapeutics in the treatment of inherited LQTS. Furthermore, this review discusses the combined use of RNAi with the emerging technology of induced pluripotent stem cells for the treatment of inherited LQTS. In addition, key challenges that must be overcome prior to RNAi-based therapies becoming clinically applicable are addressed. In summary, RNAi-based therapy is potentially a powerful therapeutic intervention, although a number of difficulties remain unresolved.

RNA interference-based therapeutics for inherited long QT syndrome

PubMed Central

LI, GUOLIANG; MA, SHUTING; SUN, CHAOFENG

2015-01-01

Inherited long QT syndrome (LQTS) is an electrical heart disorder that manifests with syncope, seizures, and increased risk of torsades de pointes and sudden cardiac death. Dominant-negative current suppression is a mechanism by which pathogenic proteins disrupt the function of ion channels in inherited LQTS. However, current approaches for the management of inherited LQTS are inadequate. RNA interference (RNAi) is a powerful technique that is able to suppress or silence the expression of mutant genes. RNAi may be harnessed to knock out mRNAs that code for toxic proteins, and has been increasingly recognized as a potential therapeutic intervention for a range of conditions. The present study reviews the literature for RNAi-based therapeutics in the treatment of inherited LQTS. Furthermore, this review discusses the combined use of RNAi with the emerging technology of induced pluripotent stem cells for the treatment of inherited LQTS. In addition, key challenges that must be overcome prior to RNAi-based therapies becoming clinically applicable are addressed. In summary, RNAi-based therapy is potentially a powerful therapeutic intervention, although a number of difficulties remain unresolved. PMID:26622327

Meiosis Leads to Pervasive Copy-Number Variation and Distorted Inheritance of Accessory Chromosomes of the Wheat Pathogen Zymoseptoria tritici.

PubMed

Fouché, Simone; Plissonneau, Clémence; McDonald, Bruce A; Croll, Daniel

2018-06-01

Meiosis is one of the most conserved molecular processes in eukaryotes. The fidelity of pairing and segregation of homologous chromosomes has a major impact on the proper transmission of genetic information. Aberrant chromosomal transmission can have major phenotypic consequences, yet the mechanisms are poorly understood. Fungi are excellent models to investigate processes of chromosomal transmission, because many species have highly polymorphic genomes that include accessory chromosomes. Inheritance of accessory chromosomes is often unstable and chromosomal losses have little impact on fitness. We analyzed chromosomal inheritance in 477 progeny coming from two crosses of the fungal wheat pathogen Zymoseptoria tritici. For this, we developed a high-throughput screening method based on restriction site-associated DNA sequencing that generated dense coverage of genetic markers along each chromosome. We identified rare instances of chromosomal duplications (disomy) in core chromosomes. Accessory chromosomes showed high overall frequencies of disomy. Chromosomal rearrangements were found exclusively on accessory chromosomes and were more frequent than disomy. Accessory chromosomes present in only one of the parents in an analyzed cross were inherited at significantly higher rates than the expected 1:1 segregation ratio. Both the chromosome and the parental background had significant impacts on the rates of disomy, losses, rearrangements, and distorted inheritance. We found that chromosomes with higher sequence similarity and lower repeat content were inherited more faithfully. The large number of rearranged progeny chromosomes identified in this species will enable detailed analyses of the mechanisms underlying chromosomal rearrangement.

Extrachromosomal Inheritance of Carbon Dioxide Sensitivity in the Mosquito CULEX QUINQUEFASCIATUS

PubMed Central

Shroyer, Donald A.; Rosen, Leon

1983-01-01

Mosquitoes from a laboratory colony of Culex quinquefasciatus from Matsu Island, China, develop irreversible paralytic symptoms after exposure to carbon dioxide at 1°. This CO2 sensitivity is caused by an inherited infectious agent, probably a virus. Crossing studies between CO2-sensitive and -resistant mosquitoes showed that the sensitivity trait is inherited extrachromosomally in a fashion strictly analogous to the hereditary transmission of sigma virus in Drosophila melanogaster. Sensitivity could be maintained through maternal transmission alone, despite nine generations of backcrossing of "stabilized" CO2-sensitive females to males from a resistant strain. CO2-sensitive males crossed to resistant females transmitted sensitivity to a portion of their F 1 progeny, and only the female F1 sensitives were capable of further hereditary transmission.—Matsu, or a very similar hereditary infectious agent, is common in natural populations of Cx. quinquefasciatus on Oahu, Hawaii. Fifty-nine percent of the families reared from field-collected egg rafts contained CO2-sensitive mosquitoes, and some families contained only sensitive mosquitoes. PMID:6413297

Inherited renal tubulopathies associated with metabolic alkalosis: effects on blood pressure.

PubMed

Ariceta, Gema; Rodríguez-Soriano, Juan

2006-11-01

Inherited tubular disorders associated with metabolic alkalosis are caused by several gene mutations encoding different tubular transporters responsible for NaCl renal handling. Body volume and renin-angiotensin-aldosterone system status are determined by NaCl reabsorption in the distal nephron. Two common hallmarks in affected individuals: hypokalemia and normal / high blood pressure, support the differential diagnosis. Bartter's syndrome, characterized by hypokalemia and normal blood pressure, is a heterogenic disease caused by the loss of function of SLC12A1 (type 1), KCNJ1 (type 2), CLCNKB (type 3), or BSND genes (type 4). As a result, patients present with renal salt wasting and hypercalciuria. Gitelman's syndrome is caused by the loss of funcion of the SLC12A3 gene and may resemble Bartter's syndrome, though is associated with the very low urinary calcium. Liddle's syndrome, also with similar phenotype but with hypertension, is produced by the gain of function of the SNCC1B or SNCC1G genes, and must be distinguished from other entities of inherited hypertension such as Apparently Mineralocorticoid Excess, of glucocorticoid remediable hypertension.

Co-inheritance of α-thalassaemia and β-thalassaemia in a prenatal screening population in mainland China.

PubMed

Li, Jian; Xie, Xing-Mei; Liao, Can; Li, Dong-Zhi

2014-12-01

To determine the prevalence of α-thalassaemia in β-thalassaemia individuals in a Chinese population. The standard diagnostic marker for β-thalassaemia was elevation of the Hb A2 level (>3.5%) with low mean corpuscular volume. The common α-thalassaemia mutations were studied by molecular analysis in all identified β-thalassaemia carriers. A prevalence rate of 3.3% for β-thalassaemia was found in our population; α- and β-thalassaemia interactions were found to co-exist in 17.8% of the β-thalassaemia carriers. The -SEA deletion was the most common α-thalassaemia mutation co-inherited with β-thalassaemia, followed by the -α3.7 deletion, the -α4.2 deletion, Hb Quong Sze, and Hb Constant Spring. Our results suggest that it could be valuable to study co-existing α-globin mutations in subjects with β-thalassaemia trait in a prenatal screening programme, especially in populations with a high prevalence of haemoglobinopathies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

PubMed

Procopio, V; Manti, S; Bianco, G; Conti, G; Romeo, A; Maimone, F; Arrigo, T; Cutrupi, M C; Salpietro, C; Cuppari, C

2018-01-30

Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing

PubMed Central

Walsh, Tom; Lee, Ming K.; Casadei, Silvia; Thornton, Anne M.; Stray, Sunday M.; Pennil, Christopher; Nord, Alex S.; Mandell, Jessica B.; Swisher, Elizabeth M.; King, Mary-Claire

2010-01-01

Inherited loss-of-function mutations in the tumor suppressor genes BRCA1, BRCA2, and multiple other genes predispose to high risks of breast and/or ovarian cancer. Cancer-associated inherited mutations in these genes are collectively quite common, but individually rare or even private. Genetic testing for BRCA1 and BRCA2 mutations has become an integral part of clinical practice, but testing is generally limited to these two genes and to women with severe family histories of breast or ovarian cancer. To determine whether massively parallel, “next-generation” sequencing would enable accurate, thorough, and cost-effective identification of inherited mutations for breast and ovarian cancer, we developed a genomic assay to capture, sequence, and detect all mutations in 21 genes, including BRCA1 and BRCA2, with inherited mutations that predispose to breast or ovarian cancer. Constitutional genomic DNA from subjects with known inherited mutations, ranging in size from 1 to >100,000 bp, was hybridized to custom oligonucleotides and then sequenced using a genome analyzer. Analysis was carried out blind to the mutation in each sample. Average coverage was >1200 reads per base pair. After filtering sequences for quality and number of reads, all single-nucleotide substitutions, small insertion and deletion mutations, and large genomic duplications and deletions were detected. There were zero false-positive calls of nonsense mutations, frameshift mutations, or genomic rearrangements for any gene in any of the test samples. This approach enables widespread genetic testing and personalized risk assessment for breast and ovarian cancer. PMID:20616022

Common breast cancer susceptibility loci are associated with triple negative breast cancer

PubMed Central

Stevens, Kristen N.; Vachon, Celine M.; Lee, Adam M.; Slager, Susan; Lesnick, Timothy; Olswold, Curtis; Fasching, Peter A.; Miron, Penelope; Eccles, Diana; Carpenter, Jane E.; Godwin, Andrew K.; Ambrosone, Christine; Winqvist, Robert; Schmidt, Marjanka K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor; Hartmann, Arndt; Beckmann, Matthias W.; Schulz-Wendtland, Rüdiger; Ekici, Arif B.; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Graham, Nikki; Hein, Rebecca; Nickels, Stephan; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Hans-Peter; Konstantopoulou, Irene; Fostira, Florentia; Pectasides, Dimitrios; Dimopoulos, Athanasios M.; Fountzilas, George; Clarke, Christine L.; Balleine, Rosemary; Olson, Janet E.; Fredericksen, Zachary; Diasio, Robert B.; Pathak, Harsh; Ross, Eric; Weaver, JoEllen; Rüdiger, Thomas; Försti, Asta; Dünnebier, Thomas; Ademuyiwa, Foluso; Kulkarni, Swati; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Ko, Yon-Dschun; Van Limbergen, Erik; Janssen, Hilde; Peto, Julian; Fletcher, Olivia; Giles, Graham G.; Baglietto, Laura; Verhoef, Senno; Tomlinson, Ian; Kosma, Veli-Matti; Beesley, Jonathan; Greco, Dario; Blomqvist, Carl; Irwanto, Astrid; Liu, Jianjun; Blows, Fiona M.; Dawson, Sarah-Jane; Margolin, Sara; Mannermaa, Arto; Martin, Nicholas G.; Montgomery, Grant W; Lambrechts, Diether; dos Santos Silva, Isabel; Severi, Gianluca; Hamann, Ute; Pharoah, Paul; Easton, Douglas F.; Chang-Claude, Jenny; Yannoukakos, Drakoulis; Nevanlinna, Heli; Wang, Xianshu; Couch, Fergus J.

2012-01-01

Triple negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiological factors which promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome wide association studies (GWAS) display heterogeneity of effect among breast cancer subtypes as defined by estrogen receptor (ER) and progesterone receptor (PR) status. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple negative breast cancer and 4,978 healthy controls. We identified six single nucleotide polymorphisms (SNPs) significantly associated with risk of triple negative breast cancer, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.11) and rs8100241 (19p13.11). Together, our results provide convincing evidence of genetic susceptibility for triple negative breast cancer. PMID:21844186

Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

PubMed

Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

2017-10-01

Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Occupational Inheritance in Service Academy Cadets and Midshipmen

ERIC Educational Resources Information Center

Roller, Brain; Doerries, Lee E.

2008-01-01

Occupational inheritance refers to the phenomenon where sons and daughters follow in the career paths of their parents. Historically this has been documented in the areas of engineering, medicine and education. This study investigated the phenomenon of occupational inheritance as it pertains to military service. Archival data provided by the…

Mutation databases for inherited renal disease: are they complete, accurate, clinically relevant, and freely available?

PubMed

Savige, Judy; Dagher, Hayat; Povey, Sue

2014-07-01

This study examined whether gene-specific DNA variant databases for inherited diseases of the kidney fulfilled the Human Variome Project recommendations of being complete, accurate, clinically relevant and freely available. A recent review identified 60 inherited renal diseases caused by mutations in 132 genes. The disease name, MIM number, gene name, together with "mutation" or "database," were used to identify web-based databases. Fifty-nine diseases (98%) due to mutations in 128 genes had a variant database. Altogether there were 349 databases (a median of 3 per gene, range 0-6), but no gene had two databases with the same number of variants, and 165 (50%) databases included fewer than 10 variants. About half the databases (180, 54%) had been updated in the previous year. Few (77, 23%) were curated by "experts" but these included nine of the 11 with the most variants. Even fewer databases (41, 12%) included clinical features apart from the name of the associated disease. Most (223, 67%) could be accessed without charge, including those for 50 genes (40%) with the maximum number of variants. Future efforts should focus on encouraging experts to collaborate on a single database for each gene affected in inherited renal disease, including both unpublished variants, and clinical phenotypes. © 2014 WILEY PERIODICALS, INC.

Atrazine induced epigenetic transgenerational inheritance of disease, lean phenotype and sperm epimutation pathology biomarkers

PubMed Central

McBirney, Margaux; King, Stephanie E.; Pappalardo, Michelle; Houser, Elizabeth; Unkefer, Margaret; Nilsson, Eric; Sadler-Riggleman, Ingrid; Beck, Daniel; Winchester, Paul

2017-01-01

Ancestral environmental exposures to a variety of environmental toxicants and other factors have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The current study examined the potential transgenerational actions of the herbicide atrazine. Atrazine is one of the most commonly used herbicides in the agricultural industry, in particular with corn and soy crops. Outbred gestating female rats were transiently exposed to a vehicle control or atrazine. The F1 generation offspring were bred to generate the F2 generation and then the F2 generation bred to generate the F3 generation. The F1, F2 and F3 generation control and atrazine lineage rats were aged and various pathologies investigated. The male sperm were collected to investigate DNA methylation differences between the control and atrazine lineage sperm. The F1 generation offspring (directly exposed as a fetus) did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease and mammary tumors in males and females, early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations (motor hyperactivity) and a lean phenotype in males and females. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The transgenerational transmission of disease requires germline (egg or sperm) epigenetic alterations. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified in the F1, F2 and F3 generations. Gene associations with the DMRs were identified. For the transgenerational F3 generation sperm, unique sets of DMRs (epimutations) were found to be associated with the lean phenotype or testis

Proteomics analysis for asymmetric inheritance of preexisting proteins between mother and daughter cells in budding yeast.

PubMed

Okada, Mitsuhiro; Kusunoki, Shunta; Ishibashi, Yuko; Kito, Keiji

2017-06-01

In budding yeast, a mother cell can produce a finite number of daughter cells over its life. The accumulation of a variety of types of damaged components has an impact on the aging process. Asymmetrical inheritance during cell division causes these aberrant intracellular constituents to be retained in mother cells and prevents them from segregating to daughter cells. However, the understanding of asymmetrical inheritance of individual proteins that are damaged or old age, and their relevance to the aging process, has been limited. The aim of this study is to propose a proteomics strategy for asymmetrical inheritance of preexisting proteins between mother and daughter cells. During synchronous culture for one generation, newly synthesized proteins were labeled with stable isotope amino acids to discriminate preexisting proteins originally expressed in mother cells, followed by separation of mother and daughter cells using a conventional method based on biotin labeling. Isotope incorporation ratios for individual proteins were quantified using mass spectrometry. We successfully identified 21 proteins whose preexisting versions were asymmetrically inherited in mother cells, including plasma membrane transporter involved in the aging process and organelle-anchoring proteins related to the stress response to misfolded proteins. Thus, our approach would be useful for making catalog of asymmetrically inherited proteins. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Whole exome sequencing for familial bicuspid aortic valve identifies putative variants.

PubMed

Martin, Lisa J; Pilipenko, Valentina; Kaufman, Kenneth M; Cripe, Linda; Kottyan, Leah C; Keddache, Mehdi; Dexheimer, Phillip; Weirauch, Matthew T; Benson, D Woodrow

2014-10-01

Bicuspid aortic valve (BAV) is the most common congenital cardiovascular malformation. Although highly heritable, few causal variants have been identified. The purpose of this study was to identify genetic variants underlying BAV by whole exome sequencing a multiplex BAV kindred. Whole exome sequencing was performed on 17 individuals from a single family (BAV=3; other cardiovascular malformation, 3). Postvariant calling error control metrics were established after examining the relationship between Mendelian inheritance error rate and coverage, quality score, and call rate. To determine the most effective approach to identifying susceptibility variants from among 54 674 variants passing error control metrics, we evaluated 3 variant selection strategies frequently used in whole exome sequencing studies plus extended family linkage. No putative rare, high-effect variants were identified in all affected but no unaffected individuals. Eight high-effect variants were identified by ≥2 of the commonly used selection strategies; however, these were either common in the general population (>10%) or present in the majority of the unaffected family members. However, using extended family linkage, 3 synonymous variants were identified; all 3 variants were identified by at least one other strategy. These results suggest that traditional whole exome sequencing approaches, which assume causal variants alter coding sense, may be insufficient for BAV and other complex traits. Identification of disease-associated variants is facilitated by the use of segregation within families. © 2014 American Heart Association, Inc.

Inheritance for software reuse: The good, the bad, and the ugly

NASA Technical Reports Server (NTRS)

Sitaraman, Murali; Eichmann, David A.

1992-01-01

Inheritance is a powerful mechanism supported by object-oriented programming languages to facilitate modifications and extensions of reusable software components. This paper presents a taxonomy of the various purposes for which an inheritance mechanism can be used. While some uses of inheritance significantly enhance software reuse, some others are not as useful and in fact, may even be detrimental to reuse. The paper discusses several examples, and argues for a programming language design that is selective in its support for inheritance.

CZ: Multimethods and Multiple Inheritance Without Diamonds

DTIC Science & Technology

2009-12-01

Language. Digital Press, second edition , 1990. 31 [48] C. Szyperski, S. Omohundro, and S. Murer. Engineering a programming language: The type and class...CZ:Multimethods andMultiple Inheritance Without Diamonds 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Expressiveness is retained through two features: a “requires” construct that provides a form of subtyping without inheritance (in- spired by Scala [39]), and a

Familial epilepsy in Algeria: Clinical features and inheritance profiles.

PubMed

Chentouf, Amina; Dahdouh, Aïcha; Guipponi, Michel; Oubaiche, Mohand Laïd; Chaouch, Malika; Hamamy, Hanan; Antonarakis, Stylianos E

2015-09-01

To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families. Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed. The epilepsy type was classified according to the criteria of the International League Against Epilepsy and modes of inheritance were deduced from pedigree analysis. The study population included 40 probands; 23 male (57.5%) and 17 female subjects (42.5%). The mean age of seizure onset was 9.5 ± 6.1 years. According to seizure onset, 16 patients (40%) had focal seizures and 20 (50%) had generalized seizures. Seizure control was achieved for two patients (5%) for 10 years, while 28 (70%) were seizure-free for 3 months. Eleven patients (27.5%) had prior febrile seizures, 12 were diagnosed with psychiatric disorders and four families had syndromic epilepsy. The consanguinity rate among parents of affected was 50% with phenotypic concordance observed in 25 families (62.5%). Pedigree analysis suggested autosomal dominant (AD) inheritance with or without reduced penetrance in 18 families (45%), probable autosomal recessive (AR) inheritance in 14 families (35%), and an X-linked recessive inheritance in one family. This study reveals large Algerian families with multigenerational inheritance of epilepsy. Molecular testing such as exome sequencing would clarify the genetic basis of epilepsy in some of our families. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.

PubMed

Vissing, John; Barresi, Rita; Witting, Nanna; Van Ghelue, Marijke; Gammelgaard, Lise; Bindoff, Laurence A; Straub, Volker; Lochmüller, Hanns; Hudson, Judith; Wahl, Christoph M; Arnardottir, Snjolaug; Dahlbom, Kathe; Jonsrud, Christoffer; Duno, Morten

2016-08-01

Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co-segregated with evidence of muscle disease and autosomal dominant transmission in several generations. Evidence of muscle disease was indicated by muscle pain, muscle weakness and wasting, significant fat replacement of muscles on imaging, myopathic changes on muscle biopsy and loss of calpain 3 protein on western blotting. Thirty-one of 34 patients had elevated creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation. This study provides strong evidence that heterozygosity for the c.643_663del21 deletion in CAPN3 results in a dominantly inherited muscle disease. The normal expression of mutated mRNA and the severe loss of calpain 3 on western blotting, suggest a dominant negative effect with a loss-of-function mechanism affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings

Using haplotypes to unravel the inheritance of Holstein coat color for a larger audience

USDA-ARS?s Scientific Manuscript database

Haplotype testing identifies single-nucleotide polymorphisms that bracket a group of alleles from several different genes located on a specific chromosomal section of DNA. For a trait with a limited number of genotypes and phenotypes, the rules of inheritance can be determined by matching up certain...

Prevalence and Mode of Inheritance of the Dal Blood Group in Dogs in North America.

PubMed

Goulet, S; Giger, U; Arsenault, J; Abrams-Ogg, A; Euler, C C; Blais, M-C

2017-05-01

The Dal blood group system was identified a decade ago by the accidental sensitization of a Dal- Dalmatian with a Dal+ blood transfusion. Similar Dal-related blood incompatibilities have been suspected in other Dalmatians, Doberman Pinschers, and other breeds. To determine the prevalence and mode of inheritance of the Dal antigen expression in dogs. A total of 1130 dogs including 128 Dalmatians, 432 Doberman Pinschers, 21 Shih Tzus, and 549 dogs of other breeds including 228 blood donors were recruited from North America between 2008 and 2015. Prospectively, dogs were blood typed for Dal applying a gel column technique using polyclonal canine anti-Dal sera. Pedigrees from 8 typed families were analyzed. The prevalence of the Dal+ blood type varied between 85.6 and 100% in Dalmatians and 43.3-78.6% in Doberman Pinschers depending on geographical area. Dal- dogs were identified mostly in Dalmatians (15/128; 11.7%), Doberman Pinschers (183/432; 42.4%), and Shih Tzus (12/21; 57.1%), and sporadically in mixed-breed dogs (3/122; 2.5%), Lhasa Apsos (1/6) and Bichon Frises (1/3). Only 6/245 (2.4%) blood donors were found to be Dal-, including 5 Doberman Pinschers. The mode of inheritance of the Dal+ phenotype was determined to be autosomal dominant. The high percentage of Dal- Doberman Pinchers, Dalmatians and Shih Tzus increases their risk of being sensitized by a blood transfusion from the common Dal+ donor. Extended Dal typing is recommended in those breeds and in dogs when blood incompatibility problems arise after initial transfusions. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Territory inheritance in clownfish.

PubMed

Buston, Peter M

2004-05-07

Animal societies composed of breeders and non-breeders present a challenge to evolutionary theory because it is not immediately apparent how natural selection can preserve the genes that underlie non-breeding strategies. The clownfish Amphiprion percula forms groups composed of a breeding pair and 0-4 non-breeders. Non-breeders gain neither present direct, nor present indirect benefits from the association. To determine whether non-breeders obtain future direct benefits, I investigated the pattern of territory inheritance. I show that non-breeders stand to inherit the territory within which they reside. Moreover, they form a perfect queue for breeding positions; a queue from which nobody disperses and within which nobody contests. I suggest that queuing might be favoured by selection because it confers a higher probability of attaining breeding status than either dispersing or contesting. This study illustrates that, within animal societies, individuals may tolerate non-breeding positions solely because of their potential to realize benefits in the future.

Territory inheritance in clownfish.

PubMed Central

Buston, Peter M

2004-01-01

Animal societies composed of breeders and non-breeders present a challenge to evolutionary theory because it is not immediately apparent how natural selection can preserve the genes that underlie non-breeding strategies. The clownfish Amphiprion percula forms groups composed of a breeding pair and 0-4 non-breeders. Non-breeders gain neither present direct, nor present indirect benefits from the association. To determine whether non-breeders obtain future direct benefits, I investigated the pattern of territory inheritance. I show that non-breeders stand to inherit the territory within which they reside. Moreover, they form a perfect queue for breeding positions; a queue from which nobody disperses and within which nobody contests. I suggest that queuing might be favoured by selection because it confers a higher probability of attaining breeding status than either dispersing or contesting. This study illustrates that, within animal societies, individuals may tolerate non-breeding positions solely because of their potential to realize benefits in the future. PMID:15252999

Familial central precocious puberty suggests autosomal dominant inheritance.

PubMed

de Vries, Liat; Kauschansky, Arieh; Shohat, Mordechai; Phillip, Moshe

2004-04-01

The prevalence of precocious puberty is higher in certain ethnic groups, and some cases may be familial. The aim of this study was to investigate the mode of inheritance of familial precocious puberty and to identify characteristics that distinguish familial from isolated precocious puberty. Of the 453 children referred to our center for suspected precocious puberty between January 1, 1997, and December 31, 2000, 156 (147 girls and 9 boys) were found to have idiopathic central precocious puberty, which was familial in 43 (42 girls and 1 boy) (27.5%). Data of the familial and sporadic cases were compared. The familial group was characterized by a significantly lower maternal age at menarche than the sporadic group (mean, 11.47 +/- 1.96 vs. 12.66 +/- 1.18 yr; P = 0.0001) and more advanced puberty at admission (Tanner stage 2, 56.5% vs. 78.1%; P = 0.006). Segregation analysis was used to study the mode of inheritance. The segregation ratio for precocious puberty was 0.38 (0.45 after exclusion of young siblings) assuming incomplete penetrance and 0.58 (0.65 after exclusion of young siblings) assuming complete ascertainment. These results suggest autosomal dominant transmission with incomplete, sex-dependent penetrance.

Familial urothelial cell carcinoma of the bladder with autosomal dominant inheritance and late onset phenotype.

PubMed

Brown, Robin; Donnelly, Deirdre E; Allen, Derek; Loughrey, Maurice B; Morrison, Patrick J

2014-01-01

Familial Urothelial cell bladder cancer is rare. We report two families with urothelial cell carcinoma (UCC) of bladder with family history in other relatives, displaying probable autosomal dominant inheritance and a late onset pure UCC phenotype, and document the phenotype in each family. Descriptive familial study on two pedigrees over three generations. Two families with UCC bladder were identified, and the phenotype documented, each family having three cases of late onset UCC. Some cases of UCC are hereditary and may display autosomal dominant inheritance with late onset of the cancer. Clinicians should be aware of the existence of a familial late onset UCC phenotype when managing cases of UCC.

Maternal telomere length inheritance in the king penguin.

PubMed

Reichert, S; Rojas, E R; Zahn, S; Robin, J-P; Criscuolo, F; Massemin, S

2015-01-01

Telomeres are emerging as a biomarker for ageing and survival, and are likely important in shaping life-history trade-offs. In particular, telomere length with which one starts in life has been linked to lifelong survival, suggesting that early telomere dynamics are somehow related to life-history trajectories. This result highlights the importance of determining the extent to which telomere length is inherited, as a crucial factor determining early life telomere length. Given the scarcity of species for which telomere length inheritance has been studied, it is pressing to assess the generality of telomere length inheritance patterns. Further, information on how this pattern changes over the course of growth in individuals living under natural conditions should provide some insight on the extent to which environmental constraints also shape telomere dynamics. To fill this gap partly, we followed telomere inheritance in a population of king penguins (Aptenodytes patagonicus). We tested for paternal and maternal influence on chick initial telomere length (10 days old after hatching), and how these relationships changed with chick age (at 70, 200 and 300 days old). Based on a correlative approach, offspring telomere length was positively associated with maternal telomere length early in life (at 10 days old). However, this relationship was not significant at older ages. These data suggest that telomere length in birds is maternally inherited. Nonetheless, the influence of environmental conditions during growth remained an important factor shaping telomere length, as the maternal link disappeared with chicks' age.

Gene panel testing for inherited cancer risk.

PubMed

Hall, Michael J; Forman, Andrea D; Pilarski, Robert; Wiesner, Georgia; Giri, Veda N

2014-09-01

Next-generation sequencing technologies have ushered in the capability to assess multiple genes in parallel for genetic alterations that may contribute to inherited risk for cancers in families. Thus, gene panel testing is now an option in the setting of genetic counseling and testing for cancer risk. This article describes the many gene panel testing options clinically available to assess inherited cancer susceptibility, the potential advantages and challenges associated with various types of panels, clinical scenarios in which gene panels may be particularly useful in cancer risk assessment, and testing and counseling considerations. Given the potential issues for patients and their families, gene panel testing for inherited cancer risk is recommended to be offered in conjunction or consultation with an experienced cancer genetic specialist, such as a certified genetic counselor or geneticist, as an integral part of the testing process. Copyright © 2014 by the National Comprehensive Cancer Network.

Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations

PubMed Central

Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K.

2012-01-01

Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PMID:23049995

Parallel Mapping and Simultaneous Sequencing Reveals Deletions in BCAN and FAM83H Associated with Discrete Inherited Disorders in a Domestic Dog Breed

PubMed Central

Forman, Oliver P.; Hayward, Louisa J.; Ricketts, Sally L.; Mellersh, Cathryn S.

2012-01-01

The domestic dog (Canis familiaris) segregates more naturally-occurring diseases and phenotypic variation than any other species and has become established as an unparalled model with which to study the genetics of inherited traits. We used a genome-wide association study (GWAS) and targeted resequencing of DNA from just five dogs to simultaneously map and identify mutations for two distinct inherited disorders that both affect a single breed, the Cavalier King Charles Spaniel. We investigated episodic falling (EF), a paroxysmal exertion-induced dyskinesia, alongside the phenotypically distinct condition congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID), commonly known as dry eye curly coat syndrome. EF is characterised by episodes of exercise-induced muscular hypertonicity and abnormal posturing, usually occurring after exercise or periods of excitement. CKCSID is a congenital disorder that manifests as a rough coat present at birth, with keratoconjunctivitis sicca apparent on eyelid opening at 10–14 days, followed by hyperkeratinisation of footpads and distortion of nails that develops over the next few months. We undertook a GWAS with 31 EF cases, 23 CKCSID cases, and a common set of 38 controls and identified statistically associated signals for EF and CKCSID on chromosome 7 (Praw 1.9×10−14; Pgenome = 1.0×10−5) and chromosome 13 (Praw 1.2×10−17; Pgenome = 1.0×10−5), respectively. We resequenced both the EF and CKCSID disease-associated regions in just five dogs and identified a 15,724 bp deletion spanning three exons of BCAN associated with EF and a single base-pair exonic deletion in FAM83H associated with CKCSID. Neither BCAN or FAM83H have been associated with equivalent disease phenotypes in any other species, thus demonstrating the ability to use the domestic dog to study the genetic basis of more than one disease simultaneously in a single breed and to identify multiple novel candidate genes in parallel

Finding Common Ground: Identifying and Eliciting Metacognition in ePortfolios across Contexts

ERIC Educational Resources Information Center

Bokser, Julie A.; Brown, Sarah; Chaden, Caryn; Moore, Michael; Cleary, Michelle Navarre; Reed, Susan; Seifert, Eileen; Zecker, Liliana Barro; Wozniak, Kathryn

2016-01-01

Research has suggested ePortfolios reveal and support students' metacognition, that is, their awareness, tracking, and evaluation of their learning over time. However, due to the wide variety of purposes and audiences for ePortfolios, it has been unclear whether there might be common criteria for identifying and assessing metacognition in…

Use/disuse paradigms are ubiquitous concepts in characterizing the process of inheritance.

PubMed

Veigl, Sophie Juliane

2017-12-02

In recent years, a Lamarckian theme has found its way back into academic discourse on evolution and inheritance. Especially the emerging field of transgenerational small RNAs has provided at least a proof of concept for the inheritance of acquired traits. Yet it remains unclear whether the Lamarckian concept of inheritance will in fact have its rennaisance or whether it will remain the rallying cry for the outlaws, heretics and enfants terribles of molecular biology. As unclear as the future of Lamarckian theory is its content and reference. Since the formulation of the Philosophie Zoologique, Lamarckian thought has been de- and reconfiguring in and out of the scientific literature and become an umbrella-term for all kinds of unconventional modes of inheritance. This essay will argue that heritable small RNAs might in fact provide a case of genuine Lamarckian inheritance. Moreover, it will be claimed that not only the very broad concept of "inheritance of acquired traits" applies, but also that Lamarck's mechanistic insight into a use/disuse relation might help to explain a specific mode of transgenerational inheritance.

Fractional populations in multiple gene inheritance.

PubMed

Chung, Myung-Hoon; Kim, Chul Koo; Nahm, Kyun

2003-01-22

With complete knowledge of the human genome sequence, one of the most interesting tasks remaining is to understand the functions of individual genes and how they communicate. Using the information about genes (locus, allele, mutation rate, fitness, etc.), we attempt to explain population demographic data. This population evolution study could complement and enhance biologists' understanding about genes. We present a general approach to study population genetics in complex situations. In the present approach, multiple allele inheritance, multiple loci inheritance, natural selection and mutations are allowed simultaneously in order to consider a more realistic situation. A simulation program is presented so that readers can readily carry out studies with their own parameters. It is shown that the multiplicity of the loci greatly affects the demographic results of fractional population ratios. Furthermore, the study indicates that some high infant mortality rates due to congenital anomalies can be attributed to multiple loci inheritance. The simulation program can be downloaded from http://won.hongik.ac.kr/~mhchung/index_files/yapop.htm. In order to run this program, one needs Visual Studio.NET platform, which can be downloaded from http://msdn.microsoft.com/netframework/downloads/default.asp.

Inheritance of dermatoglyphic asymmetry and diversity traits in twins based on factor: variance decomposition analysis.

PubMed

Karmakar, Bibha; Malkin, Ida; Kobyliansky, Eugene

2013-06-01

Dermatoglyphic asymmetry and diversity traits from a large number of twins (MZ and DZ) were analyzed based on principal factors to evaluate genetic effects and common familial environmental influences on twin data by the use of maximum likelihood-based Variance decomposition analysis. Sample consists of monozygotic (MZ) twins of two sexes (102 male pairs and 138 female pairs) and 120 pairs of dizygotic (DZ) female twins. All asymmetry (DA and FA) and diversity of dermatoglyphic traits were clearly separated into factors. These are perfectly corroborated with the earlier studies in different ethnic populations, which indicate a common biological validity perhaps exists of the underlying component structures of dermatoglyphic characters. Our heritability result in twins clearly showed that DA_F2 is inherited mostly in dominant type (28.0%) and FA_F1 is additive (60.7%), but no significant difference in sexes was observed for these factors. Inheritance is also very prominent in diversity Factor 1, which is exactly corroborated with our previous findings. The present results are similar with the earlier results of finger ridge count diversity in twin data, which suggested that finger ridge count diversity is under genetic control.

Common Viral Integration Sites Identified in Avian Leukosis Virus-Induced B-Cell Lymphomas

PubMed Central

Justice, James F.; Morgan, Robin W.

2015-01-01

ABSTRACT Avian leukosis virus (ALV) induces B-cell lymphoma and other neoplasms in chickens by integrating within or near cancer genes and perturbing their expression. Four genes—MYC, MYB, Mir-155, and TERT—have previously been identified as common integration sites in these virus-induced lymphomas and are thought to play a causal role in tumorigenesis. In this study, we employ high-throughput sequencing to identify additional genes driving tumorigenesis in ALV-induced B-cell lymphomas. In addition to the four genes implicated previously, we identify other genes as common integration sites, including TNFRSF1A, MEF2C, CTDSPL, TAB2, RUNX1, MLL5, CXorf57, and BACH2. We also analyze the genome-wide ALV integration landscape in vivo and find increased frequency of ALV integration near transcriptional start sites and within transcripts. Previous work has shown ALV prefers a weak consensus sequence for integration in cultured human cells. We confirm this consensus sequence for ALV integration in vivo in the chicken genome. PMID:26670384

Antibiotics are the Most Commonly Identified Cause of Perioperative Hypersensitivity Reactions

PubMed Central

Kuhlen, James L.; Camargo, Carlos A.; Balekian, Diana S.; Blumenthal, Kimberly G.; Guyer, Autumn; Morris, Theresa; Long, Aidan; Banerji, Aleena

2016-01-01

Background Hypersensitivity reactions (HSR) during the perioperative period are unpredictable and can be life threatening. Prospective studies for evaluation of perioperative HSR are lacking and data on causative agents varies between different studies. Objective To prospectively determine the success of a comprehensive allergy evaluation plan for patients with HSR during anesthesia, including identification of causative agent and outcomes during subsequent anesthesia exposure. Methods All patients referred for perioperative HSR between November 2013 and March 2015, from a Boston teaching hospital, were evaluated using a standardized protocol with skin testing (ST) within 6 months of HSR. Comprehensive allergy evaluation included collection of patient information, including characteristics of HSR during anesthesia. We reviewed results of ST and/or test doses for all potential causative medications Event-related tryptase levels were reviewed when available. Results Over 17 months, 25 patients completed the comprehensive allergy evaluation. Fifty-two percent (13/25) were female with a median age of 52 (IQR 43–66) years. The most frequently observed HSR systems were cutaneous (68%), cardiovascular (64%), and pulmonary (24%). A culprit drug, defined as a positive ST, was identified in 36% (9/25) of patients. The most common agent identified was cefazolin (6/9). Following our comprehensive evaluation and management plan, seven (7/8, 88%) patients tolerated subsequent anesthesia. Conclusions Cefazolin was the most commonly identified cause of perioperative HSR in our study population. Skin testing patients within 6 months of a perioperative HSR may improve the odds of finding a positive result. Tolerance of subsequent anesthesia is generally achieved in patients undergoing our comprehensive evaluation. PMID:27039234

Endocrine disruptor induction of epigenetic transgenerational inheritance of disease.

PubMed

Skinner, Michael K

2014-12-01

Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Endocrine Disruptor Induction of Epigenetic Transgenerational Inheritance of Disease

PubMed Central

Skinner, Michael K.

2014-01-01

Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. PMID:25088466

Partnering in oncogenetic research--the INHERIT BRCAs experience: opportunities and challenges.

PubMed

Avard, Denise; Bridge, Peter; Bucci, Lucie M; Chiquette, Jocelyne; Dorval, Michel; Durocher, Francine; Easton, Doug; Godard, Béatrice; Goldgar, David; Knoppers, Bartha Maria; Laframboise, Rachel; Lespérance, Bernard; Plante, Marie; Tavtigian, Sean V; Vézina, Hélène; Wilson, Brenda; Simard, Jacques

2006-01-01

Today it is common to conduct research in collaboration with colleagues from different disciplines and institutions. The INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility (INHERIT BRCAs), involves Canadian and international experts from diverse fields working with health service providers, patients and collaborators from the World Health Organization and other European networks. Evidence-based information and knowledge transfer drive our efforts to advance genomic research to understand the genetic basis of cancer susceptibility and treatment response. Several goals reveal the interdisciplinary team approach: (a) to estimate the prevalence and penetrance of BRCA1 and BRCA2 mutations and their deleterious impact upon different populations; (b) to pinpoint novel breast cancer susceptibility loci; (c) to assess the efficacy of clinical interventions; (d) to address changes in quality of life and health-related behaviour from the decision to undergo genetics testing and during follow-up; (e) to evaluate legal, social and ethical implications; and, finally; (f) to promote professional and public education by facilitating the transfer of research findings to clinical practice and informing policy makers. The lessons learned by the INHERIT research team and future challenges are presented.

Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

PubMed

Tracey, Rebecca; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Skinner, Michael K

2013-04-01

Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. Copyright © 2012 Elsevier Inc. All rights reserved.

Hydrocarbons (Jet Fuel JP-8) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

PubMed Central

Tracey, Rebecca; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Skinner, Michael K.

2012-01-01

Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. PMID:23453003

Integrating common and rare genetic variation in diverse human populations.

PubMed

Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E

2010-09-02

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of

Utilizing inheritance in requirements engineering

NASA Technical Reports Server (NTRS)

Kaindl, Hermann

1994-01-01

The scope of this paper is the utilization of inheritance for requirements specification, i.e., the tasks of analyzing and modeling the domain, as well as forming and defining requirements. Our approach and the tool supporting it are named RETH (Requirements Engineering Through Hypertext). Actually, RETH uses a combination of various technologies, including object-oriented approaches and artificial intelligence (in particular frames). We do not attempt to exclude or replace formal representations, but try to complement and provide means for gradually developing them. Among others, RETH has been applied in the CERN (Conseil Europeen pour la Rechereche Nucleaire) Cortex project. While it would be impossible to explain this project in detail here, it should be sufficient to know that it deals with a generic distributed control system. Since this project is not finished yet, it is difficult to state its size precisely. In order to give an idea, its final goal is to substitute the many existing similar control systems at CERN by this generic approach. Currently, RETH is also tested using real-world requirements for the Pastel Mission Planning System at ESOC in Darmstadt. First, we outline how hypertext is integrated into a frame system in our approach. Moreover, the usefulness of inheritance is demonstrated as performed by the tool RETH. We then summarize our experiences of utilizing inheritance in the Cortex project. Lastly, RETH will be related to existing work.

Transgenerational epigenetic inheritance: how important is it?

PubMed Central

Grossniklaus, Ueli; Kelly, William G.; Ferguson-Smith, Anne C.; Pembrey, Marcus; Lindquist, Susan

2014-01-01

Much attention has been given to the idea of transgenerational epigenetic inheritance, but fundamental questions remain regarding how much takes place and the impact that this might have on organisms. We asked five leading researchers in this area — working on a range of model organisms and in human disease — for their views on these topics. Their responses highlight the mixture of excitement and caution that surrounds transgenerational epigenetic inheritance and the wide gulf between species in terms of our knowledge of the mechanisms that may be involved. PMID:23416892

Sex-linked inheritance of host-plant specialization in a polyphagous butterfly

PubMed Central

Janz, N.

1998-01-01

I investigated the genetic background of intraspecific variation in oviposition specificity in the generalist butterfly Polygonia c-album. Using reciprocal crosses between two populations that differ in their degree of specialization, I show that specificity is strongly sex-linked. This indicates that genes determining this difference are located primarily on the paternally inherited X-chromosome. The results suggest that intraspecific differences in specificity are caused by the same genetic mechanisms that have been shown to determine interspecific differences in host-plant ranking in other butterflies. Accordingly, the common assumption that specialization and ranking are determined by fundamentally different mechanisms was not supported.

Gene therapy for inherited retinal degenerations: initial successes and future challenges

NASA Astrophysics Data System (ADS)

Gupta, Priya R.; Huckfeldt, Rachel M.

2017-10-01

Inherited retinal degenerations are a clinically and genetically heterogeneous group of conditions that have historically shared an untreatable course. In recent years, however, a wide range of therapeutic strategies have demonstrated efficacy in preclinical studies and entered clinical trials with a common goal of improving visual function for patients affected with these conditions. Gene therapy offers a particularly elegant and precise opportunity to target the causative genetic mutations underlying these monogenic diseases. The present review will provide an overview of gene therapy with particular emphasis on key clinical results to date and challenges for the future.

Recent Progress in Genome Editing Approaches for Inherited Cardiovascular Diseases.

PubMed

Kaur, Balpreet; Perea-Gil, Isaac; Karakikes, Ioannis

2018-06-02

This review describes the recent progress in nuclease-based therapeutic applications for inherited heart diseases in vitro, highlights the development of the most recent genome editing technologies and discusses the associated challenges for clinical translation. Inherited cardiovascular disorders are passed from generation to generation. Over the past decade, considerable progress has been made in understanding the genetic basis of inherited heart diseases. The timely emergence of genome editing technologies using engineered programmable nucleases has revolutionized the basic research of inherited cardiovascular diseases and holds great promise for the development of targeted therapies. The genome editing toolbox is rapidly expanding, and new tools have been recently added that significantly expand the capabilities of engineered nucleases. Newer classes of versatile engineered nucleases, such as the "base editors," have been recently developed, offering the potential for efficient and precise therapeutic manipulation of the human genome.

Inheritance of microsatellite loci in the polyploid lake sturgeon (Acipenser fulvescens)

USGS Publications Warehouse

Pyatskowit, J.D.; Krueger, C.C.; Kincaid, H.L.; May, B.

2001-01-01

Inheritance in the expression of amplicons for four microsatellite primer pairs was determined using 10 families created from gametes of wild lake sturgeon (Acipenser fulvescens). Loci Afu34 and Afu68 expressed a maximum of two even-intensity bands per individual and had progeny genotype ratios that fit disomic inheritance (P > 0.05). Some variation exhibited at Afu34 and Afu68 was attributable to a null allele. Genotype expression at both loci also indicated that one female parent had transmitted unreduced gametes. Primer Afu39 amplified products that exhibited four gene doses, where genotype counts fit expected ratios for disomic inheritance (P > 0.05) indicating amplification of products from two disomic loci that share alleles. Meiotic drive was evident at the Afu39 loci based on a test for random segregation (P < 0.05). Only the expression of Afu19 gave evidence of tetrasomic inheritance based on a single progeny potentially produced by a double reduction gamete. No evidence for proposed octoploid inheritance was observed.

Inheritance-mode specific pathogenicity prioritization (ISPP) for human protein coding genes.

PubMed

Hsu, Jacob Shujui; Kwan, Johnny S H; Pan, Zhicheng; Garcia-Barcelo, Maria-Mercè; Sham, Pak Chung; Li, Miaoxin

2016-10-15

Exome sequencing studies have facilitated the detection of causal genetic variants in yet-unsolved Mendelian diseases. However, the identification of disease causal genes among a list of candidates in an exome sequencing study is still not fully settled, and it is often difficult to prioritize candidate genes for follow-up studies. The inheritance mode provides crucial information for understanding Mendelian diseases, but none of the existing gene prioritization tools fully utilize this information. We examined the characteristics of Mendelian disease genes under different inheritance modes. The results suggest that Mendelian disease genes with autosomal dominant (AD) inheritance mode are more haploinsufficiency and de novo mutation sensitive, whereas those autosomal recessive (AR) genes have significantly more non-synonymous variants and regulatory transcript isoforms. In addition, the X-linked (XL) Mendelian disease genes have fewer non-synonymous and synonymous variants. As a result, we derived a new scoring system for prioritizing candidate genes for Mendelian diseases according to the inheritance mode. Our scoring system assigned to each annotated protein-coding gene (N = 18 859) three pathogenic scores according to the inheritance mode (AD, AR and XL). This inheritance mode-specific framework achieved higher accuracy (area under curve  = 0.84) in XL mode. The inheritance-mode specific pathogenicity prioritization (ISPP) outperformed other well-known methods including Haploinsufficiency, Recessive, Network centrality, Genic Intolerance, Gene Damage Index and Gene Constraint scores. This systematic study suggests that genes manifesting disease inheritance modes tend to have unique characteristics. ISPP is included in KGGSeq v1.0 (http://grass.cgs.hku.hk/limx/kggseq/), and source code is available from (https://github.com/jacobhsu35/ISPP.git). mxli@hku.hkSupplementary information: Supplementary data are available at Bioinformatics online. © The Author

Genetics of host plant use and life history in the comma butterfly across Europe: varying modes of inheritance as a potential reproductive barrier.

PubMed

Nygren, G H; Nylin, S; Stefanescu, C

2006-11-01

Comma butterflies (Nymphalidae: Polygonia c-album L.) from one Belgian site and three Spanish sites were crossed with butterflies from a Swedish population in order to investigate inheritance of female host plant choice, egg mass and larval growth rate. We found three different modes of inheritance for the three investigated traits. In line with earlier results from crosses between Swedish and English populations, the results regarding female oviposition preference (choice between Urtica dioica and Salix caprea) showed X-linked inheritance to be of importance for the variation between Sweden and the other sites. Egg mass and growth rate did not show any sex-linked inheritance. Egg mass differences between populations seem to be controlled mainly by additive autosomal genes, as hybrids showed intermediate values. The growth rates of both hybrid types following reciprocal crossings were similar to each other but consistently higher than for the two source populations, suggesting a nonadditive mode of inheritance which is not sex-linked. The different modes of inheritance for host plant preference vs. important life history traits are likely to result in hybrids with unfit combinations of traits. This type of potential reproductive barrier based on multiple ecologically important traits deserves more attention, as it should be a common situation for instance in the early stages of population divergence in host plant usage, facilitating ecological speciation.

Integrity of the yeast mitochondrial genome, but not its distribution and inheritance, relies on mitochondrial fission and fusion

PubMed Central

Osman, Christof; Noriega, Thomas R.; Okreglak, Voytek; Fung, Jennifer C.; Walter, Peter

2015-01-01

Mitochondrial DNA (mtDNA) is essential for mitochondrial and cellular function. In Saccharomyces cerevisiae, mtDNA is organized in nucleoprotein structures termed nucleoids, which are distributed throughout the mitochondrial network and are faithfully inherited during the cell cycle. How the cell distributes and inherits mtDNA is incompletely understood although an involvement of mitochondrial fission and fusion has been suggested. We developed a LacO-LacI system to noninvasively image mtDNA dynamics in living cells. Using this system, we found that nucleoids are nonrandomly spaced within the mitochondrial network and observed the spatiotemporal events involved in mtDNA inheritance. Surprisingly, cells deficient in mitochondrial fusion and fission distributed and inherited mtDNA normally, pointing to alternative pathways involved in these processes. We identified such a mechanism, where we observed fission-independent, but F-actin–dependent, tip generation that was linked to the positioning of mtDNA to the newly generated tip. Although mitochondrial fusion and fission were dispensable for mtDNA distribution and inheritance, we show through a combination of genetics and next-generation sequencing that their absence leads to an accumulation of mitochondrial genomes harboring deleterious structural variations that cluster at the origins of mtDNA replication, thus revealing crucial roles for mitochondrial fusion and fission in maintaining the integrity of the mitochondrial genome. PMID:25730886

Genotype and phenotype relationships in 10 Pakistani unrelated patients with inherited factor VII deficiency.

PubMed

Borhany, M; Boijout, H; Pellequer, J-L; Shamsi, T; Moulis, G; Aguilar-Martinez, P; Schved, J-F; Giansily-Blaizot, M

2013-11-01

Inherited factor VII (FVII) deficiency is one of the commonest rare bleeding disorders. It is characterized by a wide molecular and clinical heterogeneity and an autosomal recessive pattern of inheritance. Factor VII-deficient patients are still scarcely explored in Pakistan although rare bleeding disorders became quite common as a result of traditional consanguineous marriages. The aim of the study was to give a first insight of F7 gene mutations in Pakistani population. Ten unrelated FVII-deficient patients living in Pakistan were investigated (median FVII:C = 2%; range = 2-37%). A clinical questionnaire was filled out for each patient and direct sequencing was performed on the coding regions, intron/exon boundaries and 5' and 3' untranslated regions of the F7 gene. Nine different mutations (eight missense mutations and one located within the F7 promoter) were identified on the F7 gene. Five of them were novel (p.Cys82Tyr, p.Cys322Ser, p.Leu357Phe, p.Thr410Ala, c-57C>T, the last being predicted to alter the binding site of transcription factor HNF-4). Half of the patients had single mutations in Cys residues involved in disulfide bridges. The p.Cys82Arg mutation was the most frequent in our series. Six of seven patients with FVII:C levels below 10% were homozygous in connection with the high percentage of consanguinity in our series. In addition, we graded the 10 patients according to three previously published classifications for rare bleeding disorders. The use of the bleeding score proposed by Tosetto and co-workers in 2006 appears to well qualify the bleeding tendency in our series. © 2013 John Wiley & Sons Ltd.

Genetic engineering and therapy for inherited and acquired cardiomyopathies.

PubMed

Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

2006-10-01

The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

"You're saying something by giving things to them:" communication and family inheritance.

PubMed

de Witt, Lorna; Campbell, Lori; Ploeg, Jenny; Kemp, Candace L; Rosenthal, Carolyn

2013-09-01

The study purpose was to contribute to a more complete understanding of the experience and meaning of family inheritance. The aim of this article is to describe and discuss the meaning of communication in inheritance experiences among Canadian families. A constructivist/interpretive methodological approach guided this research. Participants were recruited through purposive, convenience sampling from two cities and one town in southern and southwestern Ontario, Canada. Fifty face-to-face, semi-structured, audio-taped, in-depth interviews were conducted between June 2006 and April 2007. NVivo software was used to organize and analyze the data. A content analysis method guided data analysis. Participants interpreted the meaning of family structure, relationships, feelings, and past inheritance experiences to construct their family inheritance communication. Analysis of the findings revealed four themes regarding the role of communication in family inheritance including: (a) avoiding conflict and preserving biological ties , (b) resisting conversations about possessions , (c) achieving confidence with possession communication , and (d) lasting effects. Participants from non-blended and blended families experienced similar inheritance communication challenges related to past experience with their parents' wills and distribution of their own possessions. Participants with past positive inheritance experiences with parents adopted similar strategies when communicating their own inheritance wishes. Negative messages conveyed to participants by their parent's wills inspired participants to communicate in opposite ways in their own inheritance planning. The study findings are useful for gerontologists, lawyers, family counselors, and estate planners.

Interpreting phenotypic antibiotic tolerance and persister cells as evolution via epigenetic inheritance.

PubMed

Day, Troy

2016-04-01

Epigenetic inheritance is the transmission of nongenetic material such as gene expression levels, RNA and other biomolecules from parents to offspring. There is a growing realization that such forms of inheritance can play an important role in evolution. Bacteria represent a prime example of epigenetic inheritance because a large array of cellular components is transmitted to offspring, in addition to genetic material. Interestingly, there is an extensive and growing empirical literature showing that many bacteria can form 'persister' cells that are phenotypically resistant or tolerant to antibiotics, but most of these results are not interpreted within the context of epigenetic inheritance. Instead, persister cells are usually viewed as a genetically encoded bet-hedging strategy that has evolved in response to a fluctuating environment. Here I show, using a relatively simple model, that many of these empirical findings can be more simply understood as arising from a combination of epigenetic inheritance and cellular noise. I therefore suggest that phenotypic drug tolerance in bacteria might represent one of the best-studied examples of evolution under epigenetic inheritance. © 2016 John Wiley & Sons Ltd.

Next-generation sequencing to solve complex inherited retinal dystrophy: A case series of multiple genes contributing to disease in extended families.

PubMed

Jones, Kaylie D; Wheaton, Dianna K; Bowne, Sara J; Sullivan, Lori S; Birch, David G; Chen, Rui; Daiger, Stephen P

2017-01-01

With recent availability of next-generation sequencing (NGS), it is becoming more common to pursue disease-targeted panel testing rather than traditional sequential gene-by-gene dideoxy sequencing. In this report, we describe using NGS to identify multiple disease-causing mutations that contribute concurrently or independently to retinal dystrophy in three relatively small families. Family members underwent comprehensive visual function evaluations, and genetic counseling including a detailed family history. A preliminary genetic inheritance pattern was assigned and updated as additional family members were tested. Family 1 (FAM1) and Family 2 (FAM2) were clinically diagnosed with retinitis pigmentosa (RP) and had a suspected autosomal dominant pedigree with non-penetrance (n.p.). Family 3 (FAM3) consisted of a large family with a diagnosis of RP and an overall dominant pedigree, but the proband had phenotypically cone-rod dystrophy. Initial genetic analysis was performed on one family member with traditional Sanger single gene sequencing and/or panel-based testing, and ultimately, retinal gene-targeted NGS was required to identify the underlying cause of disease for individuals within the three families. Results obtained in these families necessitated further genetic and clinical testing of additional family members to determine the complex genetic and phenotypic etiology of each family. Genetic testing of FAM1 (n = 4 affected; 1 n.p.) identified a dominant mutation in RP1 (p.Arg677Ter) that was present for two of the four affected individuals but absent in the proband and the presumed non-penetrant individual. Retinal gene-targeted NGS in the fourth affected family member revealed compound heterozygous mutations in USH2A (p. Cys419Phe, p.Glu767Serfs*21). Genetic testing of FAM2 (n = 3 affected; 1 n.p.) identified three retinal dystrophy genes ( PRPH2 , PRPF8 , and USH2A ) with disease-causing mutations in varying combinations among the affected family members

High glucose intake and glycaemic level in critically ill neonates with inherited metabolic disorders of intoxication.

PubMed

Grimaud, Marion; de Lonlay, Pascale; Dupic, Laurent; Arnoux, Jean-Baptiste; Brassier, Anais; Hubert, Philippe; Lesage, Fabrice; Oualha, Mehdi

2016-06-01

To investigate glycaemic levels in critically ill neonates with inherited metabolic disorders of intoxication. Thirty-nine neonates with a median age of 7 days (0-24) were retrospectively included (urea cycle disorders (n = 18), maple syrup disease (n = 13), organic acidemias (n = 8)). Twenty-seven neonates were intubated, 21 were haemodialysed and 6 died. During the first 3 days, median total and peak blood glucose (BG) levels were 7.1 mmol/L (0.9-50) and 10 mmol/L (5.1-50), respectively. The median glucose intake rate was 11 mg/kg/min (2.7-15.9). Fifteen and 23 neonates exhibited severe hyperglycaemia (≥2 BG levels >12 mmol/L) and mild hyperglycaemia (≥2 BG levels >7 and ≤12 mmol/L), respectively. Glycaemic levels and number of hyperglycaemic neonates decreased over the first 3 days (p < 0.001) while total glucose intake rate was stable (p = 0.11). Enteral route of glucose intake was associated with a lower number of hyperglycaemic neonates (p = 0.04) and glycaemic level (p = 0.02). Hyperglycaemia is common in critically ill neonates receiving high glucose intake with inherited metabolic disorders of intoxication. Physicians should decrease the rate of total glucose intake and begin enteral feeding as quickly as possible in cases of persistent hyperglycaemia. • The risk of hyperglycaemia in the acute phase of critical illness is high. What is New: • Hyperglycaemia is common in the initial management of critically ill neonates with inherited metabolic disorders of intoxication receiving high glucose intake.

Antibiotics Are the Most Commonly Identified Cause of Perioperative Hypersensitivity Reactions.

PubMed

Kuhlen, James L; Camargo, Carlos A; Balekian, Diana S; Blumenthal, Kimberly G; Guyer, Autumn; Morris, Theresa; Long, Aidan; Banerji, Aleena

2016-01-01

Hypersensitivity reactions (HSRs) during the perioperative period are unpredictable and can be life threatening. Prospective studies for the evaluation of perioperative HSRs are lacking, and data on causative agents vary between different studies. The objective of this study was to prospectively determine the success of a comprehensive allergy evaluation plan for patients with HSRs during anesthesia, including identification of a causative agent and outcomes during subsequent anesthesia exposure. All patients referred for a perioperative HSR between November 2013 and March 2015, from a Boston teaching hospital, were evaluated using a standardized protocol with skin testing (ST) within 6 months of HSR. Comprehensive allergy evaluation included collection of patient information, including characteristics of HSR during anesthesia. We reviewed the results of ST and/or test doses for all potential causative medications Event-related tryptase levels were reviewed when available. Over 17 months, 25 patients completed the comprehensive allergy evaluation. Fifty-two percent (13 of 25) were female with a median age of 52 (interquartile range 43-66) years. The most frequently observed HSR systems were cutaneous (68%), cardiovascular (64%), and pulmonary (24%). A culprit drug, defined as a positive ST, was identified in 36% (9 of 25) of patients. The most common agent identified was cefazolin (6 of 9). After our comprehensive evaluation and management plan, 7 (7 of 8, 88%) patients tolerated subsequent anesthesia. Cefazolin was the most commonly identified cause of a perioperative HSR in our study population. Skin testing patients within 6 months of a perioperative HSR may improve the odds of finding a positive result. Tolerance of subsequent anesthesia is generally achieved in patients undergoing our comprehensive evaluation. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

PubMed Central

Toledo, Sergio P. A.; Lourenço, Delmar M.; Toledo, Rodrigo A.

2013-01-01

Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed. PMID:23917672

Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

PubMed Central

Beilina, Alexandria; Rudenko, Iakov N.; Kaganovich, Alice; Civiero, Laura; Chau, Hien; Kalia, Suneil K.; Kalia, Lorraine V.; Lobbestael, Evy; Chia, Ruth; Ndukwe, Kelechi; Ding, Jinhui; Nalls, Mike A.; Olszewski, Maciej; Hauser, David N.; Kumaran, Ravindran; Lozano, Andres M.; Baekelandt, Veerle; Greene, Lois E.; Taymans, Jean-Marc; Greggio, Elisa; Cookson, Mark R.; Nalls, Mike A.; Plagnol, Vincent; Martinez, Maria; Hernandez, Dena G; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M A; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M; Brockmann, Kathrin; Brooks, Janet; Burn, David J; Charlesworth, Gavin; Chen, Honglei; Chong, Sean; Clarke, Carl E; Cookson, Mark R; Cooper, J Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T; van Dijk, Karin D; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gibbs, J Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Harris, Clare; van Hilten, Jacobus J; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E; Huttenlocher, Johanna; Illig, Thomas; München, Helmholtz Zentrum; Jónsson, Pálmi V; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; München, Helmholtz Zentrum; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R; Morrison, Karen E; Mudanohwo, Ese; O’Sullivan, Sean S; Pearson, Justin; Perlmutter, Joel S; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C A; Stefánsson, Hreinn; Steinberg, Stacy; Stockton, Joanna D; Strange, Amy; Talbot, Kevin; Tanner, Carlie M; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J; Uitterlinden, André G; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B; Wood, Nicholas W; Chinnery, Patrick F; Arepalli, Sampath; Cookson, Mark R; Dillman, Allissa; Ferrucci, Luigi; Gibbs, J Raphael; Hernandez, Dena G; Johnson, Robert; Longo, Dan L; Majounie, Elisa; Nalls, Michael A; O’Brien, Richard; Singleton, Andrew B; Traynor, Bryan J; Troncoso, Juan; van der Brug, Marcel; Zielke, H Ronald; Zonderman, Alan B

2014-01-01

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein–protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G–associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy–lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms. PMID:24510904

TBX6 Null Variants and a Common Hypomorphic Allele in Congenital Scoliosis

PubMed Central

Wu, N.; Ming, X.; Xiao, J.; Wu, Z.; Chen, X.; Shinawi, M.; Shen, Y.; Yu, G.; Liu, J.; Xie, H.; Gucev, Z.S.; Liu, S.; Yang, N.; Al-Kateb, H.; Chen, J.; Zhang, Jian; Hauser, N.; Zhang, T.; Tasic, V.; Liu, P.; Su, X.; Pan, X.; Liu, C.; Wang, L.; Shen, Joseph; Shen, Jianxiong; Chen, Y.; Zhang, T.; Zhang, Jianguo; Choy, K.W.; Wang, Jun; Wang, Q.; Li, S.; Zhou, W.; Guo, J.; Wang, Y.; Zhang, C.; Zhao, H.; An, Y.; Zhao, Y.; Wang, Jiucun; Liu, Z.; Zuo, Y.; Tian, Y.; Weng, X.; Sutton, V.R.; Wang, H.; Ming, Y.; Kulkarni, S.; Zhong, T.P.; Giampietro, P.F.; Dunwoodie, S.L.; Cheung, S.W.; Zhang, X.; Jin, L.; Lupski, J.R.; Qiu, G.; Zhang, F.

2015-01-01

BACKGROUND Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis. METHODS We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multi-center series of 42 persons with 16p11.2 deletions. RESULTS We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10−6). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10−6). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis. CONCLUSIONS Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. PMID:25564734

Inheritance of evolved clethodim resistance in Lolium rigidum populations from Australia.

PubMed

Saini, Rupinder Kaur; Malone, Jenna; Gill, Gurjeet; Preston, Christopher

2017-08-01

In Australia, the extensive use of clethodim for the control of Lolium rigidum has resulted in the evolution of many clethodim-resistant L. rigidum populations. Five clethodim-resistant populations of L. rigidum were analysed for the inheritance of clethodim resistance. Reciprocal crosses were made between resistant (R) and susceptible (S) populations. Within crosses, dose-responses of reciprocal F 1 families of all populations except A61 were similar to each other, indicating that clethodim resistance in these populations is encoded on the nuclear genome. The level of dominance observed in the dose-response experiments ranged from partial to complete within the herbicide rate used. In the A61 population, within each cross, the response of F 1 from the maternal and paternal parent was different, indicating that resistance is inherited through the female parent. All backcross populations segregated in a different manner. Only one population, FP, fitted a single-gene model (1:1). Two populations fitted two-gene models: a 3:1 inheritance model for F4 and a 1:3 inheritance model for A91. For population E2, no clear pattern of inheritance was determined, suggesting more complex inheritance. The results of this study indicate that different patterns of clethodim resistance in L. rigidum exist. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Inherited Representations are Read in Development

PubMed Central

Shea, Nicholas

2013-01-01

Recent theoretical work has identified a tightly constrained sense in which genes carry representational content. Representational properties of the genome are founded in the transmission of DNA over phylogenetic time and its role in natural selection. However, genetic representation is not just relevant to questions of selection and evolution. This article goes beyond existing treatments and argues for the heterodox view that information generated by a process of selection over phylogenetic time can be read in ontogenetic time, in the course of individual development. Recent results in evolutionary biology, drawn both from modelling work, and from experimental and observational data, support a role for genetic representation in explaining individual ontogeny: both genetic representations and environmental information are read by the mechanisms of development, in an individual, so as to lead to adaptive phenotypes. Furthermore, in some cases there appears to have been selection between individuals that rely to different degrees on the two sources of information. Thus, the theory of representation in inheritance systems like the genome is much more than just a coherent reconstruction of information talk in biology. Genetic representation is a property with considerable explanatory utility. 1 Introduction2 Inherited Representations3 Reading Genetic Representations   3.1 Do genes carry correlational information?4 Selection Between Genetic and Environmental Information   4.1 Modelling  4.2 Empirical applications  4.3 Maternal effects5 Genetic Representation and the Genome   5.1 Information capacity of organisms' genomes  5.2 Many amino acids, few nucleotides  5.3 A function of sex6 Explaining Further Aspects of Development   6.1 Canalization against environmental variation  6.2 An informational function for the nuclear membrane?7 Conclusion PMID:23526835

Archean inheritance in zircon from late Paleozoic granites from the Avalon zone of southeastern New England: an African connection

USGS Publications Warehouse

Zartman, R.E.; Don, Hermes O.

1987-01-01

In southeastern New England the Narragansett Pier Granite locally intrudes Carboniferous metasedimentary rocks of the Narragansett basin, and yields a monazite UPb Permian emplacement age of 273 ?? 2 Ma. Zircon from the Narragansett Pier Granite contains a minor but detectable amount of an older, inherited component, and shows modern loss of lead. Zircon from the late-stage, aplitic Westerly Granite exhibits a more pronounced lead inheritance -permitting the inherited component to be identified as Late Archean. Such old relict zircon has not been previously recognized in Proterozoic to Paleozoic igneous rocks in New England, and may be restricted to late Paleozoic rocks of the Avalon zone. We suggest that the Archean crustal component reflects an African connection, in which old Archean crust was underplated to the Avalon zone microplate in the late Paleozoic during collision of Gondwanaland with Avalonia. ?? 1987.

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.

PubMed

Dunlop, Malcolm G; Dobbins, Sara E; Farrington, Susan Mary; Jones, Angela M; Palles, Claire; Whiffin, Nicola; Tenesa, Albert; Spain, Sarah; Broderick, Peter; Ooi, Li-Yin; Domingo, Enric; Smillie, Claire; Henrion, Marc; Frampton, Matthew; Martin, Lynn; Grimes, Graeme; Gorman, Maggie; Semple, Colin; Ma, Yusanne P; Barclay, Ella; Prendergast, James; Cazier, Jean-Baptiste; Olver, Bianca; Penegar, Steven; Lubbe, Steven; Chander, Ian; Carvajal-Carmona, Luis G; Ballereau, Stephane; Lloyd, Amy; Vijayakrishnan, Jayaram; Zgaga, Lina; Rudan, Igor; Theodoratou, Evropi; Starr, John M; Deary, Ian; Kirac, Iva; Kovacević, Dujo; Aaltonen, Lauri A; Renkonen-Sinisalo, Laura; Mecklin, Jukka-Pekka; Matsuda, Koichi; Nakamura, Yusuke; Okada, Yukinori; Gallinger, Steven; Duggan, David J; Conti, David; Newcomb, Polly; Hopper, John; Jenkins, Mark A; Schumacher, Fredrick; Casey, Graham; Easton, Douglas; Shah, Mitul; Pharoah, Paul; Lindblom, Annika; Liu, Tao; Smith, Christopher G; West, Hannah; Cheadle, Jeremy P; Midgley, Rachel; Kerr, David J; Campbell, Harry; Tomlinson, Ian P; Houlston, Richard S

2012-05-27

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Social and Experiential Influences on the Development of Inheritance Concepts

ERIC Educational Resources Information Center

Williams, Joanne M.; Smith, Lesley A.

2006-01-01

This study explored social and experiential differences in children's (aged 4 to 14 years) concepts of inheritance. The study utilized semi-structured interviews including four tasks that were designed to elicit judgements and explanations about different aspects of inheritance understanding. A variety of social and experiential factors were…

"That's not how we do it": managing the inherited medical practice team.

PubMed

Hills, Laura

2013-01-01

Most medical practice managers who take a new job will inherit an existing team. Those first few days on the job are critical because they can determine whether or not the new manager will succeed. This article provides a game plan for new medical practice managers so they get off on the right foot with their inherited teams. It suggests strategies for learning about the team's culture and for demonstrating visibly that there is a new manager in the job. It offers guidelines about introducing the new manager to the inherited team, discussing past experiences, and establishing new expectations. This article further provides practical tips for serving as a role model, gaining allies, and dealing with troublemakers quickly and effectively. It suggests strategies for speaking about the previous practice manager and for creating excitement with the inherited team. Finally, this article offers a set of 15 questions a new manager can ask members of the inherited team to get to know them, an additional 25-point team assessment instrument, and a step-by-step strategy for raising the bar for mediocre, lackluster, or dysfunctional inherited teams.

OVAS: an open-source variant analysis suite with inheritance modelling.

PubMed

Mozere, Monika; Tekman, Mehmet; Kari, Jameela; Bockenhauer, Detlef; Kleta, Robert; Stanescu, Horia

2018-02-08

The advent of modern high-throughput genetics continually broadens the gap between the rising volume of sequencing data, and the tools required to process them. The need to pinpoint a small subset of functionally important variants has now shifted towards identifying the critical differences between normal variants and disease-causing ones. The ever-increasing reliance on cloud-based services for sequence analysis and the non-transparent methods they utilize has prompted the need for more in-situ services that can provide a safer and more accessible environment to process patient data, especially in circumstances where continuous internet usage is limited. To address these issues, we herein propose our standalone Open-source Variant Analysis Sequencing (OVAS) pipeline; consisting of three key stages of processing that pertain to the separate modes of annotation, filtering, and interpretation. Core annotation performs variant-mapping to gene-isoforms at the exon/intron level, append functional data pertaining the type of variant mutation, and determine hetero/homozygosity. An extensive inheritance-modelling module in conjunction with 11 other filtering components can be used in sequence ranging from single quality control to multi-file penetrance model specifics such as X-linked recessive or mosaicism. Depending on the type of interpretation required, additional annotation is performed to identify organ specificity through gene expression and protein domains. In the course of this paper we analysed an autosomal recessive case study. OVAS made effective use of the filtering modules to recapitulate the results of the study by identifying the prescribed compound-heterozygous disease pattern from exome-capture sequence input samples. OVAS is an offline open-source modular-driven analysis environment designed to annotate and extract useful variants from Variant Call Format (VCF) files, and process them under an inheritance context through a top-down filtering schema of

Genetic Testing for Inherited Heart Disease

MedlinePlus

... are also inherited heart conditions that affect the electric system of the heart, causing abnormal heart rhythms ... mistakenly labeled as a heart attack, drowning, or car accident. The sudden death of a previously healthy ...

Inheritance of restriction fragment length polymorphisms, random amplified polymorphic DNAs and isozymes in coastal Douglas-fir

Treesearch

K.D. Jermstad; A.M. Reem; J.R. Henifin; N.C. Wheeler; D.B Neale

1994-01-01

A total of 225 new genetic loci [151 restriction fragment length polymorphisms (RFLP) and 74 random amplified polymorphic DNAs (RAPD)] in coastal Douglas- fir [Pseudotsuga menziesii (Mirb.) Franco var. menziesii] have been identified using a three-generation outbred pedigree. The Mendelian inheritance of 16 RFLP loci and 29...

Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6.

PubMed

Hill, Joshua A; Magaret, Amalia S; Hall-Sedlak, Ruth; Mikhaylova, Anna; Huang, Meei-Li; Sandmaier, Brenda M; Hansen, John A; Jerome, Keith R; Zerr, Danielle M; Boeckh, Michael

2017-08-24

Human herpesvirus 6 (HHV-6) species have a unique ability to integrate into chromosomal telomeres. Mendelian inheritance via gametocyte integration results in HHV-6 in every nucleated cell. The epidemiology and clinical effect of inherited chromosomally integrated HHV-6 (iciHHV-6) in hematopoietic cell transplant (HCT) recipients is unclear. We identified 4319 HCT donor-recipient pairs (8638 subjects) who received an allogeneic HCT and had archived pre-HCT peripheral blood mononuclear cell samples. We screened these samples for iciHHV-6 and compared characteristics of HCT recipients and donors with iciHHV-6 with those of recipients and donors without iciHHV-6, respectively. We calculated Kaplan-Meier probability estimates and Cox proportional hazards models for post-HCT outcomes based on recipient and donor iciHHV-6 status. We identified 60 HCT recipients (1.4%) and 40 donors (0.9%) with iciHHV-6; both recipient and donor harbored iciHHV-6 in 13 HCTs. Thus, there were 87 HCTs (2%) in which the recipient, donor, or both harbored iciHHV-6. Acute graft-versus-host disease (GVHD) grades 2-4 was more frequent when recipients or donors had iciHHV-6 (adjusted hazard ratios, 1.7-1.9; P = .004-.001). Cytomegalovirus viremia (any and high-level) was more frequent among recipients with iciHHV-6 (adjusted HRs, 1.7-3.1; P = .001-.040). Inherited ciHHV-6 status did not significantly affect risk for chronic GVHD, hematopoietic cell engraftment, overall mortality, or nonrelapse mortality. Screening for iciHHV-6 could guide donor selection and post-HCT risk stratification and treatment. Further study is needed to replicate these findings and identify potential mechanisms. © 2017 by The American Society of Hematology.

Exome analysis of Smith-Magenis-like syndrome cohort identifies de novo likely pathogenic variants.

PubMed

Berger, Seth I; Ciccone, Carla; Simon, Karen L; Malicdan, May Christine; Vilboux, Thierry; Billington, Charles; Fischer, Roxanne; Introne, Wendy J; Gropman, Andrea; Blancato, Jan K; Mullikin, James C; Gahl, William A; Huizing, Marjan; Smith, Ann C M

2017-04-01

Smith-Magenis syndrome (SMS), a neurodevelopmental disorder characterized by dysmorphic features, intellectual disability (ID), and sleep disturbances, results from a 17p11.2 microdeletion or a mutation in the RAI1 gene. We performed exome sequencing on 6 patients with SMS-like phenotypes but without chromosomal abnormalities or RAI1 variants. We identified pathogenic de novo variants in two cases, a nonsense variant in IQSEC2 and a missense variant in the SAND domain of DEAF1, and candidate de novo missense variants in an additional two cases. One candidate variant was located in an alpha helix of Necdin (NDN), phased to the paternally inherited allele. NDN is maternally imprinted within the 15q11.2 Prader-Willi Syndrome (PWS) region. This can help clarify NDN's role in the PWS phenotype. No definitive pathogenic gene variants were detected in the remaining SMS-like cases, but we report our findings for future comparison. This study provides information about the inheritance pattern and recurrence risk for patients with identified variants and demonstrates clinical and genetic overlap of neurodevelopmental disorders. Identification and characterization of ID-related genes that assist in development of common developmental pathways and/or gene-networks, may inform disease mechanism and treatment strategies.

Guiametabolica.org: empowerment through internet tools in inherited metabolic diseases.

PubMed

Armayones, Manuel; Vilaseca, M Antònia; Cutillas, Júlia; Fàbrega, Jordi; Fernández, Jorge Juan; García, Mei; Egea, Natàlia; Pousada, Modesta; Gómez-Zuñiga, Beni; Pérez-Payarols, Jaume; Artuch, Rafael; Palau, Francesc; Serrano, Mercedes

2012-08-21

Web-based interventions are effective on the patient empowerment. Guiametabolica.org constitutes an interface for people involved in inherited metabolic diseases, trying to facilitate access to information and contact with professionals and other patients, offering a platform to develop support groups. Guiametabolica.org is widely considered for Spanish-speaking patients and caregivers with inherited metabolic diseases. Preliminary evaluations show changes in their habits, decrease in their senses of isolation and improvement regarding self-efficacy. Specific inherited metabolic diseases websites, especially participative websites, should be considered as a complement to more traditional clinical approaches. Their contribution lies in patient's general well-being, without interfering with traditional care.

Mitochondrial inheritance in budding yeasts: towards an integrated understanding.

PubMed

Solieri, Lisa

2010-11-01

Recent advances in yeast mitogenomics have significantly contributed to our understanding of the diversity of organization, structure and topology in the mitochondrial genome of budding yeasts. In parallel, new insights on mitochondrial DNA (mtDNA) inheritance in the model organism Saccharomyces cerevisiae highlighted an integrated scenario where recombination, replication and segregation of mtDNA are intricately linked to mitochondrial nucleoid (mt-nucleoid) structure and organelle sorting. In addition to this, recent discoveries of bifunctional roles of some mitochondrial proteins have interesting implications on mito-nuclear genome interactions and the relationship between mtDNA inheritance, yeast fitness and speciation. This review summarizes the current knowledge on yeast mitogenomics, mtDNA inheritance with regard to mt-nucleoid structure and organelle dynamics, and mito-nuclear genome interactions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Chloroplast and mitochondrial DNA are paternally inherited in Sequoia sempervirens D. Don Endl

PubMed Central

Neale, David B.; Marshall, Kimberly A.; Sederoff, Ronald R.

1989-01-01

Restriction fragment length polymorphisms in controlled crosses were used to infer the mode of inheritance of chloroplast DNA and mitochondrial DNA in coast redwood (Sequoia sempervirens D. Don Endl.). Chloroplast DNA was paternally inherited, as is true for all other conifers studied thus far. Surprisingly, a restriction fragment length polymorphism detected by a mitochondrial probe was paternally inherited as well. This polymorphism could not be detected in hybridizations with chloroplast probes covering the entire chloroplast genome, thus providing evidence that the mitochondrial probe had not hybridized to chloroplast DNA on the blot. We conclude that mitochondrial DNA is paternally inherited in coast redwood. To our knowledge, paternal inheritance of mitochondrial DNA in sexual crosses of a multicellular eukaryotic organism has not been previously reported. Images PMID:16594091

CULTURAL INHERITANCE OF SONG AND ITS ROLE IN THE EVOLUTION OF DARWIN'S FINCHES.

PubMed

Grant, B Rosemary; Grant, Peter R

1996-12-01

Songs of Darwin's finches were studied on the Galápagos Island of Daphne Major from 1976 to 1995. A single, structurally simple, and unvarying song is sung throughout life by each male of the two common species, Geospiza fortis (medium ground finch) and G. scandens (cactus finch). Songs of the two species differ strongly in quantitative features, and individual variation among males is much broader in G. fortis than in G. scandens. Although there are exceptions, songs of sons strongly resemble the songs of their fathers. They also resemble the songs of their paternal grandfathers, but not their maternal grandfathers, indicating that they are culturally inherited and not genetically inherited. Female G. fortis display a tendency to avoid mating with males that sing the same type of song as their father. They also avoid mating with males that sing heterospecific song, with very rare exceptions. Thus song, an evolving, culturally inherited trait, is an important factor in species recognition and mate choice. It constrains the mating of females to conspecifics, even when there is no genetic penalty to interbreeding, and thus may play a crucial role in species formation by promoting genetic isolation on secondary contact. The barrier is leaky in that occasional errors in song transmission result in misimprinting, which leads to a low incidence of hybridization and introgression. Introgression slows the rate of postzygotic isolation, but can produce individuals in novel genetic and morphological space that can provide the starting point of a new evolutionary trajectory. © 1996 The Society for the Study of Evolution.

Sexual conflict explains the extraordinary diversity of mechanisms regulating mitochondrial inheritance.

PubMed

Radzvilavicius, Arunas L; Lane, Nick; Pomiankowski, Andrew

2017-10-26

Mitochondria are predominantly inherited from the maternal gamete, even in unicellular organisms. Yet an extraordinary array of mechanisms enforce uniparental inheritance, which implies shifting selection pressures and multiple origins. We consider how this high turnover in mechanisms controlling uniparental inheritance arises using a novel evolutionary model in which control of mitochondrial transmission occurs either during spermatogenesis (by paternal nuclear genes) or at/after fertilization (by maternal nuclear genes). The model treats paternal leakage as an evolvable trait. Our evolutionary analysis shows that maternal control consistently favours strict uniparental inheritance with complete exclusion of sperm mitochondria, whereas some degree of paternal leakage of mitochondria is an expected outcome under paternal control. This difference arises because mito-nuclear linkage builds up with maternal control, allowing the greater variance created by asymmetric inheritance to boost the efficiency of purifying selection and bring benefits in the long term. In contrast, under paternal control, mito-nuclear linkage tends to be much weaker, giving greater advantage to the mixing of cytotypes, which improves mean fitness in the short term, even though it imposes a fitness cost to both mating types in the long term. Sexual conflict is an inevitable outcome when there is competition between maternal and paternal control of mitochondrial inheritance. If evolution has led to complete uniparental inheritance through maternal control, it creates selective pressure on the paternal nucleus in favour of subversion through paternal leakage, and vice versa. This selective divergence provides a reason for the repeated evolution of novel mechanisms that regulate the transmission of paternal mitochondria, both in the fertilized egg and spermatogenesis. Our analysis suggests that the widespread occurrence of paternal leakage and prevalence of heteroplasmy are natural outcomes of

Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss

PubMed Central

Kolte, Astrid M.; Nielsen, Henriette S.; Steffensen, Rudi; Crespi, Bernard; Christiansen, Ole B.

2015-01-01

Background and objectives: The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex. It has been associated with both beneficial and detrimental effects, consistent with antagonistic pleiotropy. It has also been proposed that the survival of long, conserved haplotypes may be due to gestational drive, i.e. selective miscarriage of fetuses who have not inherited the haplotype from a heterozygous mother. Recurrent pregnancy loss (RPL) is defined as three or more consecutive pregnancy losses. The objective was to test the gestational drive theory for the 8.1AH in women with RPL and their live born children. Methodology: We investigated the inheritance of the 8.1AH from 82 heterozygous RPL women to 110 live born children. All participants were genotyped for HLA-A, -B and -DRB1 in DNA from EDTA-treated blood or buccal swaps. Inheritance was compared with a Mendelian inheritance of 50% using a two-sided exact binomial test. Results: We found that 55% of the live born children had inherited the 8.1AH, which was not significantly higher than the expected 50% (P = 0.29). Interestingly, we found a non-significant trend toward a higher inheritance of the 8.1AH in girls, 63%, P = 0.11 as opposed to boys, 50%, P = 1.00. Conclusions and implications: We did not find that the 8.1AH was significantly more often inherited by live born children of 8.1AH heterozygous RPL women. However our data suggest that there may be a sex-specific effect which would be interesting to explore further, both in RPL and in a background population. PMID:26675299

Women's Inheritance Rights and Intergenerational Transmission of Resources in India

ERIC Educational Resources Information Center

Deininger, Klaus; Goyal, Aparajita; Nagarajan, Hari

2013-01-01

We use inheritance patterns over three generations of individuals to assess the impact of changes in the Hindu Succession Act that grant daughters equal coparcenary birth rights in joint family property that were denied to daughters in the past. We show that the amendment significantly increased daughters' likelihood to inherit land, but that…

Cytoplasmic inheritance of parent-offspring cell structure in the clonal diatom Cyclotella meneghiniana.

PubMed

Shirokawa, Yuka; Shimada, Masakazu

2016-11-16

In cytoplasmic inheritance, structural states of a parent cell could be transmitted to offspring cells via two mechanisms. The first is referred to as the hangover of parent structure, where the structure itself remains and faithfully transmits within offspring cells; the second is structural inheritance, wherein the parent structure functions as a template for development of new offspring structure. We estimated to what extent the parent structure affects the development of offspring structure by structural inheritance, using a clone of the diatom Cyclotella meneghiniana The cell has two siliceous valves (a cell wall part at both cell poles): one is inherited from the parent and the other is newly formed. We estimated cytoplasmic heritability by comparing valve traits (central fultoportulae (CTFP), striae, central area, and cell diameter) of parent and new offspring valves, using single-cell isolation and valve labelling. Parent-offspring valve trait regressions showed that all traits, except CTFP, were significantly correlated. We formulated a quantitative genetic model considering the diatom inheritance system and revealed short-term rapid evolution compared with other inheritance systems. Diatom structural inheritance will have evolved to enable clonal populations to rapidly acquire and maintain suitable structures for temporal changes in environments and life-cycle stages. © 2016 The Author(s).

Agreement Between Aging Parent’s Bequest Intention and Middle-Aged Child’s Inheritance Expectation

PubMed Central

Kim, Kyungmin

2013-01-01

Purpose: This study investigated discrepancies in expectations of aging parents and their middle-aged offspring regarding future inheritances. Methods: Data from 327 older parent–adult child dyads were analyzed. Using multilevel models, we examined factors (e.g., economic resources, family characteristics, current support exchanges, and beliefs about family obligation) associated with expectations of inheritance. We also explored patterns of correspondence in expectations over inheritance within dyads and what factors are associated with these patterns. Results: We found a significant generational difference in expectations of inheritance, with children less likely to expect inheritances than parents expected to give. Parent’s income, number of siblings, and support currently given to children were significantly associated with both parents’ and children’s positive expectations of inheritance. The effects of child’s income, support given to parent, and parent’s gender on inheritance expectations differed between parents and children. Compared with discordant dyads (parents intended to leave a bequest, but their child did not expect an inheritance), correspondent dyads (both parents and children expected a bequest) showed higher income of parents and children, more support given to the child, and lower levels of child’s filial obligation. Implications: Although bequest decisions are circumscribed by parent’s financial resources, our findings suggest that they are also a continuation of established patterns of exchanges. Parents and children form their intention or expectation about inheritance based on different factors, leaving open the possibility of misunderstandings between the generations. PMID:23197395

Some aspects of the role of rift inheritance on Alpine-type orogens

NASA Astrophysics Data System (ADS)

Tugend, Julie; Manatschal, Gianreto; Mohn, Geoffroy; Chevrot, Sébastien

2017-04-01

Processes commonly recognized as fundamental for the formation of collisional orogens include oceanic subduction, arc-continent and continent-continent collision. As collisional belts result from the closure of oceanic basins and subsequent inversion of former rifted margins, their formation and evolution may also in theory be closely interlinked with the initial architecture of the former rifted margins. This assumption is indeed more likely to be applicable in the case of Alpine-type orogens, mainly controlled by mechanical processes and mostly devoid of arc-related magmatism. More and more studies from present-day magma-poor rifted margins illustrate the complex evolution of hyperextended domains (i.e. severely thinned continental crust (<10 km) and/or exhumed serpentinized mantle with relatively minor magmatic additions) between unequivocal continental and oceanic domains. In this contribution, we compare the deep structure of the Pyrenean and Alpine belts to discuss some aspects of the relative role of rift-inherited hyperextension and collisional processes in building Alpine-type orogens. The Pyrenees and Western to Central Alps respectively result from the inversion of a Late Jurassic to Mid Cretaceous and an Early to Middle Jurassic rift system eventually floored by hyperextended crust, exhumed mantle and/or proto-oceanic crust. In spite of uncertainties on the initial width of the hyperextended and proto-oceanic domains, the rift-related pre-collisional architecture of the Alps shows many similarities with that proposed for the Pyrenees. Remnants of these domains occur in the internal parts of both orogens, but they are largely affected by orogeny-related deformation and show a HP-LT to HT-MP metamorphic overprint in the Alps as a result of a polyphase deformation history. Yet, recent high-resolution tomographic images across the Pyrenees (PYROPE) and the Alps (CIFALPS) reveal a surprisingly comparable present-day overall crustal and lithospheric structure

Widow cleansing and inheritance among the Luo in Kenya: the need for additional women-centred HIV prevention options

PubMed Central

Perry, Brian; Oluoch, Lennah; Agot, Kawango; Taylor, Jamilah; Onyango, Jacob; Ouma, Lilian; Otieno, Caroline; Wong, Christina; Corneli, Amy

2014-01-01

Introduction The customs of widow cleansing and widow inheritance are practiced in several communities throughout sub-Saharan Africa. In the Nyanza Province of Kenya, according to tradition, Luo widows are expected to engage in sexual intercourse with a “cleanser,” without the use of a condom, in order to remove the impurity ascribed to her after her husband's death. Luo couples, including widows, are also expected to engage in sex preceding specific agricultural activities, building homes, funerals, weddings, and other significant cultural and social events. Widows who are inherited for the purpose of fulfilling cultural obligation have a higher prevalence of HIV than those who remain un-inherited or are inherited for the purpose of companionship. Methods As part of a larger descriptive qualitative study to inform study procedures for FEM-PrEP, an HIV prevention pre-exposure prophylaxis clinical trial, we conducted 15 semi-structured interviews (SSIs) with widows, 15 SSIs with inheritors, and four focus group discussions with widows in the Bondo and Rarieda districts in Nyanza Province to explore the HIV risk context within widow cleansing and inheritance practices. Thematic qualitative analysis was used to analyze the data. Results The majority of widows reported in the demographic questionnaire being inherited, and most widows in the SSIs described participating in the cleansing ritual. We identified two main themes related to HIV prevention within the context of widow cleansing and inheritance: 1) widows must balance limiting their risk for HIV infection with meeting cultural expectations and ensuring that their livelihood needs are met, and 2) sexual abstinence undermines cultural expectations in widowhood while the use of condoms is deemed inappropriate in fulfilling culturally prescribed sexual rituals, and is often beyond the widow's ability to negotiate. Conclusions Women-controlled HIV prevention methods such as antiretroviral-based oral pre

Widow cleansing and inheritance among the Luo in Kenya: the need for additional women-centred HIV prevention options.

PubMed

Perry, Brian; Oluoch, Lennah; Agot, Kawango; Taylor, Jamilah; Onyango, Jacob; Ouma, Lilian; Otieno, Caroline; Wong, Christina; Corneli, Amy

2014-01-01

The customs of widow cleansing and widow inheritance are practiced in several communities throughout sub-Saharan Africa. In the Nyanza Province of Kenya, according to tradition, Luo widows are expected to engage in sexual intercourse with a "cleanser," without the use of a condom, in order to remove the impurity ascribed to her after her husband's death. Luo couples, including widows, are also expected to engage in sex preceding specific agricultural activities, building homes, funerals, weddings, and other significant cultural and social events. Widows who are inherited for the purpose of fulfilling cultural obligation have a higher prevalence of HIV than those who remain un-inherited or are inherited for the purpose of companionship. As part of a larger descriptive qualitative study to inform study procedures for FEM-PrEP, an HIV prevention pre-exposure prophylaxis clinical trial, we conducted 15 semi-structured interviews (SSIs) with widows, 15 SSIs with inheritors, and four focus group discussions with widows in the Bondo and Rarieda districts in Nyanza Province to explore the HIV risk context within widow cleansing and inheritance practices. Thematic qualitative analysis was used to analyze the data. The majority of widows reported in the demographic questionnaire being inherited, and most widows in the SSIs described participating in the cleansing ritual. We identified two main themes related to HIV prevention within the context of widow cleansing and inheritance: 1) widows must balance limiting their risk for HIV infection with meeting cultural expectations and ensuring that their livelihood needs are met, and 2) sexual abstinence undermines cultural expectations in widowhood while the use of condoms is deemed inappropriate in fulfilling culturally prescribed sexual rituals, and is often beyond the widow's ability to negotiate. Women-controlled HIV prevention methods such as antiretroviral-based oral pre-exposure prophylaxis, vaginal gels, and vaginal rings

Lay understanding of familial risk of common chronic diseases: a systematic review and synthesis of qualitative research.

PubMed

Walter, Fiona M; Emery, Jon; Braithwaite, Dejana; Marteau, Theresa M

2004-01-01

Although the family history is increasingly used for genetic risk assessment of common chronic diseases in primary care, evidence suggests that lay understanding about inheritance may conflict with medical models. This study systematically reviewed and synthesized the qualitative literature exploring understanding about familial risk held by persons with a family history of cancer, coronary artery disease, and diabetes mellitus. Twenty-two qualitative articles were found after a comprehensive literature search and were critically appraised; 11 were included. A meta-ethnographic approach was used to translate the studies across each other, synthesize the translation, and express the synthesis. A dynamic process emerged by which a personal sense of vulnerability included some features that mirror the medical factors used to assess risk, such as the number of affected relatives. Other features are more personal, such as experience of a relative's disease, sudden or premature death, perceived patterns of illness relating to gender or age at death, and comparisons between a person and an affected relative. The developing vulnerability is interpreted using personal mental models, including models of disease causation, inheritance, and fatalism. A person's sense of vulnerability affects how that person copes with, and attempts to control, any perceived familial risk. Persons with a family history of a common chronic disease develop a personal sense of vulnerability that is informed by the salience of their family history and interpreted within their personal models of disease causation and inheritance. Features that give meaning to familial risk may be perceived differently by patients and professionals. This review identifies key areas for health professionals to explore with patients that may improve the effectiveness of communication about disease risk and management.

Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs.

PubMed

Schuster, Andrew; Skinner, Michael K; Yan, Wei

Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5' halves of mature tRNAs (5' halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5' halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon.

Large-scale integrative network-based analysis identifies common pathways disrupted by copy number alterations across cancers

PubMed Central

2013-01-01

Background Many large-scale studies analyzed high-throughput genomic data to identify altered pathways essential to the development and progression of specific types of cancer. However, no previous study has been extended to provide a comprehensive analysis of pathways disrupted by copy number alterations across different human cancers. Towards this goal, we propose a network-based method to integrate copy number alteration data with human protein-protein interaction networks and pathway databases to identify pathways that are commonly disrupted in many different types of cancer. Results We applied our approach to a data set of 2,172 cancer patients across 16 different types of cancers, and discovered a set of commonly disrupted pathways, which are likely essential for tumor formation in majority of the cancers. We also identified pathways that are only disrupted in specific cancer types, providing molecular markers for different human cancers. Analysis with independent microarray gene expression datasets confirms that the commonly disrupted pathways can be used to identify patient subgroups with significantly different survival outcomes. We also provide a network view of disrupted pathways to explain how copy number alterations affect pathways that regulate cell growth, cycle, and differentiation for tumorigenesis. Conclusions In this work, we demonstrated that the network-based integrative analysis can help to identify pathways disrupted by copy number alterations across 16 types of human cancers, which are not readily identifiable by conventional overrepresentation-based and other pathway-based methods. All the results and source code are available at http://compbio.cs.umn.edu/NetPathID/. PMID:23822816

Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations.

PubMed

Arai, Yuuki; Maeda, Akiko; Hirami, Yasuhiko; Ishigami, Chie; Kosugi, Shinji; Mandai, Michiko; Kurimoto, Yasuo; Takahashi, Masayo

2015-01-01

The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD.

Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.

PubMed

McCormack, Shana E; Li, Dong; Kim, Yeon Joo; Lee, Ji Young; Kim, Soo-Hyun; Rapaport, Robert; Levine, Michael A

2017-07-01

Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. The objective of this study was to identify a genetic cause of PSIS in an affected child. Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered. Copyright © 2017 Endocrine Society

The Tasmantid Seamounts: A window into the structural inheritance of ocean floor fabric

NASA Astrophysics Data System (ADS)

Richards, F. D.; Kalnins, L. M.; Watts, A. B.; Cohen, B. E.; Beaman, R. J.

2015-12-01

The extinct Tasman Sea spreading centre, active from 84--53 Ma, is intersected at a number of locations by the Tasmantid Seamount Chain. The chain, which extends for over 2000 km off the east coast of Australia, progressively increases in age from south to north with ages ranging between 6 Ma and ˜50 Ma. While thick sediment (˜1 km) obscures much of the northern Tasman Sea basement, detailed morphological and geophysical analyses of the seamounts reveal a strong correlation between tectonic setting, seamount orientation, and volcanic structure, despite the ≥20 Ma offset between spreading cessation and initial seamount emplacement. Morphologically, structural inheritance is evidenced by the contrast between two volcanic styles: 1) the rugged, predominantly fissure-fed, fabrics characterizing seamounts emplaced at inside corners of spreading segment-transform intersections; and 2) the conical seamounts with summit craters and isolated dyke-fed flank cones that develop off-axis. Furthermore, volcanic fabrics align closely with the principal stress directions expected for a spreading ridge system in which strong mechanical coupling occurs across transform faults. This suggests that the lithosphere is dissected by numerous deep faults, allowing magma to be channelled away from the site of melting along pre-existing structural trends. The generally low effective elastic thickness, TeT_e, (≤15 km) and lack of a plate age-TeT_e relationship along the chain indicate that structural inheritance is also the major control on lithospheric strength near the extinct spreading centre. While the importance of structural inheritance in controlling magmatic behaviour is commonly acknowledged in continental settings, these results clearly demonstrate the need to also consider it in the oceanic realm.The extinct Tasman Sea spreading centre, active from 84--53 Ma, is intersected at a number of locations by the Tasmantid Seamount Chain. The chain, which extends for over 2000 km off

Plate tectonics, damage and inheritance.

PubMed

Bercovici, David; Ricard, Yanick

2014-04-24

The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates.

Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes.

PubMed

Proudhon, Charlotte; Duffié, Rachel; Ajjan, Sophie; Cowley, Michael; Iranzo, Julian; Carbajosa, Guillermo; Saadeh, Heba; Holland, Michelle L; Oakey, Rebecca J; Rakyan, Vardhman K; Schulz, Reiner; Bourc'his, Déborah

2012-09-28

Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinted gDMRs, at the Cdh15 and AK008011 loci, with tissue-specific imprinting loss, again by paternal methylation gain. Protection against demethylation after fertilization has been emphasized as instrumental in maintaining parent-of-origin methylation inherited from the gametes. Here we provide evidence that protection against de novo methylation acts as an equal major pivot, at implantation and throughout life. Copyright © 2012 Elsevier Inc. All rights reserved.

Protection against De Novo Methylation Is Instrumental in Maintaining Parent-of-Origin Methylation Inherited from the Gametes

PubMed Central

Proudhon, Charlotte; Duffié, Rachel; Ajjan, Sophie; Cowley, Michael; Iranzo, Julian; Carbajosa, Guillermo; Saadeh, Heba; Holland, Michelle L.; Oakey, Rebecca J.; Rakyan, Vardhman K.; Schulz, Reiner; Bourc’his, Déborah

2012-01-01

Summary Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinted gDMRs, at the Cdh15 and AK008011 loci, with tissue-specific imprinting loss, again by paternal methylation gain. Protection against demethylation after fertilization has been emphasized as instrumental in maintaining parent-of-origin methylation inherited from the gametes. Here we provide evidence that protection against de novo methylation acts as an equal major pivot, at implantation and throughout life. PMID:22902559

Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic transgenerational inheritance of disease and sperm epimutations.

PubMed

Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

2012-12-01

Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a "pesticide mixture" (pesticide permethrin and insect repellent N,N-diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures. Copyright © 2012 Elsevier Inc. All rights reserved.

HOW to Identify Common Nitulid Beetles Associated with Oak Wilt Mats in Minnesota

Treesearch

Steven Seybold; Jennifer Juzwik

1996-01-01

We developed this handbook for forestry professionals, land managers, and homeowners to help them identify the most common adult and larval sap beetles found in oak wilt mats in the North Central States. Although the photographs depict the natural color of adults, preserved specimens may not have exactly the same color as those in the pictures. All sizes given are...

Neo-sex chromosome inheritance across species in Silene hybrids.

PubMed

Weingartner, L A; Delph, L F

2014-07-01

Neo-sex chromosomes, which form through the major restructuring of ancestral sex chromosome systems, have evolved in various taxa. Such restructuring often consists of the fusion of an autosome to an existing sex chromosome, resulting in novel sex chromosome formations (e.g. X1X2Y or XY1Y2.). Comparative studies are often made between restructured sex chromosome systems of closely related species, and here we evaluate the consequences of variable sex chromosome systems to hybrids. If neo-sex chromosomes are improperly inherited across species, this could lead to aberrant development and reproductive isolation. In this study, we examine the fate of neo-sex chromosomes in hybrids of the flowering plants Silene diclinis and Silene latifolia. Silene diclinis has a neo-sex chromosome system (XY1Y2) that is thought to have evolved from an ancestral XY system that is still present in S. latifolia. These species do not hybridize naturally, and improper sex chromosome inheritance could contribute to reproductive isolation. We investigated whether this major restructuring of sex chromosomes prevents their proper inheritance in a variety of hybrid crosses, including some F2 - and later-generation hybrids, with sex chromosome-linked, species-specific, polymorphic markers and chromosome squashes. We discovered that despite the differences in sex chromosomes that exist between these two species, proper segregation had occurred in hybrids that made it to flowering, including later-generation hybrids, indicating that neo-sex chromosome formation alone does not result in complete reproductive isolation between these two species. Additionally, hybrids with aberrant sex expression (e.g. neuter, hermaphrodite) also inherited the restructured sex chromosomes properly, highlighting that issues with sexual development in hybrids can be caused by intrinsic genetic incompatibility rather than improper sex chromosome inheritance. © 2014 The Authors. Journal of Evolutionary Biology © 2014

The landscape of inherited and de novo copy number variants in a plasmodium falciparum genetic cross

PubMed Central

2011-01-01

Background Copy number is a major source of genome variation with important evolutionary implications. Consequently, it is essential to determine copy number variant (CNV) behavior, distributions and frequencies across genomes to understand their origins in both evolutionary and generational time frames. We use comparative genomic hybridization (CGH) microarray and the resolution provided by a segregating population of cloned progeny lines of the malaria parasite, Plasmodium falciparum, to identify and analyze the inheritance of 170 genome-wide CNVs. Results We describe CNVs in progeny clones derived from both Mendelian (i.e. inherited) and non-Mendelian mechanisms. Forty-five CNVs were present in the parent lines and segregated in the progeny population. Furthermore, extensive variation that did not conform to strict Mendelian inheritance patterns was observed. 124 CNVs were called in one or more progeny but in neither parent: we observed CNVs in more than one progeny clone that were not identified in either parent, located more frequently in the telomeric-subtelomeric regions of chromosomes and singleton de novo CNVs distributed evenly throughout the genome. Linkage analysis of CNVs revealed dynamic copy number fluctuations and suggested mechanisms that could have generated them. Five of 12 previously identified expression quantitative trait loci (eQTL) hotspots coincide with CNVs, demonstrating the potential for broad influence of CNV on the transcriptional program and phenotypic variation. Conclusions CNVs are a significant source of segregating and de novo genome variation involving hundreds of genes. Examination of progeny genome segments provides a framework to assess the extent and possible origins of CNVs. This segregating genetic system reveals the breadth, distribution and dynamics of CNVs in a surprisingly plastic parasite genome, providing a new perspective on the sources of diversity in parasite populations. PMID:21936954

Fractional populations in sex-linked inheritance

NASA Astrophysics Data System (ADS)

Pyo Lee, Seung; Chung, Myung-Hoon; Koo Kim, Chul; Nahm, Kyun

2001-03-01

We study the fractional populations in chromosome inherited diseases. The governing equations for the fractional populations are found and solved in the presence of mutation and selection. The physical fixed points obtained are used to discuss the cases of color blindness and hemophilia.

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

PubMed Central

Dunlop, Malcolm G; Dobbins, Sara E; Farrington, Susan Mary; Jones, Angela M; Palles, Claire; Whiffin, Nicola; Tenesa, Albert; Spain, Sarah; Broderick, Peter; Ooi, Li-Yin; Domingo, Enric; Smillie, Claire; Henrion, Marc; Frampton, Matthew; Martin, Lynn; Grimes, Graeme; Gorman, Maggie; Semple, Colin; Ma, Yussanne; Barclay, Ella; Prendergast, James; Cazier, Jean-Baptiste; Olver, Bianca; Carvajal-Carmona, Luis G; Ballereau, Stephane; Lloyd, Amy; Vijayakrishnan, Jayaram; Zgaga, Lina; Rudan, Igor; Theodoratou, Evropi; Starr, John M; Deary, Ian; Kirac, Iva; Kovačević, Dujo; Aaltonen, Lauri A; Renkonen-Sinisalo, Laura; Mecklin, Jukka-Pekka; Matsuda, Koichi; Nakamura, Yusuke; Okada, Yukinori; Gallinger, Steven; Duggan, David J; Conti, David; Newcomb, Polly; Hopper, John; Jenkins, Mark A.; Schumacher, Fredrick; Casey, Graham; Easton, Douglas; Shah, Mitul; Pharoah, Paul; Lindblom, Annika; Liu, Tao; Smith, Christopher G; West, Hannah; Cheadle, Jeremy P.; Midgley, Rachel; Kerr, David J; Campbell, Harry; Tomlinson, Ian P; Houlston, Richard S

2015-01-01

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totalling 21,096 cases and 19,555 controls. We identified three novel CRC risk loci at 6p21 (rs1321311, near CDKN1A; P=1.14×10−10), 11q13.4 (rs3824999, intronic to POLD3; P=3.65×10−10) and Xp22.2 (rs5934683, near SHROOM2; P=7.30×10−10) This brings to 20 the number of independent loci associated with CRC risk, and provides further insight into the genetic architecture of inherited susceptibility to CRC. PMID:22634755

Polydactyly in Development, Inheritance, and Evolution.

PubMed

Lange, Axel; Müller, Gerd B

2017-03-01

The occurrence of supernumerary digits or toes in humans and other tetrapods has attracted general interest since antiquity and later influenced scientific theories of development, inheritance, and evolution. Seventeenth-century genealogical studies of polydactyly were at the beginning of an understanding of the rules of inheritance. Features of polydactyly were also part of the classical disputes on the nature of development, including the preformation-versus-epigenesis and the atavism-versus-malformation debates. In the evolutionary domain, polydactyly was used in the criticism of the gradualist account of variation underlying Darwin’s theory. Today, extra digit formation plays a role in the conceptualization of gene regulation and pattern formation in vertebrate limb evolution. Recent genetic, experimental, and modeling accounts of extra digit formation highlight the existence of nongradual transitions in phenotypic states, suggesting a distinction between continuous and discontinuous variation in evolution. Unless otherwise noted, all translations are our own.

A second inheritance system: the extension of biology through culture.

PubMed

Whiten, Andrew

2017-10-06

By the mid-twentieth century (thus following the 'Modern Synthesis' in evolutionary biology), the behavioural sciences offered only the sketchy beginnings of a scientific literature documenting evidence for cultural inheritance in animals-the transmission of traditional behaviours via learning from others (social learning). By contrast, recent decades have seen a massive growth in the documentation of such cultural phenomena, driven by long-term field studies and complementary laboratory experiments. Here, I review the burgeoning scope of discoveries in this field, which increasingly suggest that this 'second inheritance system', built on the shoulders of the primary genetic inheritance system, occurs widely among vertebrates and possibly in invertebrates too. Its novel characteristics suggest significant implications for our understanding of evolutionary biology. I assess the extent to which this second system extends the scope of evolution, both by echoing principal properties of the primary, organic evolutionary system, and going beyond it in significant ways. This is well established in human cultural evolution; here, I address animal cultures more generally. The further major, and related, question concerns the extent to which the consequences of widespread animal cultural transmission interact with the primary, genetically based inheritance systems, shaping organic evolution.

Inherited Chromosomally Integrated Human Herpesvirus 6 Genomes Are Ancient, Intact, and Potentially Able To Reactivate from Telomeres

PubMed Central

Zhang, Enjie; Bell, Adam J.; Wilkie, Gavin S.; Suárez, Nicolás M.; Batini, Chiara; Veal, Colin D.; Armendáriz-Castillo, Isaac; Neumann, Rita; Cotton, Victoria E.; Huang, Yan; Porteous, David J.; Jarrett, Ruth F.; Davison, Andrew J.

2017-01-01

ABSTRACT The genomes of human herpesvirus 6A (HHV-6A) and HHV-6B have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere, and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes. Here, we report an analysis of 28 ciHHV-6 genomes and show that they are significantly divergent from the few modern nonintegrated HHV-6 strains for which complete sequences are currently available. In addition, ciHHV-6B genomes in Europeans are more closely related to each other than to ciHHV-6B genomes from China and Pakistan, suggesting regional variation of the trait. Remarkably, at least one group of European ciHHV-6B carriers has inherited the same ciHHV-6B genome, integrated in the same telomere allele, from a common ancestor estimated to have existed 24,500 ± 10,600 years ago. Despite the antiquity of some, and possibly most, germ line HHV-6 integrations, the majority of ciHHV-6B (95%) and ciHHV-6A (72%) genomes contain a full set of intact viral genes and therefore appear to have the capacity for viral gene expression and full reactivation. IMPORTANCE Inheritance of HHV-6A or HHV-6B integrated into a telomere occurs at a low frequency in most populations studied to date, but its characteristics are poorly understood. However, stratification of ciHHV-6 carriers in modern populations due to common ancestry is an important consideration for genome-wide association studies that aim to identify disease risks for these people. Here, we present full sequence analysis of 28 ciHHV-6 genomes and show that ciHHV-6B in many carriers with European ancestry most likely originated from ancient integration events in a small number of

Inherited Chromosomally Integrated Human Herpesvirus 6 Genomes Are Ancient, Intact, and Potentially Able To Reactivate from Telomeres.

PubMed

Zhang, Enjie; Bell, Adam J; Wilkie, Gavin S; Suárez, Nicolás M; Batini, Chiara; Veal, Colin D; Armendáriz-Castillo, Isaac; Neumann, Rita; Cotton, Victoria E; Huang, Yan; Porteous, David J; Jarrett, Ruth F; Davison, Andrew J; Royle, Nicola J

2017-11-15

The genomes of human herpesvirus 6A (HHV-6A) and HHV-6B have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere, and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes. Here, we report an analysis of 28 ciHHV-6 genomes and show that they are significantly divergent from the few modern nonintegrated HHV-6 strains for which complete sequences are currently available. In addition, ciHHV-6B genomes in Europeans are more closely related to each other than to ciHHV-6B genomes from China and Pakistan, suggesting regional variation of the trait. Remarkably, at least one group of European ciHHV-6B carriers has inherited the same ciHHV-6B genome, integrated in the same telomere allele, from a common ancestor estimated to have existed 24,500 ± 10,600 years ago. Despite the antiquity of some, and possibly most, germ line HHV-6 integrations, the majority of ciHHV-6B (95%) and ciHHV-6A (72%) genomes contain a full set of intact viral genes and therefore appear to have the capacity for viral gene expression and full reactivation. IMPORTANCE Inheritance of HHV-6A or HHV-6B integrated into a telomere occurs at a low frequency in most populations studied to date, but its characteristics are poorly understood. However, stratification of ciHHV-6 carriers in modern populations due to common ancestry is an important consideration for genome-wide association studies that aim to identify disease risks for these people. Here, we present full sequence analysis of 28 ciHHV-6 genomes and show that ciHHV-6B in many carriers with European ancestry most likely originated from ancient integration events in a small number of ancestors

Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

PubMed Central

Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

2015-01-01

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307–316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod–cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone–rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. PMID:25324231

17 CFR 240.16b-5 - Bona fide gifts and inheritance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bona fide gifts and inheritance. 240.16b-5 Section 240.16b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... gifts and inheritance. Both the acquisition and the disposition of equity securities shall be exempt...

MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance.

PubMed

Lev, Itamar; Seroussi, Uri; Gingold, Hila; Bril, Roberta; Anava, Sarit; Rechavi, Oded

2017-04-24

In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs. We discovered that MET-2 inhibits small RNA inheritance, and, as a consequence, induction of RNAi in met-2 mutants leads to permanent RNAi responses that do not terminate even after more than 30 generations. We found that potentiation of heritable RNAi in met-2 animals results from global hyperactivation of the small RNA inheritance machinery. Thus, changes in histone modifications can give rise to drastic transgenerational epigenetic effects, by controlling the overall potency of small RNA inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel inherited mutation of the transcription factor RUNX1 causes thrombocytopenia and may predispose to acute myeloid leukaemia.

PubMed

Walker, Logan C; Stevens, Jane; Campbell, Hamish; Corbett, Rob; Spearing, Ruth; Heaton, David; Macdonald, Donald H; Morris, Christine M; Ganly, Peter

2002-06-01

The RUNX1 (AML1, CBFA2) gene is a member of the runt transcription factor family, responsible for DNA binding and heterodimerization of other non-DNA binding transcription factors. RUNX1 plays an important part in regulating haematopoiesis and it is frequently disrupted by illegitimate somatic recombination in both acute myeloid and lymphoblastic leukaemia. Germline mutations of RUNX1 have also recently been described and are dominantly associated with inherited leukaemic conditions. We have identified a unique point mutation of the RUNX1 gene (A107P) in members of a family with autosomal dominant inheritance of thrombocytopenia. One member has developed acute myeloid leukaemia (AML).

Network-based analysis of genotype-phenotype correlations between different inheritance modes.

PubMed

Hao, Dapeng; Li, Chuanxing; Zhang, Shaojun; Lu, Jianping; Jiang, Yongshuai; Wang, Shiyuan; Zhou, Meng

2014-11-15

Recent studies on human disease have revealed that aberrant interaction between proteins probably underlies a substantial number of human genetic diseases. This suggests a need to investigate disease inheritance mode using interaction, and based on which to refresh our conceptual understanding of a series of properties regarding inheritance mode of human disease. We observed a strong correlation between the number of protein interactions and the likelihood of a gene causing any dominant diseases or multiple dominant diseases, whereas no correlation was observed between protein interaction and the likelihood of a gene causing recessive diseases. We found that dominant diseases are more likely to be associated with disruption of important interactions. These suggest inheritance mode should be understood using protein interaction. We therefore reviewed the previous studies and refined an interaction model of inheritance mode, and then confirmed that this model is largely reasonable using new evidences. With these findings, we found that the inheritance mode of human genetic diseases can be predicted using protein interaction. By integrating the systems biology perspectives with the classical disease genetics paradigm, our study provides some new insights into genotype-phenotype correlations. haodapeng@ems.hrbmu.edu.cn or biofomeng@hotmail.com Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Orogenic structural inheritance and rifted passive margin formation

NASA Astrophysics Data System (ADS)

Salazar Mora, Claudio A.; Huismans, Ritske S.

2016-04-01

Structural inheritance is related to mechanical weaknesses in the lithosphere due to previous tectonic events, e.g. rifting, subduction and collision. The North and South Atlantic rifted passive margins that formed during the breakup of Western Gondwana, are parallel to the older Caledonide and the Brasiliano-Pan-African orogenic belts. In the South Atlantic, 'old' mantle lithospheric fabric resulting from crystallographic preferred orientation of olivine is suggested to play a role during rifted margin formation (Tommasi and Vauchez, 2001). Magnetometric and gravimetric mapping of onshore structures in the Camamu and Almada basins suggest that extensional faults are controlled by two different directions of inherited older Brasiliano structures in the upper lithosphere (Ferreira et al., 2009). In the South Atlantic Campos Basin, 3D seismic data indicate that inherited basement structures provide a first order control on basin structure (Fetter, 2009). Here we investigate the role of structural inheritance on the formation of rifted passive margins with high-resolution 2D thermo-mechanical numerical experiments. The numerical domain is 1200 km long and 600 km deep and represents the lithosphere and the sublithospheric mantle. Model experiments were carried out by creating self-consistent orogenic inheritance where a first phase of orogen formation is followed by extension. We focus in particular on the role of varying amount of orogenic shortening, crustal rheology, contrasting styles of orogen formation on rifted margin style, and the time delay between orogeny and subsequent rifted passive formation. Model results are compared to contrasting structural styles of rifted passive margin formation as observed in the South Atlantic. Ferreira, T.S., Caixeta, J.M., Lima, F.D., 2009. Basement control in Camamu and Almada rift basins. Boletim de Geociências da Petrobrás 17, 69-88. Fetter, M., 2009. The role of basement tectonic reactivation on the structural evolution

Mitochondrial anchorage and fusion contribute to mitochondrial inheritance and quality control in the budding yeast Saccharomyces cerevisiae.

PubMed

Higuchi-Sanabria, Ryo; Charalel, Joseph K; Viana, Matheus P; Garcia, Enrique J; Sing, Cierra N; Koenigsberg, Andrea; Swayne, Theresa C; Vevea, Jason D; Boldogh, Istvan R; Rafelski, Susanne M; Pon, Liza A

2016-03-01

Higher-functioning mitochondria that are more reduced and have less ROS are anchored in the yeast bud tip by the Dsl1-family protein Mmr1p. Here we report a role for mitochondrial fusion in bud-tip anchorage of mitochondria. Fluorescence loss in photobleaching (FLIP) and network analysis experiments revealed that mitochondria in large buds are a continuous reticulum that is physically distinct from mitochondria in mother cells. FLIP studies also showed that mitochondria that enter the bud can fuse with mitochondria that are anchored in the bud tip. In addition, loss of fusion and mitochondrial DNA (mtDNA) by deletion of mitochondrial outer or inner membrane fusion proteins (Fzo1p or Mgm1p) leads to decreased accumulation of mitochondria at the bud tip and inheritance of fitter mitochondria by buds compared with cells with no mtDNA. Conversely, increasing the accumulation and anchorage of mitochondria in the bud tip by overexpression of MMR1 results in inheritance of less-fit mitochondria by buds and decreased replicative lifespan and healthspan. Thus quantity and quality of mitochondrial inheritance are ensured by two opposing processes: bud-tip anchorage by mitochondrial fusion and Mmr1p, which favors bulk inheritance; and quality control mechanisms that promote segregation of fitter mitochondria to the bud. © 2016 Higuchi-Sanabria et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Analysis of Rules for Islamic Inheritance Law in Indonesia Using Hybrid Rule Based Learning

NASA Astrophysics Data System (ADS)

Khosyi'ah, S.; Irfan, M.; Maylawati, D. S.; Mukhlas, O. S.

2018-01-01

Along with the development of human civilization in Indonesia, the changes and reform of Islamic inheritance law so as to conform to the conditions and culture cannot be denied. The distribution of inheritance in Indonesia can be done automatically by storing the rule of Islamic inheritance law in the expert system. In this study, we analyze the knowledge of experts in Islamic inheritance in Indonesia and represent it in the form of rules using rule-based Forward Chaining (FC) and Davis-Putman-Logemann-Loveland (DPLL) algorithms. By hybridizing FC and DPLL algorithms, the rules of Islamic inheritance law in Indonesia are clearly defined and measured. The rules were conceptually validated by some experts in Islamic laws and informatics. The results revealed that generally all rules were ready for use in an expert system.

Inheritable and sporadic non-autoimmune hyperthyroidism.

PubMed

Ferraz, Carolina; Paschke, Ralf

2017-03-01

Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Meta-QTL for resistance to white mold in common bean

PubMed Central

Vasconcellos, Renato C. C.; Oraguzie, O. Blessing; Soler, Alvaro; Arkwazee, Haidar; Myers, James R.; Ferreira, Juan J.; Song, Qijian; McClean, Phil; Miklas, Phillip N.

2017-01-01

White mold, caused by the fungus Sclerotinia sclerotiorum (Lib.) de Bary, is a major disease that limits common bean production and quality worldwide. The host-pathogen interaction is complex, with partial resistance in the host inherited as a quantitative trait with low to moderate heritability. Our objective was to identify meta-QTL conditioning partial resistance to white mold from individual QTL identified across multiple populations and environments. The physical positions for 37 individual QTL were identified across 14 recombinant inbred bi-parental populations (six new, three re-genotyped, and five from the literature). A meta-QTL analysis of the 37 QTL was conducted using the genetic linkage map of Stampede x Red Hawk population as the reference. The 37 QTL condensed into 17 named loci (12 previously named and five new) of which nine were defined as meta-QTL WM1.1, WM2.2, WM3.1, WM5.4, WM6.2, WM7.1, WM7.4, WM7.5, and WM8.3. The nine meta-QTL had confidence intervals ranging from 0.65 to 9.41 Mb. Candidate genes shown to express under S. sclerotiorum infection in other studies, including cell wall receptor kinase, COI1, ethylene responsive transcription factor, peroxidase, and MYB transcription factor, were found within the confidence interval for five of the meta-QTL. The nine meta-QTL are recommended as potential targets for MAS for partial resistance to white mold in common bean. PMID:28199342

Familial temporal lobe epilepsy autosomal dominant inheritance in a large pedigree from southern Italy.

PubMed

Gambardella, A; Messina, D; Le Piane, E; Oliveri, R L; Annesi, G; Zappia, M; Andermann, E; Quattrone, A; Aguglia, U

2000-02-01

To further elucidate the inheritance pattern and range of phenotypic manifestations of benign familial temporal lobe epilepsy (FTLE), we report a large family recently identified in southern Italy. There were 8 patients (4 men), ranging in age from 31 to 68 years in three generations. One affected patient was deceased at the time of the study. Genealogical study strongly supported autosomal dominant inheritance with incomplete penetrance, as three unaffected individuals transmitted the disease. Clinical anticipation could not be assessed because of the ascertainment method. Male to male transmission occurred. Identifiable antecedents for seizures were present in only two patients, who had a simple febrile convulsion and a closed head trauma, respectively. Migraine was overrepresented in this family. Onset of seizures ranged from 17 to 52 years (mean: 27 years). All patients had weekly simple partial seizures suggestive of temporal origin with vegetative or experiential phenomena. Very rare partial complex seizures occurred in 6/7 patients. One had two generalized nocturnal seizures as well. Two had previously been misdiagnosed as having gastritis or panic attacks, and one had not been diagnosed. Interictal anteromesiotemporal spiking was seen in 5/7 patients, and occurred mostly during NREM sleep. Neurological examination, brain CT or MR scans were normal. Antiepileptic medication always controlled the seizures.

Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Susceptibility

PubMed Central

Nilsson, Eric E.; Skinner, Michael K.

2014-01-01

Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed in regards to disease etiology. PMID:24657180

Genome-Wide Association Study Identifies NBS-LRR-Encoding Genes Related with Anthracnose and Common Bacterial Blight in the Common Bean.

PubMed

Wu, Jing; Zhu, Jifeng; Wang, Lanfen; Wang, Shumin

2017-01-01

Nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes represent the largest and most important disease resistance genes in plants. The genome sequence of the common bean ( Phaseolus vulgaris L.) provides valuable data for determining the genomic organization of NBS-LRR genes. However, data on the NBS-LRR genes in the common bean are limited. In total, 178 NBS-LRR-type genes and 145 partial genes (with or without a NBS) located on 11 common bean chromosomes were identified from genome sequences database. Furthermore, 30 NBS-LRR genes were classified into Toll/interleukin-1 receptor (TIR)-NBS-LRR (TNL) types, and 148 NBS-LRR genes were classified into coiled-coil (CC)-NBS-LRR (CNL) types. Moreover, the phylogenetic tree supported the division of these PvNBS genes into two obvious groups, TNL types and CNL types. We also built expression profiles of NBS genes in response to anthracnose and common bacterial blight using qRT-PCR. Finally, we detected nine disease resistance loci for anthracnose (ANT) and seven for common bacterial blight (CBB) using the developed NBS-SSR markers. Among these loci, NSSR24, NSSR73, and NSSR265 may be located at new regions for ANT resistance, while NSSR65 and NSSR260 may be located at new regions for CBB resistance. Furthermore, we validated NSSR24, NSSR65, NSSR73, NSSR260, and NSSR265 using a new natural population. Our results provide useful information regarding the function of the NBS-LRR proteins and will accelerate the functional genomics and evolutionary studies of NBS-LRR genes in food legumes. NBS-SSR markers represent a wide-reaching resource for molecular breeding in the common bean and other food legumes. Collectively, our results should be of broad interest to bean scientists and breeders.

Genome-Wide Association Study Identifies NBS-LRR-Encoding Genes Related with Anthracnose and Common Bacterial Blight in the Common Bean

PubMed Central

Wu, Jing; Zhu, Jifeng; Wang, Lanfen; Wang, Shumin

2017-01-01

Nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes represent the largest and most important disease resistance genes in plants. The genome sequence of the common bean (Phaseolus vulgaris L.) provides valuable data for determining the genomic organization of NBS-LRR genes. However, data on the NBS-LRR genes in the common bean are limited. In total, 178 NBS-LRR-type genes and 145 partial genes (with or without a NBS) located on 11 common bean chromosomes were identified from genome sequences database. Furthermore, 30 NBS-LRR genes were classified into Toll/interleukin-1 receptor (TIR)-NBS-LRR (TNL) types, and 148 NBS-LRR genes were classified into coiled-coil (CC)-NBS-LRR (CNL) types. Moreover, the phylogenetic tree supported the division of these PvNBS genes into two obvious groups, TNL types and CNL types. We also built expression profiles of NBS genes in response to anthracnose and common bacterial blight using qRT-PCR. Finally, we detected nine disease resistance loci for anthracnose (ANT) and seven for common bacterial blight (CBB) using the developed NBS-SSR markers. Among these loci, NSSR24, NSSR73, and NSSR265 may be located at new regions for ANT resistance, while NSSR65 and NSSR260 may be located at new regions for CBB resistance. Furthermore, we validated NSSR24, NSSR65, NSSR73, NSSR260, and NSSR265 using a new natural population. Our results provide useful information regarding the function of the NBS-LRR proteins and will accelerate the functional genomics and evolutionary studies of NBS-LRR genes in food legumes. NBS-SSR markers represent a wide-reaching resource for molecular breeding in the common bean and other food legumes. Collectively, our results should be of broad interest to bean scientists and breeders. PMID:28848595

Co-Inheritance Analysis within the Domains of Life Substantially Improves Network Inference by Phylogenetic Profiling

PubMed Central

Shin, Junha; Lee, Insuk

2015-01-01

Phylogenetic profiling, a network inference method based on gene inheritance profiles, has been widely used to construct functional gene networks in microbes. However, its utility for network inference in higher eukaryotes has been limited. An improved algorithm with an in-depth understanding of pathway evolution may overcome this limitation. In this study, we investigated the effects of taxonomic structures on co-inheritance analysis using 2,144 reference species in four query species: Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens. We observed three clusters of reference species based on a principal component analysis of the phylogenetic profiles, which correspond to the three domains of life—Archaea, Bacteria, and Eukaryota—suggesting that pathways inherit primarily within specific domains or lower-ranked taxonomic groups during speciation. Hence, the co-inheritance pattern within a taxonomic group may be eroded by confounding inheritance patterns from irrelevant taxonomic groups. We demonstrated that co-inheritance analysis within domains substantially improved network inference not only in microbe species but also in the higher eukaryotes, including humans. Although we observed two sub-domain clusters of reference species within Eukaryota, co-inheritance analysis within these sub-domain taxonomic groups only marginally improved network inference. Therefore, we conclude that co-inheritance analysis within domains is the optimal approach to network inference with the given reference species. The construction of a series of human gene networks with increasing sample sizes of the reference species for each domain revealed that the size of the high-accuracy networks increased as additional reference species genomes were included, suggesting that within-domain co-inheritance analysis will continue to expand human gene networks as genomes of additional species are sequenced. Taken together, we propose that co-inheritance

Muscular MRI-based algorithm to differentiate inherited myopathies presenting with spinal rigidity.

PubMed

Tordjman, Mickael; Dabaj, Ivana; Laforet, Pascal; Felter, Adrien; Ferreiro, Ana; Biyoukar, Moustafa; Law-Ye, Bruno; Zanoteli, Edmar; Castiglioni, Claudia; Rendu, John; Beroud, Christophe; Chamouni, Alexandre; Richard, Pascale; Mompoint, Dominique; Quijano-Roy, Susana; Carlier, Robert-Yves

2018-05-25

Inherited myopathies are major causes of muscle atrophy and are often characterized by rigid spine syndrome, a clinical feature designating patients with early spinal contractures. We aim to present a decision algorithm based on muscular whole body magnetic resonance imaging (mWB-MRI) as a unique tool to orientate the diagnosis of each inherited myopathy long before the genetically confirmed diagnosis. This multicentre retrospective study enrolled 79 patients from referral centres in France, Brazil and Chile. The patients underwent 1.5-T or 3-T mWB-MRI. The protocol comprised STIR and T1 sequences in axial and coronal planes, from head to toe. All images were analyzed manually by multiple raters. Fatty muscle replacement was evaluated on mWB-MRI using both the Mercuri scale and statistical comparison based on the percentage of affected muscle. Between February 2005 and December 2015, 76 patients with genetically confirmed inherited myopathy were included. They were affected by Pompe disease or harbored mutations in RYR1, Collagen VI, LMNA, SEPN1, LAMA2 and MYH7 genes. Each myopathy had a specific pattern of affected muscles recognizable on mWB-MRI. This allowed us to create a novel decision algorithm for patients with rigid spine syndrome by segregating these signs. This algorithm was validated by five external evaluators on a cohort of seven patients with a diagnostic accuracy of 94.3% compared with the genetic diagnosis. We provide a novel decision algorithm based on muscle fat replacement graded on mWB-MRI that allows diagnosis and differentiation of inherited myopathies presenting with spinal rigidity. • Inherited myopathies are rare, diagnosis is challenging and genetic tests require specialized centres and often take years. • Inherited myopathies are often characterized by spinal rigidity. • Whole body magnetic resonance imaging is a unique tool to orientate the diagnosis of each inherited myopathy presenting with spinal rigidity. • Each inherited

Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs

PubMed Central

Schuster, Andrew; Skinner, Michael K.; Yan, Wei

2016-01-01

Abstract Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5′ halves of mature tRNAs (5′ halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5′ halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon. PMID:27390623

Matrilineal inheritance of a key mediator of prenatal maternal effects

PubMed Central

Ziegler, Ann-Kathrin; Pick, Joel L.; Okuliarová, Monika; Zeman, Michal

2016-01-01

Sex-linkage is predicted to evolve in response to sex-specific or sexually antagonistic selection. In line with this prediction, most sex-linked genes are associated with reproduction in the respective sex. In addition to traits directly involved in fertility and fecundity, mediators of maternal effects may be predisposed to evolve sex-linkage, because they indirectly affect female fitness through their effect on offspring phenotype. Here, we test for sex-linked inheritance of a key mediator of prenatal maternal effects in oviparous species, the transfer of maternally derived testosterone to the eggs. Consistent with maternal inheritance, we found that in Japanese quail (Coturnix japonica) granddaughters resemble their maternal (but not their paternal) grandmother in yolk testosterone deposition. This pattern of resemblance was not due to non-genetic priming effects of testosterone exposure during prenatal development, as an experimental manipulation of yolk testosterone levels did not affect the females' testosterone transfer to their own eggs later in life. Instead, W chromosome and/or mitochondrial variation may underlie the observed matrilineal inheritance pattern. Ultimately, the inheritance of mediators of maternal effects along the maternal line will allow for a fast and direct response to female-specific selection, thereby affecting the dynamics of evolutionary processes mediated by maternal effects. PMID:27629040

[Discussion on inheritance,innovation and belongingness of acupuncture-moxibustion research].

PubMed

Cai, Ronglin; Hu, Ling

2016-08-12

Three points on the inheritance,innovation and belongingness of acupuncture-moxibustion research are discussed in the paper,including the inheritance of acupuncture-moxibustion culture showing the soul of the development of acupuncture,the improvement of acupuncture-moxibustion presenting the close relationship with the innovation and its development belonging to the origin. It is considered that the inheritance of acupuncture-moxibustion culture takes the priority of its development. Innovation must be realized in order to exist better in the future medicine. The study of acupuncture-moxibustion can not be limited to the traditional acupuncture-moxibustion theory,but need to be in line with it. Explore actively the value of traditional acupuncture-moxibustion culture and its theory. The research and education of acupuncture-moxibustion must belong to TCM. With all the above condition,the innovation and development of acupuncture-moxibustion could be better achieved.

Formative Assessment: Using Concept Cartoon, Pupils' Drawings, and Group Discussions to Tackle Children's Ideas about Biological Inheritance

ERIC Educational Resources Information Center

Chin, Christine; Teou, Lay-Yen

2010-01-01

This study was carried out in the context of formative assessment where assessment and learning were integrated to enhance both teaching and learning. The purpose of the study was to: (a) identify pupils' ideas about biological inheritance through the use of a concept cartoon, pupils' drawings and talk, and (b) devise scaffolding structures that…

VIPER: a visualisation tool for exploring inheritance inconsistencies in genotyped pedigrees

PubMed Central

2012-01-01

Background Pedigree genotype datasets are used for analysing genetic inheritance and to map genetic markers and traits. Such datasets consist of hundreds of related animals genotyped for thousands of genetic markers and invariably contain multiple errors in both the pedigree structure and in the associated individual genotype data. These errors manifest as apparent inheritance inconsistencies in the pedigree, and invalidate analyses of marker inheritance patterns across the dataset. Cleaning raw datasets of bad data points (incorrect pedigree relationships, unreliable marker assays, suspect samples, bad genotype results etc.) requires expert exploration of the patterns of exposed inconsistencies in the context of the inheritance pedigree. In order to assist this process we are developing VIPER (Visual Pedigree Explorer), a software tool that integrates an inheritance-checking algorithm with a novel space-efficient pedigree visualisation, so that reported inheritance inconsistencies are overlaid on an interactive, navigable representation of the pedigree structure. Methods and results This paper describes an evaluation of how VIPER displays the different scales and types of dataset that occur experimentally, with a description of how VIPER's display interface and functionality meet the challenges presented by such data. We examine a range of possible error types found in real and simulated pedigree genotype datasets, demonstrating how these errors are exposed and explored using the VIPER interface and we evaluate the utility and usability of the interface to the domain expert. Evaluation was performed as a two stage process with the assistance of domain experts (geneticists). The initial evaluation drove the iterative implementation of further features in the software prototype, as required by the users, prior to a final functional evaluation of the pedigree display for exploring the various error types, data scales and structures. Conclusions The VIPER display was

School Grounds Guide: A Pictured Guide for Identifying Common Organisms Found In and Around the School Ground.

ERIC Educational Resources Information Center

Bain, Rodney

Designed for quick, easy identification of some of the most commonly encountered organisms found in and around the school ground, this illustrated guide identifies by a picture and a short biological description the common animals and plants found in and around school lawns, house lawns, parks, fence rows, flower gardens, vacant lots, and…

Overexpression of Human-Derived DNMT3A Induced Intergenerational Inheritance of Active DNA Methylation Changes in Rat Sperm

PubMed Central

Zheng, Xiaoguo; Li, Zhenhua; Wang, Guishuan; Li, Zhengzheng; Liang, Ajuan; Wang, Hanshu; Dai, Yubing; Huang, Xingxu; Chen, Xuejin; Ma, Yuanwu; Sun, Fei

2017-01-01

DNA methylation is the major focus of studies on paternal epigenetic inheritance in mammals, but most previous studies about inheritable DNA methylation changes are passively induced by environmental factors. However, it is unclear whether the active changes mediated by variations in DNA methyltransferase activity are heritable. Here, we established human-derived DNMT3A (hDNMT3A) transgenic rats to study the effect of hDNMT3A overexpression on the DNA methylation pattern of rat sperm and to investigate whether this actively altered DNA methylation status is inheritable. Our results revealed that hDNMT3A was overexpressed in the testis of transgenic rats and induced genome-wide alterations in the DNA methylation pattern of rat sperm. Among 5438 reliable loci identified with 64 primer-pair combinations using a methylation-sensitive amplification polymorphism method, 28.01% showed altered amplified band types. Among these amplicons altered loci, 68.42% showed an altered DNA methylation status in the offspring of transgenic rats compared with wild-type rats. Further analysis based on loci which had identical DNA methylation status in all three biological replicates revealed that overexpression of hDNMT3A in paternal testis induced hypermethylation in sperm of both genotype-negative and genotype-positive offspring. Among the differentially methylated loci, 34.26% occurred in both positive and negative offspring of transgenic rats, indicating intergenerational inheritance of active DNA methylation changes in the absence of hDNM3A transmission. Furthermore, 75.07% of the inheritable loci were hyper-methylated while the remaining were hypomethylated. Distribution analysis revealed that the DNA methylation variations mainly occurred in introns and intergenic regions. Functional analysis revealed that genes related to differentially methylated loci were involved in a wide range of functions. Finally, this study demonstrated that active DNA methylation changes induced by h

Variant pathogenicity evaluation in the community-driven Inherited Neuropathy Variant Browser.

PubMed

Saghira, Cima; Bis, Dana M; Stanek, David; Strickland, Alleene; Herrmann, David N; Reilly, Mary M; Scherer, Steven S; Shy, Michael E; Züchner, Stephan

2018-05-01

Charcot-Marie-Tooth disease (CMT) is an umbrella term for inherited neuropathies affecting an estimated one in 2,500 people. Over 120 CMT and related genes have been identified and clinical gene panels often contain more than 100 genes. Such a large genomic space will invariantly yield variants of uncertain clinical significance (VUS) in nearly any person tested. This rise in number of VUS creates major challenges for genetic counseling. Additionally, fewer individual variants in known genes are being published as the academic merit is decreasing, and most testing now happens in clinical laboratories, which typically do not correlate their variants with clinical phenotypes. For CMT, we aim to encourage and facilitate the global capture of variant data to gain a large collection of alleles in CMT genes, ideally in conjunction with phenotypic information. The Inherited Neuropathy Variant Browser provides user-friendly open access to currently reported variation in CMT genes. Geneticists, physicians, and genetic counselors can enter variants detected by clinical tests or in research studies in addition to genetic variation gathered from published literature, which are then submitted to ClinVar biannually. Active participation of the broader CMT community will provide an advance over existing resources for interpretation of CMT genetic variation. © 2018 Wiley Periodicals, Inc.

RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction.

PubMed

Voermans, N C; Snoeck, M; Jungbluth, H

2016-10-01

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide spectrum of inherited myopathies presenting throughout life. Malignant hyperthermia susceptibility (MHS)-related RYR1 mutations have emerged as a common cause of exertional rhabdomyolysis, accounting for up to 30% of rhabdomyolysis episodes in otherwise healthy individuals. Common triggers are exercise and heat and, less frequently, viral infections, alcohol and drugs. Most subjects are normally strong and have no personal or family history of malignant hyperthermia. Heat intolerance and cold-induced muscle stiffness may be a feature. Recognition of this (probably not uncommon) rhabdomyolysis cause is vital for effective counselling, to identify potentially malignant hyperthermia-susceptible individuals and to adapt training regimes. Studies in various animal models provide insights regarding possible pathophysiological mechanisms and offer therapeutic perspectives. Copyright © 2016. Published by Elsevier Masson SAS.

Multifactorial inheritance with cultural transmission and assortative mating. II. a general model of combined polygenic and cultural inheritance.

PubMed Central

Cloninger, C R; Rice, J; Reich, T

1979-01-01

A general linear model of combined polygenic-cultural inheritance is described. The model allows for phenotypic assortative mating, common environment, maternal and paternal effects, and genic-cultural correlation. General formulae for phenotypic correlation between family members in extended pedigrees are given for both primary and secondary assortative mating. A FORTRAN program BETA, available upon request, is used to provide maximum likelihood estimates of the parameters from reported correlations. American data about IQ and Burks' culture index are analyzed. Both cultural and genetic components of phenotypic variance are observed to make significant and substantial contributions to familial resemblance in IQ. The correlation between the environments of DZ twins is found to equal that of singleton sibs, not that of MZ twins. Burks' culture index is found to be an imperfect measure of midparent IQ rather than an index of home environment as previously assumed. Conditions under which the parameters of the model may be uniquely and precisely estimated are discussed. Interpretation of variance components in the presence of assortative mating and genic-cultural covariance is reviewed. A conservative, but robust, approach to the use of environmental indices is described. PMID:453202

COLD-PCR and microarray: two independent highly sensitive approaches allowing the identification of fetal paternally inherited mutations in maternal plasma.

PubMed

Galbiati, Silvia; Monguzzi, Alessandra; Damin, Francesco; Soriani, Nadia; Passiu, Marianna; Castellani, Carlo; Natacci, Federica; Curcio, Cristina; Seia, Manuela; Lalatta, Faustina; Chiari, Marcella; Ferrari, Maurizio; Cremonesi, Laura

2016-07-01

Until now, non-invasive prenatal diagnosis of genetic diseases found only limited routine applications. In autosomal recessive diseases, it can be used to determine the carrier status of the fetus through the detection of a paternally inherited disease allele in cases where maternal and paternal mutated alleles differ. Conditions for non-invasive identification of fetal paternally inherited mutations in maternal plasma were developed by two independent approaches: coamplification at lower denaturation temperature-PCR (COLD-PCR) and highly sensitive microarrays. Assays were designed for identifying 14 mutations, 7 causing β-thalassaemia and 7 cystic fibrosis. In total, 87 non-invasive prenatal diagnoses were performed by COLD-PCR in 75 couples at risk for β-thalassaemia and 12 for cystic fibrosis. First, to identify the more appropriate methodology for the analysis of minority mutated fetal alleles in maternal plasma, both fast and full COLD-PCR protocols were developed for the most common Italian β-thalassaemia Cd39 and IVSI.110 mutations. In 5 out of 31 samples, no enrichment was obtained with the fast protocol, while full COLD-PCR provided the correct fetal genotypes. Thus, full COLD-PCR protocols were developed for all the remaining mutations and all analyses confirmed the fetal genotypes obtained by invasive prenatal diagnosis. Microarray analysis was performed on 40 samples from 28 couples at risk for β-thalassaemia and 12 for cystic fibrosis. Results were in complete concordance with those obtained by both COLD-PCR and invasive procedures. COLD-PCR and microarray approaches are not expensive, simple to handle, fast and can be easily set up in specialised clinical laboratories where prenatal diagnosis is routinely performed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Early behavioural changes in familial Alzheimer's disease in the Dominantly Inherited Alzheimer Network.

PubMed

Ringman, John M; Liang, Li-Jung; Zhou, Yan; Vangala, Sitaram; Teng, Edmond; Kremen, Sarah; Wharton, David; Goate, Alison; Marcus, Daniel S; Farlow, Martin; Ghetti, Bernardino; McDade, Eric; Masters, Colin L; Mayeux, Richard P; Rossor, Martin; Salloway, Stephen; Schofield, Peter R; Cummings, Jeffrey L; Buckles, Virginia; Bateman, Randall; Morris, John C

2015-04-01

Prior studies indicate psychiatric symptoms such as depression, apathy and anxiety are risk factors for or prodromal symptoms of incipient Alzheimer's disease. The study of persons at 50% risk for inheriting autosomal dominant Alzheimer's disease mutations allows characterization of these symptoms before progressive decline in a population destined to develop illness. We sought to characterize early behavioural features in carriers of autosomal dominant Alzheimer's disease mutations. Two hundred and sixty-one persons unaware of their mutation status enrolled in the Dominantly Inherited Alzheimer Network, a study of persons with or at-risk for autosomal dominant Alzheimer's disease, were evaluated with the Neuropsychiatric Inventory-Questionnaire, the 15-item Geriatric Depression Scale and the Clinical Dementia Rating Scale (CDR). Ninety-seven asymptomatic (CDR = 0), 25 mildly symptomatic (CDR = 0.5), and 33 overtly affected (CDR > 0.5) autosomal dominant Alzheimer's disease mutation carriers were compared to 106 non-carriers with regard to frequency of behavioural symptoms on the Neuropsychiatric Inventory-Questionnaire and severity of depressive symptoms on the Geriatric Depression Scale using generalized linear regression models with appropriate distributions and link functions. Results from the adjusted analyses indicated that depressive symptoms on the Neuropsychiatric Inventory-Questionnaire were less common in cognitively asymptomatic mutation carriers than in non-carriers (5% versus 17%, P = 0.014) and the odds of experiencing at least one behavioural sign in cognitively asymptomatic mutation carriers was lower than in non-carriers (odds ratio = 0.50, 95% confidence interval: 0.26-0.98, P = 0.042). Depression (56% versus 17%, P = 0.0003), apathy (40% versus 4%, P < 0.0001), disinhibition (16% versus 2%, P = 0.009), irritability (48% versus 9%, P = 0.0001), sleep changes (28% versus 7%, P = 0.003), and agitation (24% versus 6%, P = 0.008) were more common and

Is Myanmar jadeitite of Jurassic age? A result from incompletely recrystallized inherited zircon

NASA Astrophysics Data System (ADS)

Yui, Tzen-Fu; Fukoyama, Mayuko; Iizuka, Yoshiyuki; Wu, Chao-Ming; Wu, Tsai-Way; Liou, J. G.; Grove, Marty

2013-02-01

Zircons from two Myanmar jadeitite samples were separated for texture, mineral inclusion, U-Pb dating and trace element composition analyses. Three types of zircons, with respect to U-Pb isotope system, were recognized. Type I zircons are inherited ones, yielding an igneous protolith age of 160 ± 1 Ma; Type II zircons are metasomatic/hydrothermal ones, giving a (minimum) jadeitite formation age of 77 ± 3 Ma; and Type III zircons are incompletely recrystallized ones, with non-coherent and geologically meaningless ages from 153 to 105 Ma. These Myanmar jadeitites would therefore have formed through whole-sale metasomatic replacement processes. Compared with Type I zircons, Type II zircons show typical metasomatic/hydrothermal geochemical signatures, with low Th/U ratio (< 0.1), small Ce anomaly (Ce/Ce* = < 5) and low ΣREE content (40-115 ppm). Type III zircons, however, commonly have the above geochemical signatures straddle in between Type I and Type II zircons. It is shown that the resetting rates of various trace element compositions and U-Pb isotope system of inherited zircons are not coupled "in phase" in response to zircon recrystallization during jadeitite formation. The observed abnormally low Th/U ratio and small Ce anomaly of some Type I zircons, as well as the lack of negative Eu anomaly of all Type I zircons, should be suspected to be of secondary origin. In extreme cases, incompletely recrystallized zircons may show typical metasomatic/hydrothermal geochemical signatures, but leave U-Pb isotope system partially reset or even largely unchanged. Such zircons easily lead to incorrect age interpretation, and hence erroneous geological implication. The Myanmar jadeitites, based on the present study, might have formed during the Late Cretaceous subduction before the beginning of India-Asia continental collision at Paleocene. Previously proposed Late Jurassic ages for Myanmar jadeitites are suggested as results rooted on data retrieved from incompletely

Paternal inheritance in mealybugs (Hemiptera: Coccoidea: Pseudococcidae)

NASA Astrophysics Data System (ADS)

Kol-Maimon, Hofit; Mendel, Zvi; Franco, José Carlos; Ghanim, Murad

2014-10-01

Mealybugs have a haplodiploid reproduction system, with paternal genome elimination (PGE); the males are diploid soon after fertilization, but during embryogenesis, the male paternal set of chromosomes becomes heterochromatic (HC) and therefore inactive. Previous studies have suggested that paternal genes can be passed on from mealybug males to their sons, but not necessarily by any son, to the next generation. We employed crosses between two mealybug species— Planococcus ficus (Signoret) and Planococcus citri (Risso)—and between two populations of P. ficus, which differ in their mode of pheromone attraction, in order to demonstrate paternal inheritance from males to F2 through F1 male hybrids. Two traits were monitored through three generations: mode of male pheromone attraction (pherotype) and sequences of the internal transcribed spacer 2 (ITS2) gene segment (genotype). Our results demonstrate that paternal inheritance in mealybugs can occur from males to their F2 offspring, through F1 males (paternal line). F2 backcrossed hybrid males expressed paternal pherotypes and ITS2 genotypes although their mother originated through a maternal population. Further results revealed other, hitherto unknown, aspects of inheritance in mealybugs, such as that hybridization between the two species caused absence of paternal traits in F2 hybrid females produced by F1 hybrid females. Furthermore, hybridization between the two species raised the question of whether unattracted males have any role in the interactions between P. ficus and P. citri.

Environmentally induced epigenetic transgenerational inheritance of disease susceptibility.

PubMed

Nilsson, Eric E; Skinner, Michael K

2015-01-01

Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical characteristics and current therapies for inherited retinal degenerations.

PubMed

Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

2014-10-16

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307-316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod-cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone-rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Was Dinosaurian Physiology Inherited by Birds? Reconciling Slow Growth in Archaeopteryx

PubMed Central

Erickson, Gregory M.; Rauhut, Oliver W. M.; Zhou, Zhonghe; Turner, Alan H.; Inouye, Brian D.; Hu, Dongyu; Norell, Mark A.

2009-01-01

Background Archaeopteryx is the oldest and most primitive known bird (Avialae). It is believed that the growth and energetic physiology of basalmost birds such as Archaeopteryx were inherited in their entirety from non-avialan dinosaurs. This hypothesis predicts that the long bones in these birds formed using rapidly growing, well-vascularized woven tissue typical of non-avialan dinosaurs. Methodology/Principal Findings We report that Archaeopteryx long bones are composed of nearly avascular parallel-fibered bone. This is among the slowest growing osseous tissues and is common in ectothermic reptiles. These findings dispute the hypothesis that non-avialan dinosaur growth and physiology were inherited in totality by the first birds. Examining these findings in a phylogenetic context required intensive sampling of outgroup dinosaurs and basalmost birds. Our results demonstrate the presence of a scale-dependent maniraptoran histological continuum that Archaeopteryx and other basalmost birds follow. Growth analysis for Archaeopteryx suggests that these animals showed exponential growth rates like non-avialan dinosaurs, three times slower than living precocial birds, but still within the lowermost range for all endothermic vertebrates. Conclusions/Significance The unexpected histology of Archaeopteryx and other basalmost birds is actually consistent with retention of the phylogenetically earlier paravian dinosaur condition when size is considered. The first birds were simply feathered dinosaurs with respect to growth and energetic physiology. The evolution of the novel pattern in modern forms occurred later in the group's history. PMID:19816582

Phylogenetics Exercise Using Inherited Human Traits

ERIC Educational Resources Information Center

Tuimala, Jarno

2006-01-01

A bioinformatics laboratory exercise based on inherited human morphological traits is presented. It teaches how morphological characters can be used to study the evolutionary history of humans using parsimony. The exercise can easily be used in a pen-and-paper laboratory, but if computers are available, a more versatile analysis can be carried…

Expression and inheritance of sporophytic self-incompatibility in synthetic allohexaploid Senecio cambrensis (Asteraceae).

PubMed

Brennan, Adrian C; Hiscock, Simon J

2010-04-01

Allopolyploid speciation is common in plants and is frequently associated with shifts from outcrossing, for example self-incompatibility, to inbreeding (i.e. selfing). Senecio cambrensis is a recently evolved allohexaploid species that formed following hybridization between diploid self-incompatible S. squalidus and tetraploid self-compatible S. vulgaris. Studies of reproduction in wild populations of S. cambrensis have concluded that it is self-compatible. Here, we investigated self-compatibility in synthetic lines of S. cambrensis generated via hybridization and colchicine-induced polyploidization and wild S. cambrensis using controlled crossing experiments. Synthetic F(1)S. cambrensis individuals were all self-compatible but, in F(2) and later generations, self-incompatible individuals were identified at frequencies of 6.7-9.2%. Self-incompatibility was also detected in wild sampled individuals at a frequency of 12.2%. The mechanism and genetics of self-incompatibility were tested in synthetic S. cambrensis and found to be similar to those of its paternal parent S. squalidus (i.e. sporophytic). These results show, for the first time, that functional sporophytic self-incompatibility can be inherited and expressed in allopolyploids as early as the second (F(2)) generation. Wild S. cambrensis should therefore be considered as possessing a mixed mating system with the potential for evolution towards either inbreeding or outcrossing.

Does cross-generational epigenetic inheritance contribute to cultural continuity?

PubMed

Pembrey, Marcus E

2018-04-01

Human studies of cross-generational epigenetic inheritance have to consider confounding by social patterning down the generations, often referred to as 'cultural inheritance'. This raises the question to what extent is 'cultural inheritance' itself epigenetically mediated rather than just learnt. Human studies of non-genetic inheritance have demonstrated that, beyond foetal life, experiences occurring in mid-childhood before puberty are the most likely to be associated with cross-generational responses in the next generation(s). It is proposed that cultural continuity is played out along the axis, or 'payoff', between responsiveness and stability. During the formative years of childhood a stable family and/or home permits small children to explore and thereby learn. To counter disruptions to this family home ideal, cultural institutions such as local schools, religious centres and market places emerged to provide ongoing stability, holding the received wisdom of the past in an accessible state. This cultural support allows the growing child to freely indulge their responsiveness. Some of these prepubertal experiences induce epigenetic responses that also transfer molecular signals to the gametes through which they contribute to the conception of future offspring. In parallel co-evolution with growing cultural support for increasing responsiveness, 'runaway' responsiveness is countered by the positive selection of genetic variants that dampen responsiveness. Testing these ideas within longitudinal multigenerational cohorts will need information on ancestors/parents' own communities and experiences (Exposome scans) linked to ongoing Phenome scans on grandchildren; coupled with epigenome analysis, metastable epialleles and DNA methylation age. Interactions with genetic variants affecting responsiveness should help inform the broad hypothesis.

Assessment of Inheritance and Fitness Costs Associated with Field-Evolved Resistance to Cry3Bb1 Maize by Western Corn Rootworm.

PubMed

Paolino, Aubrey R; Gassmann, Aaron J

2017-05-11

The western corn rootworm, Diabrotica virgifera virgifera LeConte, is among the most serious insect pests of maize in North America. One strategy used to manage this pest is transgenic maize that produces one or more crystalline (Cry) toxins derived from the bacterium Bacillus thuringiensis (Bt). To delay Bt resistance by insect pests, refuges of non-Bt maize are grown in conjunction with Bt maize. Two factors influencing the success of the refuge strategy to delay resistance are the inheritance of resistance and fitness costs, with greater delays in resistance expected when inheritance of resistance is recessive and fitness costs are present. We measured inheritance and fitness costs of resistance for two strains of western corn rootworm with field-evolved resistance to Cry3Bb1 maize. Plant-based and diet-based bioassays revealed that the inheritance of resistance was non-recessive. In a greenhouse experiment, in which larvae were reared on whole maize plants in field soil, no fitness costs of resistance were detected. In a laboratory experiment, in which larvae experienced intraspecific and interspecific competition for food, a fitness cost of delayed larval development was identified, however, no other fitness costs were found. These findings of non-recessive inheritance of resistance and minimal fitness costs, highlight the potential for the rapid evolution of resistance to Cry3Bb1 maize by western corn rootworm, and may help to improve resistance management strategies for this pest.

Identification of Inherited Retinal Disease-Associated Genetic Variants in 11 Candidate Genes.

PubMed

Astuti, Galuh D N; van den Born, L Ingeborgh; Khan, M Imran; Hamel, Christian P; Bocquet, Béatrice; Manes, Gaël; Quinodoz, Mathieu; Ali, Manir; Toomes, Carmel; McKibbin, Martin; El-Asrag, Mohammed E; Haer-Wigman, Lonneke; Inglehearn, Chris F; Black, Graeme C M; Hoyng, Carel B; Cremers, Frans P M; Roosing, Susanne

2018-01-10

Inherited retinal diseases (IRDs) display an enormous genetic heterogeneity. Whole exome sequencing (WES) recently identified genes that were mutated in a small proportion of IRD cases. Consequently, finding a second case or family carrying pathogenic variants in the same candidate gene often is challenging. In this study, we searched for novel candidate IRD gene-associated variants in isolated IRD families, assessed their causality, and searched for novel genotype-phenotype correlations. Whole exome sequencing was performed in 11 probands affected with IRDs. Homozygosity mapping data was available for five cases. Variants with minor allele frequencies ≤ 0.5% in public databases were selected as candidate disease-causing variants. These variants were ranked based on their: (a) presence in a gene that was previously implicated in IRD; (b) minor allele frequency in the Exome Aggregation Consortium database (ExAC); (c) in silico pathogenicity assessment using the combined annotation dependent depletion (CADD) score; and (d) interaction of the corresponding protein with known IRD-associated proteins. Twelve unique variants were found in 11 different genes in 11 IRD probands. Novel autosomal recessive and dominant inheritance patterns were found for variants in Small Nuclear Ribonucleoprotein U5 Subunit 200 ( SNRNP200 ) and Zinc Finger Protein 513 ( ZNF513 ), respectively. Using our pathogenicity assessment, a variant in DEAH-Box Helicase 32 ( DHX32 ) was the top ranked novel candidate gene to be associated with IRDs, followed by eight medium and lower ranked candidate genes. The identification of candidate disease-associated sequence variants in 11 single families underscores the notion that the previously identified IRD-associated genes collectively carry > 90% of the defects implicated in IRDs. To identify multiple patients or families with variants in the same gene and thereby provide extra proof for pathogenicity, worldwide data sharing is needed.

Inheritance and world variation in thermal requirements for egg hatch in Lymantria dispar (Lepidoptera: Erebidae)

Treesearch

M.A. Keena

2016-01-01

Mode of inheritance of hatch traits in Lymantria dispar L. was determined by crossing populations nearly fixed for the phenotypic extremes. The nondiapausing phenotype was inherited via a single recessive gene and the phenotype with reduced low temperature exposure requirements before hatch was inherited via a single dominant gene. There was no...

Mapping of angular leaf spot resistance QTL in common bean (Phaseolus vulgaris L.) under different environments

PubMed Central

2012-01-01

Background Common bean (Phaseolus vulgaris L.) is the most important grain legume for human diet worldwide and the angular leaf spot (ALS) is one of the most devastating diseases of this crop, leading to yield losses as high as 80%. In an attempt to breed resistant cultivars, it is important to first understand the inheritance mode of resistance and to develop tools that could be used in assisted breeding. Therefore, the aim of this study was to identify quantitative trait loci (QTL) controlling resistance to ALS under natural infection conditions in the field and under inoculated conditions in the greenhouse. Results QTL analyses were made using phenotypic data from 346 recombinant inbreed lines from the IAC-UNA x CAL 143 cross, gathered in three experiments, two of which were conducted in the field in different seasons and one in the greenhouse. Joint composite interval mapping analysis of QTL x environment interaction was performed. In all, seven QTLs were mapped on five linkage groups. Most of them, with the exception of two, were significant in all experiments. Among these, ALS10.1DG,UC presented major effects (R2 between 16% - 22%). This QTL was found linked to the GATS11b marker of linkage group B10, which was consistently amplified across a set of common bean lines and was associated with the resistance. Four new QTLs were identified. Between them the ALS5.2 showed an important effect (9.4%) under inoculated conditions in the greenhouse. ALS4.2 was another major QTL, under natural infection in the field, explaining 10.8% of the variability for resistance reaction. The other QTLs showed minor effects on resistance. Conclusions The results indicated a quantitative inheritance pattern of ALS resistance in the common bean line CAL 143. QTL x environment interactions were observed. Moreover, the major QTL identified on linkage group B10 could be important for bean breeding, as it was stable in all the environments. Thereby, the GATS11b marker is a potential tool

Maternally-inherited diabetes with deafness (MIDD) and hyporeninemic hypoaldosteronism.

PubMed

Mory, Patricia B; Santos, Marcia C dos; Kater, Claudio E; Moisés, Regina S

2012-11-01

Maternally-inherited diabetes with deafness (MIDD) is a rare form of monogenic diabetes that results, in most cases, from an A-to-G transition at position 3243 of mitochondrial DNA (m.3243A>G) in the mitochondrial-encoded tRNA leucine (UUA/G) gene. As the name suggests, this condition is characterized by maternally-inherited diabetes and bilateral neurosensory hearing impairment. A characteristic of mitochondrial cytopathies is the progressive multisystemic involvement with the development of more symptoms during the course of the disease. We report here the case of a patient with MIDD who developed hyporeninemic hypoaldosteronism.

The intriguing complexity of parthenogenesis inheritance in Pilosella rubra (Asteraceae, Lactuceae).

PubMed

Rosenbaumová, Radka; Krahulcová, Anna; Krahulec, František

2012-09-01

Neither the genetic basis nor the inheritance of apomixis is fully understood in plants. The present study is focused on the inheritance of parthenogenesis, one of the basic elements of apomixis, in Pilosella (Asteraceae). A complex pattern of inheritance was recorded in the segregating F(1) progeny recovered from reciprocal crosses between the facultatively apomictic hexaploid P. rubra and the sexual tetraploid P. officinarum. Although both female and male reduced gametes of P. rubra transmitted parthenogenesis at the same rate in the reciprocal crosses, the resulting segregating F(1) progeny inherited parthenogenesis at different rates. The actual transmission rates of parthenogenesis were significantly correlated with the mode of origin of the respective F(1) progeny class. The inheritance of parthenogenesis was significantly reduced in F(1) n + n hybrid progeny from the cross where parthenogenesis was transmitted by female gametes. In F(1) n + 0 polyhaploid progeny from the same cross, however, the transmission rate of parthenogenesis was high; all fertile polyhaploids were parthenogenetic. It appeared that reduced female gametes transmitting parthenogenesis preferentially developed parthenogenetically and only rarely were fertilized in P. rubra. The fact that the determinant for parthenogenesis acts gametophytically in Pilosella and the precocious embryogenesis in parthenogenesis-transmitting megagametophytes was suggested as the most probable explanations for this observation. Furthermore, we observed the different expression of complete apomixis in the non-segregating F(1) 2n + n hybrids as compared to their apomictic maternal parent P. rubra. We suggest that this difference is a result of unspecified interactions between the parental genomes.

Genetic Screening for OPA1 and OPA3 Mutations in Patients with Suspected Inherited Optic Neuropathies

PubMed Central

Yu-Wai-Man, Patrick; Shankar, Suma P.; Biousse, Valérie; Miller, Neil R.; Bean, Lora J.H.; Coffee, Bradford; Hegde, Madhuri; Newman, Nancy J.

2010-01-01

Purpose Autosomal-dominant optic atrophy (DOA) is one of the most common inherited optic neuropathies, and it is genetically heterogeneous, with mutations in both OPA1 and OPA3 known to cause disease. About 60% of cases harbor OPA1 mutations, whereas OPA3 mutations have only been reported in two pedigrees with DOA and premature cataracts. The aim of this study was to determine the yield of OPA1 and OPA3 screening in a cohort of presumed DOA cases referred to a tertiary diagnostic laboratory. Design Retrospective case series. Participants One hundred and eighty-eight probands with bilateral optic atrophy referred for molecular genetic investigations at a tertiary diagnostic facility: 38 patients with an autosomal-dominant pattern of inheritance and 150 sporadic cases. Methods OPA1 and OPA3 genetic testing was initially performed using PCR-based sequencing methods. The presence of large-scale OPA1 and OPA3 genomic rearrangements was further assessed with a targeted comparative genomic hybridization (CGH) microarray platform. The three primary Leber hereditary optic neuropathy (LHON) mutations, m.3460G>A, m.11778G>A, and m.14484T>C, were also screened in all patients. Main Outcome Measures The proportion of patients with OPA1 and OPA3 pathogenic mutations. The clinical profile observed in molecularly confirmed DOA cases. Results We found 21 different OPA1 mutations in 27 of the 188 (14.4%) probands screened. The mutations included six novel pathogenic variants and the first reported OPA1 initiation codon mutation at c.1A>T. An OPA1 missense mutation, c.239A>G (p.Y80C), was identified in an 11-year-old African-American girl with optic atrophy and peripheral sensori-motor neuropathy in her lower limbs. The OPA1 detection rate was significantly higher among individuals with a positive family history of visual failure (50.0%) compared with sporadic cases (5.3%). The primary LHON screen was negative in our patient cohort, and additional molecular investigations did not

Obstetric outcomes of recurrent pregnancy loss patients diagnosed wıth inherited thrombophilia.

PubMed

Karadağ, C; Yoldemir, T; Karadağ, S D; İnan, C; Dolgun, Z N; Aslanova, L

2017-08-01

Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies. The relation between RPL and inherited thrombophilia requires anticoagulant therapy during pregnancy. However the obstetric outcomes have not been well defined in these RPL patients diagnosed with inherited thrombophilia, who have been given anticoagulant therapy. To investigate the obstetric outcomes in pregnant women with RPL who are given low molecular weight heparin (LMWH) and low-dose aspirin due to diagnosis of inherited thrombophilia. A hundred and eight RPL women were diagnosed with inherited thrombophilia, and 98 women were diagnosed with unexplained RPL. The patients with inherited thrombophilia were given LMWH and low-dose aspirin. Unexplained RPL patients were not given any medicine. The obstetric outcomes of participants were noted. In thrombophilic group, the live-birth levels were significantly higher [90 (83%) vs 67 (68%) p < 0.05], and the miscarriage levels were significantly lower than that in the control group [14 (13%) vs 27 (28%) p < 0.01]. The number of patients with preeclampsia was significantly higher in the thrombophilic group [16 (15%) vs 6 (6%) p < 0.05]. The number of preterm births was significantly higher than that of the controls [25 (23%) vs 10 (10%) p < 0.05]. The median gestation age of delivery was 35 weeks for thrombophilic patients and 38 weeks for controls (p < 0.05). The RPL patients diagnosed with inherited thrombophilia and who were given LMWH with low-dose aspirin had higher live-birth rates and lower miscarriage rates than those in the unexplained RPL patients. Increased risk of preeclampsia is seen in RPL patients with inherited thrombophilia despite thrombophilia prophylaxis.

Inheritance of proportionate dwarfism in Angus cattle.

PubMed

Latter, M R; Latter, B D H; Wilkins, J F; Windsor, P A

2006-04-01

To determine the mode of inheritance of congenital proportionate dwarfism in Angus and Angus crossbred cattle, initially detected in two commercial beef herds in northern New South Wales. Matings of normal carrier sires to unrelated cows of diverse breeds, and of one carrier sire to his unaffected daughters. An unrelated Piedmontese bull was also mated to unaffected daughters of the carrier sires. Two carrier Angus bulls and nine unaffected daughters, all of whom were completely indistinguishable from normal animals, were purchased for controlled breeding studies under known nutritional and disease conditions. Affected and carrier individuals were examined for the presence of obvious chromosomal abnormalities. Angus dwarfism has been successfully reproduced under controlled experimental conditions over successive years using unrelated dams and is undoubtedly heritable. The high frequency of occurrence of affected individuals (23/61 = 0.38 +/- .06) among the progeny of matings of the Angus sires to unrelated females of diverse breeding is not compatible with recessive inheritance, because of the negligible frequency of proportionate dwarfism in the breeds of the dams. Both paternal and maternal transmission of the defect was demonstrated, so that imprinting in the strict sense of a gene that is only expressed when received from the male parent appears not to be involved. Tested individuals showed no evidence of gross chromosomal abnormality. Dominant autosomal inheritance with incomplete penetrance was indicated by the lack of expression of the defective gene in the two Angus sires and in three unaffected daughters who produced dwarf calves from matings to the Piedmontese bull. The mode of inheritance is that of a single autosomal dominant gene with a penetrance coefficient of 0.75 +/- 0.12, estimated from the observed incidence of 23/61 affected offspring of the two carrier Angus bulls mated to unrelated dams. Simple genetic models involving either (i) an unstable

Difficulties in Learning Inheritance and Polymorphism

ERIC Educational Resources Information Center

Liberman, Neomi; Beeri, Catriel; Kolikant, Yifat Ben-David

2011-01-01

This article reports on difficulties related to the concepts of inheritance and polymorphism, expressed by a group of 22 in-service CS teachers with an experience with the procedural paradigm, as they coped with a course on OOP. Our findings are based on the analysis of tests, questionnaires that the teachers completed in the course, as well as on…

Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos

PubMed Central

Vázquez-Diez, Cayetana; Yamagata, Kazuo; Trivedi, Shardul; Haverfield, Jenna; FitzHarris, Greg

2016-01-01

Chromosome segregation defects in cancer cells lead to encapsulation of chromosomes in micronuclei (MN), small nucleus-like structures within which dangerous DNA rearrangements termed chromothripsis can occur. Here we uncover a strikingly different consequence of MN formation in preimplantation development. We find that chromosomes from within MN become damaged and fail to support a functional kinetochore. MN are therefore not segregated, but are instead inherited by one of the two daughter cells. We find that the same MN can be inherited several times without rejoining the principal nucleus and without altering the kinetics of cell divisions. MN motion is passive, resulting in an even distribution of MN across the first two cell lineages. We propose that perpetual unilateral MN inheritance constitutes an unexpected mode of chromosome missegregation, which could contribute to the high frequency of aneuploid cells in mammalian embryos, but simultaneously may serve to insulate the early embryonic genome from chromothripsis. PMID:26729872

Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos.

PubMed

Vázquez-Diez, Cayetana; Yamagata, Kazuo; Trivedi, Shardul; Haverfield, Jenna; FitzHarris, Greg

2016-01-19

Chromosome segregation defects in cancer cells lead to encapsulation of chromosomes in micronuclei (MN), small nucleus-like structures within which dangerous DNA rearrangements termed chromothripsis can occur. Here we uncover a strikingly different consequence of MN formation in preimplantation development. We find that chromosomes from within MN become damaged and fail to support a functional kinetochore. MN are therefore not segregated, but are instead inherited by one of the two daughter cells. We find that the same MN can be inherited several times without rejoining the principal nucleus and without altering the kinetics of cell divisions. MN motion is passive, resulting in an even distribution of MN across the first two cell lineages. We propose that perpetual unilateral MN inheritance constitutes an unexpected mode of chromosome missegregation, which could contribute to the high frequency of aneuploid cells in mammalian embryos, but simultaneously may serve to insulate the early embryonic genome from chromothripsis.

Inherited occipital hypoplasia/syringomyelia in the cavalier King Charles spaniel: experiences in setting up a worldwide DNA collection.

PubMed

Rusbridge, Clare; Knowler, Penny; Rouleau, Guy A; Minassian, Berge A; Rothuizen, Jan

2005-01-01

Inherited diseases commonly emerge within pedigree dog populations, often due to use of repeatedly bred carrier sire(s) within a small gene pool. Accurate family records are usually available making linkage analysis possible. However, there are many factors that are intrinsically difficult about collecting DNA and collating pedigree information from a large canine population. The keys to a successful DNA collection program include (1) the need to establish and maintain support from the pedigree breed clubs and pet owners; (2) committed individual(s) who can devote the considerable amount of time and energy to coordinating sample collection and communicating with breeders and clubs; and (3) providing means by which genotypic and phenotypic information can be easily collected and stored. In this article we described the clinical characteristics of inherited occipital hypoplasia/syringomyelia (Chiari type I malformation) in the cavalier King Charles spaniel and our experiences in establishing a pedigree and DNA database to study the disease.

A nonsense loss-of-function mutation in PCSK1 contributes to dominantly inherited human obesity.

PubMed

Philippe, J; Stijnen, P; Meyre, D; De Graeve, F; Thuillier, D; Delplanque, J; Gyapay, G; Sand, O; Creemers, J W; Froguel, P; Bonnefond, A

2015-02-01

A significant proportion of severe familial forms of obesity remain genetically elusive. Taking advantage of our unique cohort of multigenerational obese families, we aimed to assess the contribution of rare mutations in 29 common obesity-associated genes to familial obesity, and to evaluate in these families the putative presence of nine known monogenic forms of obesity. Through next-generation sequencing, we sequenced the coding regions of 34 genes involved in polygenic and/or monogenic forms of obesity in 201 participants (75 normal weight individuals, 54 overweight individuals and 72 individuals with obesity class I, II or III) from 13 French families. In vitro functional analyses were performed to investigate the mutation PCSK1-p.Arg80* which was identified in a family. A novel heterozygous nonsense variant in PCSK1 (p.Arg80*), encoding a propeptide truncated to less than two exons (out of 14), was found to co-segregate with obesity in a three-generation family. We demonstrated that this mutation inhibits PCSK1 enzyme activity and that this inhibition most likely does not involve a strong physical interaction. Furthermore, both mutations PCSK1-p.Asn180Ser and POMC-p.Phe144Leu, which had previously been reported to be associated with severe obesity, were also identified in this study, but did not co-segregate with obesity. Finally, we did not identify any rare mutations co-segregating with obesity in common obesity susceptibility genes, except for CADM2 and QPCTL, where we found two novel variants (p.Arg81His and p.Leu98Pro, respectively) in three obese individuals. We showed for the first time that a nonsense mutation in PCSK1 was likely to cause dominantly inherited human obesity, due to the inhibiting properties of the propeptide fragment encoded by the null allele. Furthermore, the present family sequencing design challenged the contribution of previously reported mutations to monogenic or at least severe obesity.

CRISPR-Cas9 genome engineering: Treating inherited retinal degeneration.

PubMed

Burnight, Erin R; Giacalone, Joseph C; Cooke, Jessica A; Thompson, Jessica R; Bohrer, Laura R; Chirco, Kathleen R; Drack, Arlene V; Fingert, John H; Worthington, Kristan S; Wiley, Luke A; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

2018-03-22

Gene correction is a valuable strategy for treating inherited retinal degenerative diseases, a major cause of irreversible blindness worldwide. Single gene defects cause the majority of these retinal dystrophies. Gene augmentation holds great promise if delivered early in the course of the disease, however, many patients carry mutations in genes too large to be packaged into adeno-associated viral vectors and some, when overexpressed via heterologous promoters, induce retinal toxicity. In addition to the aforementioned challenges, some patients have sustained significant photoreceptor cell loss at the time of diagnosis, rendering gene replacement therapy insufficient to treat the disease. These patients will require cell replacement to restore useful vision. Fortunately, the advent of induced pluripotent stem cell and CRISPR-Cas9 gene editing technologies affords researchers and clinicians a powerful means by which to develop strategies to treat patients with inherited retinal dystrophies. In this review we will discuss the current developments in CRISPR-Cas9 gene editing in vivo in animal models and in vitro in patient-derived cells to study and treat inherited retinal degenerative diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

The retina/RPE proteome in chick myopia and hyperopia models: Commonalities with inherited and age-related ocular pathologies

PubMed Central

Riddell, Nina; Faou, Pierre; Murphy, Melanie; Giummarra, Loretta; Downs, Rachael A.; Rajapaksha, Harinda

2017-01-01

.90 D ± 0.37 D were evident in the negative and positive lens groups, respectively, at 6 h. By 48 h, refractive compensation to both lens types was almost complete (negative lens −9.70 D ± 0.41 D, positive lens 7.70 D ± 0.44 D). More than 140 differentially abundant proteins were identified in each lens group relative to the no lens controls at both time points. No proteins were differentially abundant between the negative and positive lens groups at 6 h, and 13 were differentially abundant at 48 h. As there was substantial overlap in the proteins implicated across the six comparisons, a total of 390 differentially abundant proteins were identified. Sixty-five of these 390 proteins had previously been implicated in transcriptome studies of refractive error animal models, and 42 had previously been associated with AMD, choroidal neovascularization, glaucoma, and/or cataract in humans. The overlap of differentially abundant proteins with AMD-associated genes and proteins was statistically significant for all conditions (Benjamini-Hochberg adjusted p<0.05), with over-representation analysis implicating ontologies related to oxidative stress, cholesterol homeostasis, and melanin biosynthesis. GSEA identified significant enrichment of genes associated with abnormal electroretinogram, photophobia, and nyctalopia phenotypes in the proteins negatively correlated with ocular refraction across the lens groups at 6 h. The implicated proteins were primarily linked to photoreceptor dystrophies and mitochondrial disorders in humans. Conclusions Optical defocus in the chicks induces rapid changes in the abundance of many proteins in the retina/RPE that have previously been linked to inherited and age-related ocular pathologies in humans. Similar changes have been identified in a meta-analysis of chick refractive error transcriptome studies, highlighting the chick as a model for the study of optically induced stress with possible relevance to understanding the development of a

Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

PubMed Central

Yu-Wai-Man, Patrick

2016-01-01

Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. PMID:27002113

Insurance coverage of medical foods for treatment of inherited metabolic disorders

PubMed Central

Berry, Susan A.; Kenney, Mary Kay; Harris, Katharine B.; Singh, Rani H.; Cameron, Cynthia A.; Kraszewski, Jennifer N.; Levy-Fisch, Jill; Shuger, Jill F.; Greene, Carol L.; Lloyd-Puryear, Michele A.; Boyle, Coleen A.

2015-01-01

Purpose Treatment of inherited metabolic disorders is accomplished by use of specialized diets employing medical foods and medically necessary supplements. Families seeking insurance coverage for these products express concern that coverage is often limited; the extent of this challenge is not well defined. Methods To learn about limitations in insurance coverage, parents of 305 children with inherited metabolic disorders completed a paper survey providing information about their use of medical foods, modified low-protein foods, prescribed dietary supplements, and medical feeding equipment and supplies for treatment of their child's disorder as well as details about payment sources for these products. Results Although nearly all children with inherited metabolic dis orders had medical coverage of some type, families paid “out of pocket” for all types of products. Uncovered spending was reported for 11% of families purchasing medical foods, 26% purchasing supplements, 33% of those needing medical feeding supplies, and 59% of families requiring modified low-protein foods. Forty-two percent of families using modified low-protein foods and 21% of families using medical foods reported additional treatment-related expenses of $100 or more per month for these products. Conclusion Costs of medical foods used to treat inherited metabolic disorders are not completely covered by insurance or other resources. PMID:23598714

Simultaneous Occurence of an Autosomal Dominant Inherited MSX1 Mutation and an X-linked Recessive Inherited EDA Mutation in One Chinese Family with Non-syndromic Oligodontia.

PubMed

Zhang, Xiao Xia; Wong, Sing Wai; Han, Dong; Feng, Hai Lan

2015-01-01

To describe the simultaneous occurence of an autosomal dominant inherited MSX1 mutation and an X-linked recessive inherited EDA mutation in one Chinese family with nonsyndromic oligodontia. Clinical data of characteristics of tooth agenesis were collected. MSX1 and EDA gene mutations were detected in a Chinese family of non-syndromic oligodontia. Mild hypodontia in the parents and severe oligodontia in the son was recorded. A novel missense heterozygous mutation c.517C>A (p.Arg173Ser) was detected in the MSX1 gene in the boy and the father. A homozygous missense mutation c.1001G>A (p.Arg334His) was detected in the EDA gene in the boy and the same mutant occurred heterozygously in the mother. Simultaneous occurence of two different gene mutations with different inheritence patterns, which both caused oligodontia, which occurred in one subject and in one family, was reported.

Crowd-sourced Ontology for Photoleukocoria: Identifying Common Internet Search Terms for a Potentially Important Pediatric Ophthalmic Sign.

PubMed

Staffieri, Sandra E; Kearns, Lisa S; Sanfilippo, Paul G; Craig, Jamie E; Mackey, David A; Hewitt, Alex W

2018-02-01

Leukocoria is the most common presenting sign for pediatric eye disease including retinoblastoma and cataract, with worse outcomes if diagnosis is delayed. We investigated whether individuals could identify leukocoria in photographs (photoleukocoria) and examined their subsequent Internet search behavior. Using a web-based questionnaire, in this cross-sectional study we invited adults aged over 18 years to view two photographs of a child with photoleukocoria, and then search the Internet to determine a possible diagnosis and action plan. The most commonly used search terms and websites accessed were recorded. The questionnaire was completed by 1639 individuals. Facebook advertisement was the most effective recruitment strategy. The mean age of all respondents was 38.95 ± 14.59 years (range, 18-83), 94% were female, and 59.3% had children. An abnormality in the images presented was identified by 1613 (98.4%) participants. The most commonly used search terms were: "white," "pupil," "photo," and "eye" reaching a variety of appropriate websites or links to print or social media articles. Different words or phrases were used to describe the same observation of photoleukocoria leading to a range of websites. Variations in the description of observed signs and search words influenced the sites reached, information obtained, and subsequent help-seeking intentions. Identifying the most commonly used search terms for photoleukocoria is an important step for search engine optimization. Being directed to the most appropriate websites informing of the significance of photoleukocoria and the appropriate actions to take could improve delays in diagnosis of important pediatric eye disease such as retinoblastoma or cataract.

Detection of Human Herpesvirus 6B (HHV-6B) Reactivation in Hematopoietic Cell Transplant Recipients with Inherited Chromosomally Integrated HHV-6A by Droplet Digital PCR.

PubMed

Sedlak, Ruth Hall; Hill, Joshua A; Nguyen, Thuy; Cho, Michelle; Levin, Greg; Cook, Linda; Huang, Meei-Li; Flamand, Louis; Zerr, Danielle M; Boeckh, Michael; Jerome, Keith R

2016-05-01

The presence of inherited chromosomally integrated human herpesvirus 6 (ciHHV-6) in hematopoietic cell transplant (HCT) donors or recipients confounds molecular testing for HHV-6 reactivation, which occurs in 30 to 50% of transplants. Here we describe a multiplex droplet digital PCR clinical diagnostic assay that concurrently distinguishes between HHV-6 species (A or B) and identifies inherited ciHHV-6. By applying this assay to recipient post-HCT plasma and serum samples, we demonstrated reactivation of HHV-6B in 25% (4/16 recipients) of HCT recipients with donor- or recipient-derived inherited ciHHV-6A, underscoring the need for diagnostic testing for HHV-6 infection even in the presence of ciHHV-6. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Inheritance and intergenerational wealth transmission in eighteenth-century Ottoman Kastamonu: an empirical investigation.

PubMed

Ergene, Boğaç A; Berker, Ali

2009-01-01

This article investigates the relationship between inheritance and wealth in the context of eighteenth-century Ottoman Kastamonu. Based on the estate inventories of the deceased (sing. tereke) as recorded in Kastamonu court records (sicils), the article introduces a variety of quantitative techniques to measure the impact of Islamic inheritance practices on wealth accumulation across subsequent generations and to understand how it influenced wealth mobility among various socioeconomic groups. The estimations provided in this article suggest that while the inheritance practice in Kastamonu caused wealth fragmentation, the process also contributed to the durability of economic divisions within the provincial Ottoman society.

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) caused by a VDR mutation: A novel mechanism of dominant inheritance.

PubMed

Isojima, Tsuyoshi; Ishizawa, Michiyasu; Yoshimura, Kazuko; Tamura, Mayuko; Hirose, Shinichi; Makishima, Makoto; Kitanaka, Sachiko

2015-06-01

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the VDR gene, and its inheritance is autosomal recessive. In this report, we aimed to confirm whether HVDRR is occasionally inherited as a dominant trait. An 18-month-old Japanese boy was evaluated for short stature and bowlegs. His father had been treated for rickets during childhood, and his paternal grandfather had bowlegs. We diagnosed him with HVDRR based on laboratory data and radiographic evidence of rickets. Sequence analyses of VDR were performed, and the functional consequences of the detected mutations were analyzed for transcriptional activity, ligand binding, and interaction with the retinoid X receptor, cofactors, and the vitamin D response element (VDRE). A novel mutation (Q400LfsX7) and a reported variant (R370H) were identified in the patient. Heterozygous Q400LfsX7 was detected in his father, and heterozygous R370H was detected in his healthy mother. Functional studies revealed that the transcriptional activity of Q400LfsX7-VDR was markedly disturbed. The mutant had a dominant-negative effect on wild-type-VDR, and the ligand binding affinity of Q400LfsX7-VDR was completely impaired. Interestingly, Q400LfsX7-VDR had a strong interaction with corepressor NCoR and could interact with VDRE without the ligand. R370H-VDR was functionally similar to wild-type-VDR. In conclusion, we found a dominant-negative mutant of VDR causing dominantly inherited HVDRR through a constitutive corepressor interaction, a mechanism similar to that in dominantly inherited thyroid hormone receptor mutations. Our report together with a reported pedigree suggested a distinct inheritance of HVDRR and enriched our understanding of VDR abnormalities.

Integrative Analysis to Identify Common Genetic Markers of Metabolic Syndrome, Dementia, and Diabetes

PubMed Central

Zhang, Weihong; Xin, Linlin; Lu, Ying

2017-01-01

Background Emerging data have established links between systemic metabolic dysfunction, such as diabetes and metabolic syndrome (MetS), with neurocognitive impairment, including dementia. The common gene signature and the associated signaling pathways of MetS, diabetes, and dementia have not been widely studied. Material/Methods We exploited the translational bioinformatics approach to choose the common gene signatures for both dementia and MetS. For this we employed “DisGeNET discovery platform”. Results Gene mining analysis revealed that a total of 173 genes (86 genes common to all three diseases) which comprised a proportion of 43% of the total genes associated with dementia. The gene enrichment analysis showed that these genes were involved in dysregulation in the neurological system (23.2%) and the central nervous system (20.8%) phenotype processes. The network analysis revealed APOE, APP, PARK2, CEPBP, PARP1, MT-CO2, CXCR4, IGFIR, CCR5, and PIK3CD as important nodes with significant interacting partners. The meta-regression analysis showed modest association of APOE with dementia and metabolic complications. The directionality of effects of the variants on Alzheimer disease is generally consistent with previous observations and did not differ by race/ethnicity (p>0.05), although our study had low power for this test. Conclusions Our novel approach showed APOE as a common gene signature with a link to dementia, MetS, and diabetes. Future gene association studies should focus on the association of gene polymorphisms with multiple disease models to identify novel putative drug targets. PMID:29229897

Inheritance of high levels of resistance to common bacterial blight caused by Xanthomonas Axonopodis pv. Phaseoli in common bean (Phaseolus vulgaris L.)

USDA-ARS?s Scientific Manuscript database

Common bacterial blight caused by the pathogen Xanthomonas axonopodis pv. phaseoli (Xap) is an important biotic factor limiting common bean (Phaseolus vulgaris L.) production. A few interspecific bean breeding lines such as VAX 6 exhibit a high level of resistance to a wide range of Xap strains repr...

Common Allergens Identified Based on Patch Test Results in Patients with Suspected Contact Dermatitis of the Scalp

PubMed Central

Aleid, Nouf M.; Fertig, Raymond; Maddy, Austin; Tosti, Antonella

2017-01-01

Background Contact dermatitis of the scalp is common and might be caused by many chemicals including metals, ingredients of shampoos and conditioners, dyes, or other hair treatments. Eliciting a careful history and patch tests are necessary to identify the responsible allergen and prevent relapses. Objectives To identify allergens that may cause contact dermatitis of the scalp by reviewing patch test results. Methods We reviewed the records of 1,015 patients referred for patch testing at the Dermatology Department of the University of Miami. A total of 226 patients (205 females and 21 males) with suspected scalp contact dermatitis were identified, and the patch test results and clinical data for those patients were analyzed. Most patients were referred for patch testing from a specialized hair clinic at our institution. Results The most common allergens in our study population were nickel (23.8%), cobalt (21.0%), balsam of Peru (18.2%), fragrance mix (14.4%), carba mix (11.6%), and propylene glycol (PG) (8.8%). The majority of patients were females aged 40–59 years, and scalp itching or burning were reported as the most common symptom. Conclusion Frequent sources of allergens for metals include hair clasps, pins, and brushes, while frequent sources of allergens for preservatives, fragrance mix, and balsam of Peru include shampoos, conditioners, and hair gels. Frequent sources of allergens for PG include topical medications. PMID:28611994

Fine mapping of a dominantly inherited powdery mildew resistance major-effect QTL, Pm1.1, in cucumber identifies a 41.1 kb region containing two tandemly arrayed cysteine-rich receptor-like protein kinase genes.

PubMed

Xu, Xuewen; Yu, Ting; Xu, Ruixue; Shi, Yang; Lin, Xiaojian; Xu, Qiang; Qi, Xiaohua; Weng, Yiqun; Chen, Xuehao

2016-03-01

A dominantly inherited major-effect QTL for powdery mildew resistance in cucumber was fine mapped. Two tandemly arrayed cysteine-rich receptor-like protein kinase genes were identified as the most possible candidates. Powdery mildew (PM) is one of the most severe fungal diseases of cucumber (Cucumis sativus L.) and other cucurbit crops, but the molecular genetic mechanisms of powdery mildew resistance in cucurbits are still poorly understood. In this study, through marker-assisted backcrossing with an elite cucumber inbred line, D8 (PM susceptible), we developed a single-segment substitution line, SSSL0.7, carrying 95 kb fragment from PM resistance donor, Jin5-508, that was defined by two microsatellite markers, SSR16472 and SSR16881. A segregating population with 3600 F2 plants was developed from the SSSL0.7 × D8 mating; segregation analysis confirmed a dominantly inherited major-effect QTL, Pm1.1 in cucumber chromosome 1 underlying PM resistance in SSSL0.7. New molecular markers were developed through exploring the next generation resequenced genomes of Jin5-508 and D8. Linkage analysis and QTL mapping in a subset of the F2 plants delimited the Pm1.1 locus into a 41.1 kb region, in which eight genes were predicted. Comparative gene expression analysis revealed that two concatenated genes, Csa1M064780 and Csa1M064790 encoding the same function of a cysteine-rich receptor-like protein kinase, were the most likely candidate genes. GFP fusion protein-aided subcellular localization indicated that both candidate genes were located in the plasma membrane, but Csa1M064780 was also found in the nucleus. This is the first report of dominantly inherited PM resistance in cucumber. Results of this study will provide new insights into understanding the phenotypic and genetic mechanisms of PM resistance in cucumber. This work should also facilitate marker-assisted selection in cucumber breeding for PM resistance.

Multiple ways to prevent transmission of paternal mitochondrial DNA for maternal inheritance in animals.

PubMed

Sato, Ken; Sato, Miyuki

2017-10-01

Mitochondria contain their own DNA (mtDNA). In most sexually reproducing organisms, mtDNA is inherited maternally (uniparentally); this type of inheritance is thus referred to as 'maternal (uniparental) inheritance'. Recent studies have revealed various mechanisms to prevent the transmission of sperm-derived paternal mtDNA to the offspring, thereby ensuring maternal inheritance of mtDNA. In the nematode Caenorhabditis elegans, paternal mitochondria and their mtDNA degenerate almost immediately after fertilization and are selectively degraded by autophagy, which is referred to as 'allophagy' (allogeneic [non-self] organelle autophagy). In the fruit fly Drosophila melanogaster, paternal mtDNA is largely eliminated by an endonuclease G-mediated mechanism. Paternal mitochondria are subsequently removed by endocytic and autophagic pathways after fertilization. In many mammals, including humans, paternal mitochondria enter fertilized eggs. However, the fate of paternal mitochondria and their mtDNA in mammals is still a matter of debate. In this review, we will summarize recent knowledge on the molecular mechanisms underlying the prevention of paternal mtDNA transmission, which ensures maternal mtDNA inheritance in animals. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

[Application of qualitative interviews in inheritance research of famous old traditional Chinese medicine doctors: ideas and experience].

PubMed

Luo, Jing; Fu, Chang-geng; Xu, Hao

2015-04-01

The inheritance of famous old traditional Chinese medicine (TCM) doctors plays an essential role in the fields of TCM research. Qualitative interviews allow for subjectivity and individuality within clinical experience as well as academic ideas of doctors, making it a potential appropriate research method for inheritance of famous old TCM doctors. We summarized current situations of inheritance research on famous old TCM doctors, and then discussed the feasibility of applying qualitative interviews in inheritance of famous old TCM doctors. By combining our experience in research on inheritance of famous old TCM doctors, we gave some advice on study design, interview implementation, data transcription and analyses , and report writing, providing a reference for further relevant research.

Countering the New Media: The Resurgence of Inheritance Effects in Primetime Network Television.

ERIC Educational Resources Information Center

Davis, Donald M.; Walker, James R.

A study examined the impact of remote control devices, videocassette recorders, and cable television on inheritance effects (the tendency for viewers to continue watching a channel at the conclusion of a program). Inheritance effects were measured by calculating the correlation between program share and lead-in program share for all primetime…

Fitness and inheritance of metaflumizone resistance in Plutella xylostella.

PubMed

Shen, Jun; Li, Dongyang; Zhang, Shuzhen; Zhu, Xun; Wan, Hu; Li, Jianhong

2017-06-01

The diamondback moth, Plutella xylostella (L.) has developed resistance to many types of insecticides in the field. To study inheritance and fitness cost of metaflumizone resistance, a susceptible strain of diamondback moth was continuously selected with metaflumizone during 37 generations under laboratory conditions. The resistance to metaflumizone was at a high level (resistance ratios from 250.37 to 1450.47-fold). We investigated a metaflumizone resistance strain (G 27 ) and a susceptible strain of P. xylostella, using the age-stage, two-sex life table approach. Compared to the susceptible strain, egg duration, the developmental time of the first and second instar larvae, pupae duration, adult preoviposition period (APOP), total preoviposition period (TPOP), egg hatchability, the survival rate of second instar larva and the mean generation time (T) were significantly differences in the resistant strain. The resistant strain had a relative fitness of 0.78. The inheritance of metaflumizone resistance was also studied by crossing the metaflumizone resistant and susceptible populations. Results revealed an autosomal and incompletely recessive mode of inheritance for metaflumizone resistance in the resistant population of P. xylostella. The present study provided useful information for planning potential management strategies to delay development of metaflumizone resistance in P. xylostella. Copyright © 2017 Elsevier Inc. All rights reserved.

Middle school students' learning about genetic inheritance through on-line scaffolding supports

NASA Astrophysics Data System (ADS)

Manokore, Viola

valuable as there were no significant differences in test scores between students who interacted with different unit versions, F(1, 141) = 3.35, p = 0.07. However, there was a significant difference between test scores of students who had different teachers, F (1, 141) = 12.51, p = 0.001. Furthermore, apart from scoring for scientific accuracy, responses were also examined to establish whether students held some of the conceptions reported in literature about genetic inheritance. Where possible, attempts were made to identify whether students were using evidence from the unit or their out-of-school experiences in their responses to the scaffolding support prompts. It was evident that about half of the students attributed most of their inherited traits to a specific parent they resemble for that trait. In this dissertation study, the term students' resemblance theory was used to refer to the aforementioned students' reasoning. Additional, I argue that students' resemblance theory may be used to explain students' thinking when they incorrectly believe that boys or girls inherit more genes from their father or mother based on gender resemblance. Consequently, I argued that students' resemblance theory may influence students' learning and understanding about Mendel's law of segregation which include the following principles; genes exist in more than one form, offspring inherit two alleles for each trait, allele pairs separate during meiosis and alleles can be recessive or dominant. This study documented students' conceptions related to Mendel's law of segregation.

Somatic APC mosaicism and oligogenic inheritance in genetically unsolved colorectal adenomatous polyposis patients.

PubMed

Ciavarella, Michele; Miccoli, Sara; Prossomariti, Anna; Pippucci, Tommaso; Bonora, Elena; Buscherini, Francesco; Palombo, Flavia; Zuntini, Roberta; Balbi, Tiziana; Ceccarelli, Claudio; Bazzoli, Franco; Ricciardiello, Luigi; Turchetti, Daniela; Piazzi, Giulia

2018-03-01

Germline variants in the APC gene cause familial adenomatous polyposis. Inherited variants in MutYH, POLE, POLD1, NTHL1, and MSH3 genes and somatic APC mosaicism have been reported as alternative causes of polyposis. However, ~30-50% of cases of polyposis remain genetically unsolved. Thus, the aim of this study was to investigate the genetic causes of unexplained adenomatous polyposis. Eight sporadic cases with >20 adenomatous polyps by 35 years of age or >50 adenomatous polyps by 55 years of age, and no causative germline variants in APC and/or MutYH, were enrolled from a cohort of 56 subjects with adenomatous colorectal polyposis. APC gene mosaicism was investigated on DNA from colonic adenomas by Sanger sequencing or Whole Exome Sequencing (WES). Mosaicism extension to other tissues (peripheral blood, saliva, hair follicles) was evaluated using Sanger sequencing and/or digital PCR. APC second hit was investigated in adenomas from mosaic patients. WES was performed on DNA from peripheral blood to identify additional polyposis candidate variants. We identified APC mosaicism in 50% of patients. In three cases mosaicism was restricted to the colon, while in one it also extended to the duodenum and saliva. One patient without APC mosaicism, carrying an APC in-frame deletion of uncertain significance, was found to harbor rare germline variants in OGG1, POLQ, and EXO1 genes. In conclusion, our restrictive selection criteria improved the detection of mosaic APC patients. In addition, we showed for the first time that an oligogenic inheritance of rare variants might have a cooperative role in sporadic colorectal polyposis onset.

Observations and controls on the occurrence of inherited zircon in Concord-type granitoids, New Hampshire

USGS Publications Warehouse

Harrison, T.M.; Aleinikoff, J.N.; Compston, W.

1987-01-01

U-Pb analyses of zircons separated from two Concord-type plutons near Sunapee and Dixville Notch, New Hampshire, reveal differences in the pattern and magnitude of zircon inheritance which are related to differences in melt chemistry. The Sunapee pluton contains only slightly more Zr than required to saturate the melt at the peak temperature of 700 ?? 30??C. Traces of inherited zircon in this separate are inferred to be present as small, largely resorbed grains. In contrast, the Long Mountain pluton, near Dixville Notch, contains about 240% more Zr than required to saturate the melt. Thus, more than half of the Zr existed as stable, inherited zircon crystals during the partial fusion event, consistent with the observation of substantial inheritance in all grain size fractions. Ion probe intra-grain analyses of zircon from the Long Mountain pluton indicate a complex pattern of inheritance with contributions from at least two Proterozoic terrenes and caution against simple interpretations of upper and lower intercepts of chords containing an inherited component. Ion probe analyses of zircons from the Sunapee pluton reveal clear evidence of U loss which results in incorrect apparent conventional U-Pb ages. Ages of crystallization for the Long Mountain and Sunapee pluton are ~350 and 354 ?? 5 Ma, respectively. A Sm/Nd measurement for the Long Mountain pluton yields a depleted mantle model age of 1.5 Ga, consistent with the observed inheritance pattern. In contrast, a Sm/Nd model age for the Sunapee pluton is improbably old due to minor monazite fractionation. ?? 1987.

Evidence for major gene inheritance of Alzheimer disease in families of patients with and without Apolipoprotein E {epsilon}4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, V.S.; Auerbach, S.A.; Farrer, L.A.

1996-09-01

Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total groupmore » of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one {epsilon}4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking E4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband`s APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility. 76 refs., 4 tabs.« less

Dominant inheritance of cerebral gigantism.

PubMed

Zonana, J; Sotos, J F; Romshe, C A; Fisher, D A; Elders, M J; Rimoin, D L

1977-08-01

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

Multigenerational Inheritance of Long QT Syndrome Type 2 in a Japanese Family.

PubMed

Ichikawa, Mari; Ohno, Seiko; Fujii, Yusuke; Ozawa, Junichi; Sonoda, Keiko; Fukuyama, Megumi; Kato, Koichi; Kimura, Hiromi; Itoh, Hideki; Hayashi, Hideki; Horie, Minoru

2016-01-01

Congenital long QT syndrome (LQTS) is an important cause of sudden cardiac death in young people without any other structural disease. Mutations in the genes encoding the cardiac ion channels or associated proteins have been shown to result in ion channel dysfunction and thereby causing LQTS. We investigated a Japanese family with LQTS for four generations, with the female family members showing severe symptoms. We performed genetic tests for LQTS-related genes and identified a heterozygous KCNH2 mutation (p.K638del). In the family, the KCNH2 mutation had a very high multigenerational inheritance, and female genotype positives showed more severe phenotypes.

Understanding Genetics and Inheritance in Rural Schools

ERIC Educational Resources Information Center

Kibuka-Sebitosi, Esther

2007-01-01

Conducted in urban and rural schools in two provinces of South Africa, the present study reports biology learners' understanding of concepts about genetics and inheritance. Participants were Grade 11 and 12 learners, aged 15-16 years. The tools included a written questionnaire, interviews, pre- and post-paper and pencil tests and focus group…

Intergenerational transfers in Philippine rice villages. Gender differences in traditional inheritance customs.

PubMed

Quisumbing, A R

1994-04-01

The author presents findings from a study of education, land, and nonland asset transfers from parents to children in 344 households in five rice villages in the Philippines. A model with family fixed effects is developed which explains transfers better than either individual heterogeneity or observed parent and child characteristics without family fixed effects. Analysis revealed that families facing different land constraints exhibit significantly different patterns of educational investment in children. In a subsample with completed inheritance, daughters receive less education, land, and total inheritance, but are compensated with nonland assets. Parents also exhibit preferential behavior toward children of the same gender such that daughters of better educated mothers receive more land, nonland assets, and total inheritance. Better educated fathers, however, give land preferentially to sons, but favor daughters in education.

The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease

PubMed Central

Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-ha; Wigler, Michael; Levy, Dan

2013-01-01

Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable pheno-types and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo. PMID:23979609

The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease.

PubMed

Warburton, Dorothy; Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-Yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-Ha; Wigler, Michael; Levy, Dan

2014-01-01

Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable phenotypes and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo.

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

PubMed Central

Gala, Manish; Abecasis, Goncalo; Bezieau, Stephane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Conti, David V.; Curtis, Keith R.; Duggan, David; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Leal, Suzanne M.; Newcomb, Polly A.; Nickerson, Deborah A.; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Hsu, Li; Chan, Andrew T.; White, Emily; Berndt, Sonja I.; Peters, Ulrike

2016-01-01

Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s). PMID:27379672

Combined prevalence of inherited skeletal disorders in dog breeds in Belgium.

PubMed

Coopman, F; Broeckx, B; Verelst, E; Deforce, D; Saunders, J; Duchateau, L; Verhoeven, G

2014-01-01

Canine hip dysplasia (CHD), canine elbow dysplasia (CED), and humeral head osteochondrosis (HHOC) are inherited traits with uneven incidence in dog breeds. Knowledge of the combined prevalence of these three disorders is necessary to estimate the effect of the currently applied breeding strategies, in order to improve the genetic health of the population. Official screening results of the Belgian National Committee for Inherited Skeletal Disorders (NCSID) revealed that an average of 31.8% (CHD, CED, or both; n = 1273 dogs) and 47.2% (CHD, CED, HHOC, or a combination of these three diseases; n = 250 dogs) of dogs are mildly to severely affected by at least one skeletal disorder. According to the current breeding recommendations in some dog breeds in Belgium, these animals should be restricted (mild signs) or excluded (moderate to severe signs) from breeding. The introduction of genetic parameters, such as estimated breeding values, might create a better approach to gradually reduce the incidence of these complex inherited joint disorders, without compromising genetic population health.

Plan of Action for Inherited Cardiovascular Diseases: Synthesis of Recommendations and Action Algorithms.

PubMed

Barriales-Villa, Roberto; Gimeno-Blanes, Juan Ramón; Zorio-Grima, Esther; Ripoll-Vera, Tomás; Evangelista-Masip, Artur; Moya-Mitjans, Angel; Serratosa-Fernández, Luis; Albert-Brotons, Dimpna C; García-Pinilla, José Manuel; García-Pavía, Pablo

2016-03-01

The term inherited cardiovascular disease encompasses a group of cardiovascular diseases (cardiomyopathies, channelopathies, certain aortic diseases, and other syndromes) with a number of common characteristics: they have a genetic basis, a familial presentation, a heterogeneous clinical course, and, finally, can all be associated with sudden cardiac death. The present document summarizes some important concepts related to recent advances in sequencing techniques and understanding of the genetic bases of these diseases. We propose diagnostic algorithms and clinical practice recommendations and discuss controversial aspects of current clinical interest. We highlight the role of multidisciplinary referral units in the diagnosis and treatment of these conditions. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Inherited Disorders of Bilirubin Clearance

PubMed Central

Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

2016-01-01

Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

[Mitochondria inheritance in yeast saccharomyces cerevisiae].

PubMed

Fizikova, A Iu

2011-01-01

The review is devoted to the main mechanisms of mitochondria inheritance in yeast Saccharonmyces cerevisiae. The genetic mechanisms of functionally active mitochondria inheritance in eukaryotic cells is one of the most relevant in modem researches. A great number of genetic diseases are associated with mitochondria dysfunction. Plasticity of eukaryotic cell metabolism according to the environmental changes is ensured by adequate mitochondria functioning by means of ATP synthesis coordination, reactive oxygen species accumulation, apoptosis regulation and is an important factor of cell adaptation to stress. Mitochondria participation in important for cell vitality processes masters the presence of accurate mechanisms of mitochondria functions regulation according to environment fluctuations. The mechanisms of mitochondria division and distribution are highly conserved. Baker yeast S. cerevisiae is an ideal model object for mitochondria researches due to energetic metabolism lability, ability to switch over respiration to fermentation, and petite-positive phenotype. Correction of metabolism according to the environmental changes is necessary for cell vitality. The influence of respiratory, carbon, amino acid and phosphate metabolism on mitochondria functions was shown. As far as the mechanisms that stabilize functions of mitochondria and mtDNA are highly conserve, we can project yeast regularities on higher eukaryotes systems. This makes it possible to approximate understanding the etiology and pathogenesis of a great number of human diseases.

Comprehensive analysis of Arabidopsis expression level polymorphisms with simple inheritance

PubMed Central

Plantegenet, Stephanie; Weber, Johann; Goldstein, Darlene R; Zeller, Georg; Nussbaumer, Cindy; Thomas, Jérôme; Weigel, Detlef; Harshman, Keith; Hardtke, Christian S

2009-01-01

In Arabidopsis thaliana, gene expression level polymorphisms (ELPs) between natural accessions that exhibit simple, single locus inheritance are promising quantitative trait locus (QTL) candidates to explain phenotypic variability. It is assumed that such ELPs overwhelmingly represent regulatory element polymorphisms. However, comprehensive genome-wide analyses linking expression level, regulatory sequence and gene structure variation are missing, preventing definite verification of this assumption. Here, we analyzed ELPs observed between the Eil-0 and Lc-0 accessions. Compared with non-variable controls, 5′ regulatory sequence variation in the corresponding genes is indeed increased. However, ∼42% of all the ELP genes also carry major transcription unit deletions in one parent as revealed by genome tiling arrays, representing a >4-fold enrichment over controls. Within the subset of ELPs with simple inheritance, this proportion is even higher and deletions are generally more severe. Similar results were obtained from analyses of the Bay-0 and Sha accessions, using alternative technical approaches. Collectively, our results suggest that drastic structural changes are a major cause for ELPs with simple inheritance, corroborating experimentally observed indel preponderance in cloned Arabidopsis QTL. PMID:19225455

Radio-induced inherited sterility in Heliothis zea (Boddie)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, J.E.

1985-01-01

Heliothis zea (Boddie) (Lepidoptera: Noctuidae) males and females were irradiated with substerilizing doses of radiation. These moths were inbred and outcrossed and observed for their ability to reproduce. The inherited deleterious effects resulting from the irradiated P/sub 1/ males were recorded for several generations. Larvae from both irradiated (10 krad) and normal parents were compared for their ability to survive under field conditions on whole-stage sweet corn and these results were compared with those from a laboratory study using meridic diet. Irradiated males and females and F/sub 1/ males from an irradiated (10 krad) male x normal female cross weremore » released in the field and in field cages and observed for their ability to search/attract and secure a mate. Females that had mated with normal and irradiated (10 krad) males were studied to determine the effect of different mating histories on the subsequent mating propensity of the females. A 10-krad dose of radiation induced deleterious effects which were inherited through the F/sub 2/ generation. These radiation-induced deleterious effects were similar to those reported in other species of Lepidoptera. The relationship between the survival of normal larvae and larvae from irradiated parents was similar under laboratory and field rearing conditions. Females mated to normal males and males irradiated with 10 krad had the same mating propensity and experienced the same intermating interval. These effects of substerilizing doses of radiation and inherited sterility on the reproductive ability and behavior of H. zea suggest that a great potential exists for population suppression.« less

Experience inheritance from famous specialists based on real-world clinical research paradigm of traditional Chinese medicine.

PubMed

Song, Guanli; Wang, Yinghui; Zhang, Runshun; Liu, Baoyan; Zhou, Xuezhong; Zhou, Xiaji; Zhang, Hong; Guo, Yufeng; Xue, Yanxing; Xu, Lili

2014-09-01

The current modes of experience inheritance from famous specialists in traditional Chinese medicine (TCM) include master and disciple, literature review, clinical-epidemiology-based clinical research observation, and analysis and data mining via computer and database technologies. Each mode has its advantages and disadvantages. However, a scientific and instructive experience inheritance mode has not been developed. The advent of the big data era as well as the formation and practice accumulation of the TCM clinical research paradigm in the real world have provided new perspectives, techniques, and methods for inheriting experience from famous TCM specialists. Through continuous exploration and practice, the research group proposes the innovation research mode based on the real-world TCM clinical research paradigm, which involves the inheritance and innovation of the existing modes. This mode is formulated in line with its own development regularity of TCM and is expected to become the main mode of experience inheritance in the clinical field.

Inheritance of astigmatism: evidence for a major autosomal dominant locus.

PubMed Central

Clementi, M; Angi, M; Forabosco, P; Di Gianantonio, E; Tenconi, R

1998-01-01

Although astigmatism is a frequent refractive error, its mode of inheritance remains uncertain. Complex segregation analysis was performed, by the POINTER and COMDS programs, with data from a geographically well-defined sample of 125 nuclear families of individuals affected by astigmatism. POINTER could not distinguish between alternative genetic models, and only the hypothesis of no familial transmission could be rejected. After inclusion of the severity parameter, COMDS results defined a genetic model for corneal astigmatism and provided evidence for single-major-locus inheritance. These results suggest that genetic linkage studies could be implemented and that they should be limited to multiplex families with severely affected individuals. PMID:9718344

What Are They Thinking? The Development and Use of an Instrument that Identifies Common Science Misconceptions

ERIC Educational Resources Information Center

Stein, Mary; Barman, Charles R.; Larrabee, Timothy

2007-01-01

This article describes the rationale for, and development of, an online instrument that helps identify commonly held science misconceptions. Science Beliefs is a 47-item instrument that targets topics in chemistry, physics, biology, earth science, and astronomy. It utilizes a true or false, along with a written-explanation, format. The true or…

Comparative Genome-Wide-Association Mapping Identifies Common Loci Controlling Root System Architecture and Resistance to Aphanomyces euteiches in Pea.

PubMed

Desgroux, Aurore; Baudais, Valentin N; Aubert, Véronique; Le Roy, Gwenola; de Larambergue, Henri; Miteul, Henri; Aubert, Grégoire; Boutet, Gilles; Duc, Gérard; Baranger, Alain; Burstin, Judith; Manzanares-Dauleux, Maria; Pilet-Nayel, Marie-Laure; Bourion, Virginie

2017-01-01

additional intervals associated with plant architecture overlapped with GWA intervals previously identified for resistance to A. euteiches . This study provides innovative results about genetic interdependency of root disease resistance and RSA inheritance. It identifies pea lines, QTL, closely-linked markers and candidate genes for marker-assisted-selection of RSA loci to reduce Aphanomyces root rot severity in future pea varieties.

Comparative Genome-Wide-Association Mapping Identifies Common Loci Controlling Root System Architecture and Resistance to Aphanomyces euteiches in Pea

PubMed Central

Desgroux, Aurore; Baudais, Valentin N.; Aubert, Véronique; Le Roy, Gwenola; de Larambergue, Henri; Miteul, Henri; Aubert, Grégoire; Boutet, Gilles; Duc, Gérard; Baranger, Alain; Burstin, Judith; Manzanares-Dauleux, Maria; Pilet-Nayel, Marie-Laure; Bourion, Virginie

2018-01-01

intervals associated with plant architecture overlapped with GWA intervals previously identified for resistance to A. euteiches. This study provides innovative results about genetic interdependency of root disease resistance and RSA inheritance. It identifies pea lines, QTL, closely-linked markers and candidate genes for marker-assisted-selection of RSA loci to reduce Aphanomyces root rot severity in future pea varieties. PMID:29354146

Human and animal evidence of potential transgenerational inheritance of health effects: An evidence map and state-of-the-science evaluation.

PubMed

Walker, Vickie R; Boyles, Abee L; Pelch, Katherine E; Holmgren, Stephanie D; Shapiro, Andrew J; Blystone, Chad R; Devito, Michael J; Newbold, Retha R; Blain, Robyn; Hartman, Pamela; Thayer, Kristina A; Rooney, Andrew A

2018-06-01

An increasing number of reports suggest early life exposures result in adverse effects in offspring who were never directly exposed; this phenomenon is termed "transgenerational inheritance." Given concern for public health implications for potential effects of exposures transmitted to subsequent generations, it is critical to determine how widespread and robust this phenomenon is and to identify the range of exposures and possible outcomes. This scoping report examines the evidence for transgenerational inheritance associated with exposure to a wide range of stressors in humans and animals to identify areas of consistency, uncertainty, data gaps, and to evaluate general risk of bias issues for the transgenerational study design. A protocol was developed to collect and categorize the literature into a systematic evidence map for transgenerational inheritance by health effects, exposures, and evidence streams following the Office of Health Assessment and Translation (OHAT) approach for conducting literature-based health assessments. A PubMed search yielded 63,758 unique records from which 257 relevant studies were identified and categorized into a systematic evidence map by evidence streams (46 human and 211 animal), broad health effect categories, and exposures. Data extracted from the individual studies are available in the Health Assessment Workspace Collaborative (HAWC) program. There are relatively few bodies of evidence where multiple studies evaluated the same exposure and the same or similar outcomes. Studies evaluated for risk of bias generally had multiple issues in design or conduct. The evidence mapping illustrated that risk of bias, few studies, and heterogeneity in exposures and endpoints examined present serious limitations to available bodies of evidence for assessing transgenerational effects. Targeted research is suggested to addressed inconsistencies and risk of bias issues identified, and thereby establish more robust bodies of evidence to

Identifying Common Practice Elements to Improve Social, Emotional, and Behavioral Outcomes of Young Children in Early Childhood Classrooms.

PubMed

McLeod, Bryce D; Sutherland, Kevin S; Martinez, Ruben G; Conroy, Maureen A; Snyder, Patricia A; Southam-Gerow, Michael A

2017-02-01

Educators are increasingly being encouraged to implement evidence-based interventions and practices to address the social, emotional, and behavioral needs of young children who exhibit problem behavior in early childhood settings. Given the nature of social-emotional learning during the early childhood years and the lack of a common set of core evidence-based practices within the early childhood literature, selection of instructional practices that foster positive social, emotional, and behavioral outcomes for children in early childhood settings can be difficult. The purpose of this paper is to report findings from a study designed to identify common practice elements found in comprehensive intervention models (i.e., manualized interventions that include a number of components) or discrete practices (i.e., a specific behavior or action) designed to target social, emotional, and behavioral learning of young children who exhibit problem behavior. We conducted a systematic review of early childhood classroom interventions that had been evaluated in randomized group designs, quasi-experimental designs, and single-case experimental designs. A total of 49 published articles were identified, and an iterative process was used to identify common practice elements. The practice elements were subsequently reviewed by experts in social-emotional and behavioral interventions for young children. Twenty-four practice elements were identified and classified into content (the goal or general principle that guides a practice element) and delivery (the way in which a teacher provides instruction to the child) categories. We discuss implications that the identification of these practice elements found in the early childhood literature has for efforts to implement models and practices.

RAPD inheritance and diversity in pawpaw (Asimina triloba)

Treesearch

Hongwen Huang; Desmond R. Layne; Thomas L. Kubisiak

2000-01-01

Twelve, 10-base primers amplified a total of 20 intense and easily scorable polymorphic bands in an interspecific cross of PPFl-5 pawpaw (Asimina triloba (L.) Dunal.) x RET (Asimina reticulata Shuttlew.). In this cross, all bands scored were present in, and inherited from, the A. triloba ...

Dominantly inherited syndrome of microcephaly and cleft palate.

PubMed

Halal, F

1983-05-01

Two sisters and their mother had a syndrome of microcephaly, cleft palate, and variable anomalies such as unusual facial appearance, hypotelorism, abnormal retinal pigmentation, maxillary hypoplasia, goiter, camptodactyly, mild mental retardation, and abnormal dermatoglyphics. This is an evidently dominantly inherited trait, either autosomal or X-linked.

Impacts of salt marsh plants on tidal channel initiation and inheritance

NASA Astrophysics Data System (ADS)

Schwarz, Christian; Ye, Qinghua; van der Wal, Daphne; Zhang, Liquan; Ysebaert, Tom; Herman, Peter MJ

2013-04-01

Tidal channel networks are the most prominent and striking features visible in tidal wetlands. They serve as major pathways for the exchange of water, sediments, nutrients and contaminants between the wetland and the adjacent open water body. Previous studies identified topography guided sheet flows, as the predominate process for tidal channel initiation. Guided through differences in local topography, sheet flows are able to locally exceed bottom shear stress thresholds, initiating scouring and incision of tidal channels, which then further grow through head ward erosion. The fate of these channels after plant colonization is described in literature as being inherited into the salt marsh through vegetation induced bank stabilization (further referred to as vegetation stabilized channel inheritance). In this study we present a combination of flume experiments and modelling simulations elucidating the impact of vegetation on tidal channel initiation. We first studied the impact of plant properties (stiff: Spartina alterniflora versus flexible: Scirpus mariqueter) on local sediment transport utilizing a flume experiment. Then a coupled hydrodynamic morphodynamic plant growth model was set up to simulate plant colonization by these two different species in the pioneer zone at the mudflat - salt marsh transition. Based on the model we investigated the ramifications of interactions between vegetation, sediment and flow on tidal channel initiation. We specifically compared the effect of vegetation properties (such as stiffness, growth velocity and stress tolerance) on emerging channel patterns, hypothesizing that vegetation mediated channel incision (vegetation induced flow routing and differential sedimentation/erosion patterns leading to tidal channel incision) plays an active role in intertidal landscape evolution. We finally extended our model simulation by imposing pre-existing mudflat channels with different maximum depths, to investigate the impact of existing

Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

PubMed Central

Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K.

2013-01-01

Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures. PMID:23359474

From rifting to subduction: the role of inheritance in the Wilson Cycle

NASA Astrophysics Data System (ADS)

Beaussier, Stéphane; Gerya, Taras; Burg, Jean-Pierre

2017-04-01

The Wilson Cycle entails that oceans close and reopen. This cycle is a fundamental principle in plate tectonics, inferring continuity from divergence to convergence and that continental rifting takes place along former suture zones. This view questions the role of inherited structures at each stage of the Wilson Cycle. Using the 3D thermo-mechanical code, I3ELVIS (Gerya and Yuen 2007) we present a high-resolution continuous model of the Wilson cycle from continental rifting, breakup and oceanic spreading to convergence and spontaneous subduction initiation. Therefore, all lateral and longitudinal structures of the lithospheres are generated self-consistently and are consequences of the initial continental structure, tectono-magmatic inheritance and material rheology. In the models, subduction systematically initiates off-ridge and is controlled by the convergence-induced swelling of the ridge. Geometry and dynamics of the developing off-ridge subduction is controlled by four main factors: (1) the obliquity of the ridge with respect to the convergence direction; (2) fluid-induced weakening of the oceanic crust; (3) irregularity of ridge and margins inherited from rifting and spreading; (4) strain localization at transform faults formed during ocean floor spreading. Further convergence can lead to obduction of the oceanic crust and segments of ridge after the oceanic lithosphere is entrained into subduction. We show that the main parameters controlling the occurrence and geometry of obducted ophiolite are the convergence rate and the inherited structure of the passive margins and ridge. Our numerical experiments results show the essential role played by inheritance during the Wilson Cycle and are consistent with nature observations such as the tectonic history of the Oman subduction-obduction system. REFERENCES Gerya, T. V., and D. A. Yuen. 2007: "Robust Characteristics Method for Modelling Multiphase Visco-Elasto-Plastic Thermo-Mechanical Problems, Physics of the

[Study on the mode of inheritance for familial polycystic ovary syndrome].

PubMed

Mao, W; Li, M; Chen, Y; Lu, C; Wang, Y; Zhang, X; Qiao, J; Wang, A

2001-02-01

To investigate the mode of inheritance of polycystic ovary syndrome(PCOS). The first female relatives with irregular cycle and the first male relatives with premature balding in each nuclear family were designated the affected. Their prevalence rates in families were respectively calculated. Analyses of segregation ratio were carried out among 139 nuclear families with PCOS by the methods of simple segregation and complex segregation of genetic epidemiology, respectively. The prevalence rates of irregular cycle among mothers and sisters with PCOS were 37.4% and 33.1% respectively, and the prevalence rates of premature balding among fathers and brothers of patients were 19.4% and 6.5%, respectively. The simple segregation analysis indicated that the segregation ratio of PCOS trait in siblings was 0.3023, the complex segregation analysis indicated that it fitted in with the inheritance model of co-dominant disorder with full penetrance and sporadic cases. The frequency of homozygote of disease gene in population was 0.046. PCOS presents the mode of co-dominant inheritance with complete penetrance.

Understanding of and attitudes to genetic testing for inherited retinal disease: a patient perspective.

PubMed

Willis, T A; Potrata, B; Ahmed, M; Hewison, J; Gale, R; Downey, L; McKibbin, M

2013-09-01

The views of people with inherited retinal disease are important to help develop health policy and plan services. This study aimed to record levels of understanding of and attitudes to genetic testing for inherited retinal disease, and views on the availability of testing. Telephone questionnaires comprising quantitative and qualitative items were completed with adults with inherited retinal disease. Participants were recruited via postal invitation (response rate 48%), approach at clinic or newsletters of relevant charitable organisations. Questionnaires were completed with 200 participants. Responses indicated that participants' perceived understanding of genetic testing for inherited retinal disease was variable. The majority (90%) considered testing to be good/very good and would be likely to undergo genetic testing (90%) if offered. Most supported the provision of diagnostic (97%) and predictive (92%) testing, but support was less strong for testing as part of reproductive planning. Most (87%) agreed with the statement that testing should be offered only after the individual has received genetic counselling from a professional. Subgroup analyses revealed differences associated with participant age, gender, education level and ethnicity (p<0.02). Participants reported a range of perceived benefits (eg, family planning, access to treatment) and risks (eg, impact upon family relationships, emotional consequences). Adults with inherited retinal disease strongly support the provision of publicly funded genetic testing. Support was stronger for diagnostic and predictive testing than for testing as part of reproductive planning.

Hematological parameters and red blood cell morphological abnormality of Glucose-6-Phosphate dehydrogenase deficiency co-inherited with thalassemia.

PubMed

Pengon, Jutharat; Svasti, Saovaros; Kamchonwongpaisan, Sumalee; Vattanaviboon, Phantip

2018-03-01

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and thalassemia are genetically independent hemolytic disorders. Co-inheritance of both disorders may affect red blood cell pathology to a greater extent than normally seen in either disorder alone. This study determines the prevalence and evaluates hematological changes of G-6-PD deficiency and thalassemia co-inheritance. G-6-PD deficiency was screened from 200 male thalassemia blood samples using a fluorescent spot test. Hematological parameters and red blood cell morphology were evaluated among G-6-PD deficiency/thalassemia co-inheritance, G-6-PD deficiency alone, thalassemia alone, and normal individuals. G-6-PD deficiency was detected together with hemoglobin (Hb) E heterozygote, Hb E homozygote, β-thalassemia trait, and β-thalassemia/Hb E, α-thalassemia-2 trait, and Hb H disease. Hb level, hematocrit, mean cell volume, and mean cell Hb of G-6-PD deficiency co-inherited with asymptomatic thalassemia carriers show significantly lower mean values compared to carriers with only the same thalassemia genotypes. Higher mean red blood cell distribution width was observed in G-6-PD deficiency co-inherited with Hb E heterozygote, as with numbers of hemighost cells in G-6-PD deficiency/thalassemia co-inheritance compared to those with either disorder. Apart from Hb level, hematological parameters of co-inheritance disorders were not different from individuals with a single thalassemia disease. G-6-PD deficiency co-inherited with thalassemia in males was present in 10% of the participants, resulting in worsening of red blood cell pathology compared with inheritance of thalassemia alone. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Inherited hypothyroidism.

PubMed

Jackson, I M

1976-03-01

Familial hypothyroidism results from both thyroidal and extrathyroidal dysfunction. Specific intrathyroidal abnormalities in thyroid hormone synthesis causing goitrous hypothyroidism are iodide trap defect, organification defect, "coupling" defect, iodoprotein defect, and dehalogenase defect. The diagnostic studies for each are outlined utilizing radioiodine(131I) studies. Other causes of cretinism include failure of the thyroid gland to respond to TSH and lack of pituitary TSH (or hypothalamic TRH). The syndrome of peripheral resistance to thyroid hormone is discussed. The diagnosis of inherited hypothyrodism rests on an adequate family history and measurement of both T4 and TSH levels which can be determined in cord blood or peripheral blood from the infant. The importance of early treatment of hypothyroidism in the neonatal period to prevent brain damage is emphasized. The rec:nt discovery of the importance of reverse T3 (RT3) in fetal thyroid metabolism is described, and the possibility of amniocentesis as an aid in prenatal diagnosis is considered. The place of intrauterine administration of thyroid hormone to the fetus at risk from hypothyroidism is uncertain at this time and requires carefully controlled studies and long-term follow-up.

Sexual Reproduction in Aspergillus flavus Sclerotia: Acquisition of Novel Alleles from Soil Populations and Uniparental Mitochondrial Inheritance

PubMed Central

Horn, Bruce W.; Gell, Richard M.; Singh, Rakhi; Sorensen, Ronald B.; Carbone, Ignazio

2016-01-01

Aspergillus flavus colonizes agricultural commodities worldwide and contaminates them with carcinogenic aflatoxins. The high genetic diversity of A. flavus populations is largely due to sexual reproduction characterized by the formation of ascospore-bearing ascocarps embedded within sclerotia. A. flavus is heterothallic and laboratory crosses between strains of the opposite mating type produce progeny showing genetic recombination. Sclerotia formed in crops are dispersed onto the soil surface at harvest and are predominantly produced by single strains of one mating type. Less commonly, sclerotia may be fertilized during co-infection of crops with sexually compatible strains. In this study, laboratory and field experiments were performed to examine sexual reproduction in single-strain and fertilized sclerotia following exposure of sclerotia to natural fungal populations in soil. Female and male roles and mitochondrial inheritance in A. flavus were also examined through reciprocal crosses between sclerotia and conidia. Single-strain sclerotia produced ascospores on soil and progeny showed biparental inheritance that included novel alleles originating from fertilization by native soil strains. Sclerotia fertilized in the laboratory and applied to soil before ascocarp formation also produced ascospores with evidence of recombination in progeny, but only known parental alleles were detected. In reciprocal crosses, sclerotia and conidia from both strains functioned as female and male, respectively, indicating A. flavus is hermaphroditic, although the degree of fertility depended upon the parental sources of sclerotia and conidia. All progeny showed maternal inheritance of mitochondria from the sclerotia. Compared to A. flavus populations in crops, soil populations would provide a higher likelihood of exposure of sclerotia to sexually compatible strains and a more diverse source of genetic material for outcrossing. PMID:26731416

A two-step process for epigenetic inheritance in Arabidopsis

PubMed Central

Blevins, Todd; Pontvianne, Frédéric; Cocklin, Ross; Podicheti, Ram; Chandrasekhara, Chinmayi; Yerneni, Satwica; Braun, Chris; Lee, Brandon; Rusch, Doug; Mockaitis, Keithanne; Tang, Haixu; Pikaard, Craig S.

2014-01-01

Summary In Arabidopsis, multisubunit RNA polymerases IV and V orchestrate RNA-directed DNA methylation (RdDM) and transcriptional silencing, but what identifies the loci to be silenced is unclear. We show that heritable silent locus identity at a specific subset of RdDM targets requires HISTONE DEACETYLASE 6 (HDA6) acting upstream of Pol IV recruitment and siRNA biogenesis. At these loci, epigenetic memory conferring silent locus identity is erased in hda6 mutants such that restoration of HDA6 activity cannot restore siRNA biogenesis or silencing. Silent locus identity is similarly lost in mutants for the cytosine maintenance methyltransferase, MET1. By contrast, pol IV or pol V mutants disrupt silencing without erasing silent locus identity, allowing restoration of Pol IV or Pol V function to restore silencing. Collectively, these observations indicate that silent locus specification and silencing are separable steps that together account for epigenetic inheritance of the silenced state. PMID:24657166

Inherited selective intestinal cobalamin malabsorption and cobalamin deficiency in dogs.

PubMed

Fyfe, J C; Giger, U; Hall, C A; Jezyk, P F; Klumpp, S A; Levine, J S; Patterson, D F

1991-01-01

Inherited selective intestinal malabsorption of cobalamin (Cbl) was observed in a family of giant schnauzer dogs. Family studies and breeding experiments demonstrated simple autosomal recessive inheritance of this disease. Affected puppies exhibited chronic inappetence and failure to thrive beginning between 6 and 12 wk of age. Neutropenia with hypersegmentation, anemia with anisocytosis and poikilocytosis, and megaloblastic changes of the bone marrow were present. Serum Cbl concentrations were low, and methylmalonic aciduria and homocysteinemia were present. Parenteral, but not oral, cyanocobalamin administration rapidly eliminated all signs of Cbl deficiency except for low serum Cbl concentrations. Cbl malabsorption in affected dogs was documented by oral administration of [57Co]cyanocobalamin with or without simultaneous oral administration of intrinsic factor or normal dog gastric juice. Quantitation and function studies of intrinsic factor and transcobalamin-II from affected dogs revealed no abnormality. Other gastrointestinal functions and ileal morphology were normal, indicating a selective defect of Cbl absorption at the level of the ileal enterocyte. Immunoelectron microscopy of ileal biopsies showed that the receptor for intrinsic factor-Cbl complex was absent from the apical brush border microvillus pits of affected dogs. This canine disorder resembles inherited selective intestinal Cbl malabsorption (Imerslund-Gräsbeck syndrome) in humans, and is a spontaneously occurring animal model of early onset Cbl deficiency.

Storage proteins of common bean identified with 2D-PAGE

USDA-ARS?s Scientific Manuscript database

The common bean is a significant source of protein, complex carbohydrates, fiber, and minerals. Seeds of most dry beans contain 15 to 25% protein and are rich in lysine but low in the sulfur containing amino acids cysteine and methionine. Knowledge of common bean proteins is important for research a...

Maternal inheritance of the chloroplast genome in Eucalyptus globulus and interspecific hybrids.

PubMed

Mckinnon, A E; Vaillancourt, R E; Tilyard, P A; Potts, B M

2001-10-01

The utility of chloroplast DNA (cpDNA) in Eucalyptus, either as a molecular marker for genetic studies or as a potential vehicle for genetic manipulation, is based on knowledge of its mode of inheritance. Chloroplast inheritance in angiosperms can vary among and within species, and anomalous inheritance has been reported in some interspecific-hybrid combinations. In Eucalyptus, abnormalities of pollen-tube growth occur in a number of interspecific-hybrid combinations, and this might increase the likelihood of anomalous chloroplast transmission. We used a rapid PCR technique to determine chloroplast heritability in 425 progeny of Eucalyptus, comprising 194 progeny of the premier pulpwood species E. globulus and 231 interspecific hybrids between E. globulus and E. nitens (F1, F2, and backcrosses). At this sampling intensity, no pollen-mediated transmission of cpDNA was found in any of the 40 families tested. The results are discussed with reference to chloroplast engineering and the use of cpDNA as a seed-specific marker in phylogeographic studies of Eucalyptus.

[Analysis on composition principles of prescriptions for nausea by using traditional Chinese medicine inheritance support system].

PubMed

Han, Qi; Li, Hong-Hai; Fan, Cui-Ping; Liu, Chun; Liang, Yong-Lin

2016-07-01

Nausea is special in the symptoms, and is different from hiccups and vomiting. The main symptom is that the patients throw up the indigested food from the stomach regularly--if the patients have a dinner, they will throw out it in the next morning, or if the patients have a breakfast, they will throw out it at night. Nausea is common in clinic, and different physicians may use different treatment methods for it. This disease also cannot be treated efficiently and may happen repeatedly with the western medicine. In this study, the composition principles of prescriptions in past traditional Chinese medicine for nausea were analyzed and summarized by using traditional Chinese medicine inheritance support system(V2.5), hoping to provide guidance for clinical drug use and summarize the basic rules for treatment of nausea.The prescriptions for nausea in "the prescription of traditional Chinese medicine dictionary" were selected, and the information was entered into the traditional Chinese medicine inheritance support system(TCMISS) to build a database. Data mining methods such as frequency statistics, association rules, complex system entropy clustering were used to analyze and summarize the composition principles of these prescriptions. The herb frequencies of the prescriptions were finally determined; herbs with higher use frequencies were obtained; and the association rules between herbs were found. 19 commonly used herb pairs, 10 core combinations and 10 newly developed prescriptions were found. The basic pathogenesis of nausea in traditional Chinese medicine is the weakness and coldness of spleen and stomach, and the Qi adverseness of stomach. Generations of physicians' main therapeutic method for nausea is mainly to warm the middle and invigorate the spleen, lower Qi and regulate stomach. The commonly used herbs for nausea are ginger, ginseng, large head attractylodes, tuckahoe, licorice, and appropriately supplemented with the herbs of eliminating dampness and

Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

PubMed

Yu-Wai-Man, Patrick

2016-10-01

Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Obstetric bleeding among women with inherited bleeding disorders: a retrospective study.

PubMed

Hawke, L; Grabell, J; Sim, W; Thibeault, L; Muir, E; Hopman, W; Smith, G; James, P

2016-11-01

Women with inherited bleeding disorders are at increased risk for bleeding complications during pregnancy and the postpartum period, particularly postpartum haemorrhage (PPH). This retrospective study evaluates pregnancy management through the Inherited Bleeding Disorders Clinic of Southeastern Ontario, the clinical factors associated with pregnancy-related abnormal bleeding and assesses tranexamic acid use in the postpartum treatment of bleeding disorder patients. A chart review of 62 pregnancies, from 33 women, evaluated patient characteristics (age, haemostatic factor levels) and delivery conditions (mode of delivery, postpartum treatment) in relation to abnormal postpartum bleeding. This cohort revealed increased risk of immediate PPH with increased age at delivery (mean age: 30.1 years with PPH, 26.5 years without PPH, P < 0.013), and birth by vaginal delivery (P < 0.042). Low von Willebrand factor (VWF) antigen or factor VIII (FVIII) in the third trimester was not associated with an increased risk of PPH; however, low VWF:RCo was associated with increased immediate PPH despite treatment with continuous factor infusion (P < 0.042). Women treated with tranexamic acid postpartum had less severe bleeding in the 6-week postpartum (P < 0.049) with no thrombotic complications. This study contributes to the growing body of work aimed at optimizing management of bleeding disorder patients through pregnancy and the postpartum period, showing patients are at a higher risk of PPH as they age. Risk factors such as low third trimester VWF:RCo have been identified. Treatment with tranexamic acid in the postpartum period is associated with a reduced incidence of abnormal postpartum bleeding. © 2016 John Wiley & Sons Ltd.

Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis

PubMed Central

Barbaro, Michela; Cook, Jackie; Lagerstedt-Robinson, Kristina; Wedell, Anna

2012-01-01

A 160 kb minimal common region in Xp21 has been determined as the cause of XY gonadal dysgenesis, if duplicated. The region contains the MAGEB genes and the NR0B1 gene; this is the candidate for gonadal dysgenesis if overexpressed. Most patients present gonadal dysgenesis within a more complex phenotype. However, few independent cases have recently been described presenting with isolated XY gonadal dysgenesis caused by relatively small NR0B1 locus duplications. We have identified another NR0B1 duplication in two sisters with isolated XY gonadal dysgenesis with an X-linked inheritance pattern. We performed X-inactivation studies in three fertile female carriers of three different small NR0B1 locus duplications identified by our group. The carrier mothers did not show obvious skewing of X-chromosome inactivation, suggesting that NR0B1 overexpression does not impair ovarian function. We furthermore emphasize the importance to investigate the NR0B1 locus also in patients with isolated XY gonadal dysgenesis. PMID:22518125

Understanding of and attitudes to genetic testing for inherited retinal disease: a patient perspective

PubMed Central

Willis, T A; Potrata, B; Ahmed, M; Hewison, J; Gale, R; Downey, L; McKibbin, M

2013-01-01

Background/aims The views of people with inherited retinal disease are important to help develop health policy and plan services. This study aimed to record levels of understanding of and attitudes to genetic testing for inherited retinal disease, and views on the availability of testing. Methods Telephone questionnaires comprising quantitative and qualitative items were completed with adults with inherited retinal disease. Participants were recruited via postal invitation (response rate 48%), approach at clinic or newsletters of relevant charitable organisations. Results Questionnaires were completed with 200 participants. Responses indicated that participants’ perceived understanding of genetic testing for inherited retinal disease was variable. The majority (90%) considered testing to be good/very good and would be likely to undergo genetic testing (90%) if offered. Most supported the provision of diagnostic (97%) and predictive (92%) testing, but support was less strong for testing as part of reproductive planning. Most (87%) agreed with the statement that testing should be offered only after the individual has received genetic counselling from a professional. Subgroup analyses revealed differences associated with participant age, gender, education level and ethnicity (p<0.02). Participants reported a range of perceived benefits (eg, family planning, access to treatment) and risks (eg, impact upon family relationships, emotional consequences). Conclusions Adults with inherited retinal disease strongly support the provision of publicly funded genetic testing. Support was stronger for diagnostic and predictive testing than for testing as part of reproductive planning. PMID:23813418

A test of the transcription model for biased inheritance of yeast mitochondrial DNA.

PubMed

Lorimer, H E; Brewer, B J; Fangman, W L

1995-09-01

Two strand-specific origins of replication appear to be required for mammalian mitochondrial DNA (mtDNA) replication. Structural equivalents of these origins are found in the rep sequences of Saccharomyces cerevisiae mtDNA. These striking similarities have contributed to a universal model for the initiation of mtDNA replication in which a primer is created by cleavage of an origin region transcript. Consistent with this model are the properties of deletion mutants of yeast mtDNA ([rho-]) with a high density of reps (HS [rho-]). These mutant mtDNAs are preferentially inherited by the progeny resulting from the mating of HS [rho-] cells with cells containing wild-type mtDNA ([rho+]). This bias is presumed to result from a replication advantage conferred on HS [rho-] mtDNA by the high density of rep sequences acting as origins. To test whether transcription is indeed required for the preferential inheritance of HS [rho-] mtDNA, we deleted the nuclear gene (RPO41) for the mitochondrial RNA polymerase, reducing transcripts by at least 1000-fold. Since [rho-] genomes, but not [rho+] genomes, are stable when RPO41 is deleted, we examined matings between HS [rho-] and neutral [rho-] cells. Neutral [rho-] mtDNAs lack rep sequences and are not preferentially inherited in [rho-] x [rho+] crosses. In HS [rho-] x neutral [rho-] matings, the HS [rho-] mtDNA was preferentially inherited whether both parents were wild type or both were deleted for RPO41. Thus, transcription from the rep promoter does not appear to be necessary for biased inheritance. Our results, and analysis of the literature, suggest that priming by transcription is not a universal mechanism for mtDNA replication initiation.

Epigenetic Inheritance and Its Role in Evolutionary Biology: Re-Evaluation and New Perspectives

PubMed Central

Burggren, Warren

2016-01-01

Epigenetics increasingly occupies a pivotal position in our understanding of inheritance, natural selection and, perhaps, even evolution. A survey of the PubMed database, however, reveals that the great majority (>93%) of epigenetic papers have an intra-, rather than an inter-generational focus, primarily on mechanisms and disease. Approximately ~1% of epigenetic papers even mention the nexus of epigenetics, natural selection and evolution. Yet, when environments are dynamic (e.g., climate change effects), there may be an “epigenetic advantage” to phenotypic switching by epigenetic inheritance, rather than by gene mutation. An epigenetically-inherited trait can arise simultaneously in many individuals, as opposed to a single individual with a gene mutation. Moreover, a transient epigenetically-modified phenotype can be quickly “sunsetted”, with individuals reverting to the original phenotype. Thus, epigenetic phenotype switching is dynamic and temporary and can help bridge periods of environmental stress. Epigenetic inheritance likely contributes to evolution both directly and indirectly. While there is as yet incomplete evidence of direct permanent incorporation of a complex epigenetic phenotype into the genome, doubtlessly, the presence of epigenetic markers and the phenotypes they create (which may sort quite separately from the genotype within a population) will influence natural selection and, so, drive the collective genotype of a population. PMID:27231949

Identifying common pressure pathways from a complex network of human activities to support ecosystem-based management.

PubMed

Knights, Antony M; Koss, Rebecca S; Robinson, Leonie A

2013-06-01

The marine environment is heavily exploited, but unintentional consequences cause wide-ranging negative effects to its characteristics. Linkage frameworks (e.g., DPSIR [driver-pressure-state-impact-response]) are commonly used to describe an interaction between human activities and ecological characteristics of the ecosystem, but as each linkage is viewed independently, the diversity of pressures that affect those characteristics may not be identified or managed effectively. Here we demonstrate an approach for using linkages to build a simple network to capture the complex relationships arising from multiple sectors and their activities. Using data-analysis tools common to ecology, we show how linkages can be placed into mechanistically similar groups. Management measures can be combined into fewer and more simplified measures that target groups of pressures rather than individual pressures, which is likely to increase compliance and the success of the measure while reducing the cost of enforcement. Given that conservation objectives (regional priorities) can vary, we also demonstrate by way of a case study example from the Marine Strategy Framework Directive, how management priorities might change, and illustrate how the approach can be used to identify sectors for control that best support the conservation objectives.

Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin.

PubMed

Ogrodnik, Mikołaj; Salmonowicz, Hanna; Brown, Rachel; Turkowska, Joanna; Średniawa, Władysław; Pattabiraman, Sundararaghavan; Amen, Triana; Abraham, Ayelet-chen; Eichler, Noam; Lyakhovetsky, Roman; Kaganovich, Daniel

2014-06-03

Aging is associated with the accumulation of several types of damage: in particular, damage to the proteome. Recent work points to a conserved replicative rejuvenation mechanism that works by preventing the inheritance of damaged and misfolded proteins by specific cells during division. Asymmetric inheritance of misfolded and aggregated proteins has been shown in bacteria and yeast, but relatively little evidence exists for a similar mechanism in mammalian cells. Here, we demonstrate, using long-term 4D imaging, that the vimentin intermediate filament establishes mitotic polarity in mammalian cell lines and mediates the asymmetric partitioning of damaged proteins. We show that mammalian JUNQ inclusion bodies containing soluble misfolded proteins are inherited asymmetrically, similarly to JUNQ quality-control inclusions observed in yeast. Mammalian IPOD-like inclusion bodies, meanwhile, are not always inherited by the same cell as the JUNQ. Our study suggests that the mammalian cytoskeleton and intermediate filaments provide the physical scaffold for asymmetric inheritance of dynamic quality-control JUNQ inclusions. Mammalian IPOD inclusions containing amyloidogenic proteins are not partitioned as effectively during mitosis as their counterparts in yeast. These findings provide a valuable mechanistic basis for studying the process of asymmetric inheritance in mammalian cells, including cells potentially undergoing polar divisions, such as differentiating stem cells and cancer cells.

Inheritance rules for Hierarchical Metadata Based on ISO 19115

NASA Astrophysics Data System (ADS)

Zabala, A.; Masó, J.; Pons, X.

2012-04-01

Mainly, ISO19115 has been used to describe metadata for datasets and services. Furthermore, ISO19115 standard (as well as the new draft ISO19115-1) includes a conceptual model that allows to describe metadata at different levels of granularity structured in hierarchical levels, both in aggregated resources such as particularly series, datasets, and also in more disaggregated resources such as types of entities (feature type), types of attributes (attribute type), entities (feature instances) and attributes (attribute instances). In theory, to apply a complete metadata structure to all hierarchical levels of metadata, from the whole series to an individual feature attributes, is possible, but to store all metadata at all levels is completely impractical. An inheritance mechanism is needed to store each metadata and quality information at the optimum hierarchical level and to allow an ease and efficient documentation of metadata in both an Earth observation scenario such as a multi-satellite mission multiband imagery, as well as in a complex vector topographical map that includes several feature types separated in layers (e.g. administrative limits, contour lines, edification polygons, road lines, etc). Moreover, and due to the traditional split of maps in tiles due to map handling at detailed scales or due to the satellite characteristics, each of the previous thematic layers (e.g. 1:5000 roads for a country) or band (Landsat-5 TM cover of the Earth) are tiled on several parts (sheets or scenes respectively). According to hierarchy in ISO 19115, the definition of general metadata can be supplemented by spatially specific metadata that, when required, either inherits or overrides the general case (G.1.3). Annex H of this standard states that only metadata exceptions are defined at lower levels, so it is not necessary to generate the full registry of metadata for each level but to link particular values to the general value that they inherit. Conceptually the metadata

Arm-Gal4 inheritance influences development and lifespan in Drosophila melanogaster.

PubMed

Slade, F A; Staveley, B E

2015-10-19

The UAS-Gal4 ectopic expression system is a widely used and highly valued tool that allows specific gene expression in Drosophila melanogaster. Yeast transcription factor Gal4 can be directed using D. melanogaster transcriptional control elements, and is often assumed to have little effect on the organism. By evaluation of the consequences of maternal and paternal inheritance of a Gal4 transgene under the transcriptional regulation of armadillo control elements (arm-Gal4), we demonstrated that Gal4 expression could be detrimental to development and longevity. Male progeny expressing arm-Gal4 in the presence of UAS-lacZ transgene had reduced numbers and size of ommatidia, compared to flies expressing UAS-lacZ transgene under the control of other Gal4 transgenes. Aged at 25°C, the median life span of male flies with maternally inherited elav-Gal4 was 70 days, without a responding transgene or with UAS-lacZ. The median life span of maternally inherited arm-Gal4 male flies without a responding transgene was 48 days, and 40 days with the UAS-lacZ transgene. A partial rescue of this phenotype was observed with the expression of UAS-lacZ under paternal arm-Gal4 control, having an average median lifespan of 60 days. This data suggests that arm-Gal4 has detrimental effects on Drosophila development and lifespan that are directly dependent upon parental inheritance, and that the benign responder and reporter gene UAS-lacZ may influence D. melanogaster development. These findings should be taken into consideration during the design and execution of UAS-Gal4 expression experiments.

Inherited retinal dysplasia and persistent hyperplastic primary vitreous in Miniature Schnauzer dogs.

PubMed

Grahn, Bruce H; Storey, Eric S; McMillan, Catherine

2004-01-01

The objectives of this study were to define the clinical syndrome of retinal dysplasia and persistent primary vitreous in Miniature Schnauzer dogs and determine the etiology. We examined 106 Miniature Schnauzers using a biomicroscope and indirect ophthalmoscope. The anterior and posterior segments of affected dogs were photographed. Four enucleated eyes were examined using routine light microscopy and scanning electron microscopy. A pedigree was constructed and related dogs were test-bred to define the mode of inheritance of this syndrome. Congenital retinal dysplasia was confirmed in 24 of 106 related Miniature Schnauzer dogs. Physical and postmortem examinations revealed that congenital abnormalities were limited to the eyes. Biomicroscopic, indirect ophthalmoscopic, and neuro-ophthalmic examinations confirmed that some of these dogs were blind secondary to bilateral retinal dysplasia and detachment (nonattachment) (n = 13), and the remainder had generalized retinal dysplasia (n = 11). Fifteen of these dogs were also diagnosed with unilateral (n = 9) or bilateral (n = 6) persistent hyperplastic primary vitreous. Nutritional, infectious, or toxic etiologies were not evident on physical, postmortem, light microscopic, or transmitting and scanning electron microscopic examination of four affected Miniature Schnauzers. We examined the pedigree and determined that an autosomal recessive mode of inheritance was most likely. Three test-bred litters including those from affected parents, carrier and affected parents, and carrier parents confirmed this mode of inheritance. This study confirms that retinal dysplasia and persistent hyperplastic primary vitreous is a congenital abnormality that is inherited as an autosomal recessive condition in Miniature Schnauzers.

Beyond classical inheritance: the influence of maternal genotype upon child's brain morphology and behavior.

PubMed

van der Knaap, Noortje J F; El Marroun, Hanan; Klumpers, Floris; Mous, Sabine E; Jaddoe, Vincent W V; Hofman, Albert; Homberg, Judith R; White, Tonya; Tiemeier, Henning; Fernández, Guillén

2014-07-16

Genetic variance has been associated with variations in brain morphology, cognition, behavior, and disease risk. One well studied example of how common genetic variance is associated with brain morphology is the serotonin transporter gene polymorphism within the promoter region (5-HTTLPR). Because serotonin is a key neurotrophic factor during brain development, genetically determined variations in serotonin activity during maturation, in particular during early prenatal development, may underlie the observed association. However, the intrauterine microenvironment is not only determined by the child's, but also the mother's genotype. Therefore, we hypothesized that maternal 5-HTTLPR genotype influences the child's brain development beyond direct inheritance. To test this hypothesis, we investigated 76 children who were all heterozygous for the 5-HTTLPR (sl) and who had mothers who were either homozygous for the long (ll) or the short allele (ss). Using MRI, we assessed brain morphology as a function of maternal genotype. Gray matter density of the somatosensory cortex was found to be greater in children of ss mothers compared with children of ll mothers. Behavioral assessment showed that fine motor task performance was altered in children of ll mothers and the degree of this behavioral effect correlated with somatosensory cortex density across individuals. Our findings provide initial evidence that maternal genotype can affect the child's phenotype beyond effects of classical inheritance. Our observation appears to be explained by intrauterine environmental differences or by differences in maternal behavior. Copyright © 2014 the authors 0270-6474/14/349516-06$15.00/0.

Identification of a novel inherited ALK variant M1199L in the WNT type of medulloblastoma.

PubMed

Trubicka, J; Szperl, M; Grajkowska, W; Karkucińska-Więckowska, A; Tarasińska, M; Falana, K; Dembowska-Bagińska, B; Łastowska, M

2016-01-01

Rearrangements involving the ALK gene were identified in a variety of cancers, including paediatric tumour neuroblastoma where presence of ALK expression is also associated with adverse prognosis. Microarrays data indicate that ALK is expressed in another paediatric tumour - medulloblastoma. Therefore, we investigated if the ALK gene is mutated in medulloblastoma and performed simultaneously the molecular profiling of tumours. Tumours from sixty-four medulloblastoma patients were studied for detection of ALK alterations in exons 23 and 25 using Sanger method. The molecular subtypes of tumours were identified by detection of mutations in the CTNNB1 gene, monosomy 6 and by immunohistochemistry using a panel of representative antibodies. Among three ALK variants detected two resulted in intron variants (rs3738867, rs113866835) and the third one was a novel heterozygous variant c.3595A>T in exon 23 identified in the WNT type of tumour. It resulted in methionine to leucine substitution at codon position 1199 (M1199L) of the kinase domain of ALK protein. Results of analysis using three in silico algorithms confirmed the pathogenicity of this single nucleotide variation. The same gene alteration was detected in both patient and maternal peripheral blood leukocytes indicating an inherited type of the detected variant. Presence of ALK expression in tumour tissue was confirmed by immunohistochemistry. The tumour was diagnosed as classic medulloblastoma, however with visible areas of focal anaplastic features. The patient has been disease free for 6 years since diagnosis. This is the first evidence of an inherited ALK variant in the WNT type of medulloblastoma, what altogether with presence of ALK expression may point towards involvement of the ALK gene in this type of tumours.

Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy

PubMed Central

Sampaio, Hugo; Mowat, David; Roscioli, Tony

2017-01-01

Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis. PMID:28634552

Data-driven models of dominantly-inherited Alzheimer's disease progression.

PubMed

Oxtoby, Neil P; Young, Alexandra L; Cash, David M; Benzinger, Tammie L S; Fagan, Anne M; Morris, John C; Bateman, Randall J; Fox, Nick C; Schott, Jonathan M; Alexander, Daniel C

2018-05-01

See Li and Donohue (doi:10.1093/brain/awy089) for a scientific commentary on this article.Dominantly-inherited Alzheimer's disease is widely hoped to hold the key to developing interventions for sporadic late onset Alzheimer's disease. We use emerging techniques in generative data-driven disease progression modelling to characterize dominantly-inherited Alzheimer's disease progression with unprecedented resolution, and without relying upon familial estimates of years until symptom onset. We retrospectively analysed biomarker data from the sixth data freeze of the Dominantly Inherited Alzheimer Network observational study, including measures of amyloid proteins and neurofibrillary tangles in the brain, regional brain volumes and cortical thicknesses, brain glucose hypometabolism, and cognitive performance from the Mini-Mental State Examination (all adjusted for age, years of education, sex, and head size, as appropriate). Data included 338 participants with known mutation status (211 mutation carriers in three subtypes: 163 PSEN1, 17 PSEN2, and 31 APP) and a baseline visit (age 19-66; up to four visits each, 1.1 ± 1.9 years in duration; spanning 30 years before, to 21 years after, parental age of symptom onset). We used an event-based model to estimate sequences of biomarker changes from baseline data across disease subtypes (mutation groups), and a differential equation model to estimate biomarker trajectories from longitudinal data (up to 66 mutation carriers, all subtypes combined). The two models concur that biomarker abnormality proceeds as follows: amyloid deposition in cortical then subcortical regions (∼24 ± 11 years before onset); phosphorylated tau (17 ± 8 years), tau and amyloid-β changes in cerebrospinal fluid; neurodegeneration first in the putamen and nucleus accumbens (up to 6 ± 2 years); then cognitive decline (7 ± 6 years), cerebral hypometabolism (4 ± 4 years), and further regional neurodegeneration. Our models predicted symptom onset more

[Preimplantation genetic diagnosis and monogenic inherited eye diseases].

PubMed

Hlavatá, L; Ďuďáková, Ľ; Trková, M; Soldátová, I; Skalická, P; Kousal, B; Lišková, P

Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to prenatal diagnosis which aims to prevent the transmission of an inherited disorder to the progeny by implanting only embryos that do not carry genetic predisposition for a particular disease. The aim of this study is to provide an overview of eye disorders for which PGD has been carried out. The European literature search focused on best practices, ethical issues, risks and results of PGD for inherited eye disorders. PGD is performed for a number of ocular disorders; a prerequisite for its application is however, the knowledge of a disease-causing mutation(s). The main advantage of this method is that the couple is not exposed to a decision of whether or not to undergo an abortion. Qualified counselling must be provided prior to the PGD in order to completely understand the risk of disability in any child conceived, consequences of disease manifestation, and advantages as well as limitations of this method. In the group of non-syndromic eye diseases and diseases in which ocular findings dominate, PGD has been performed in European countries for aniridia, choroideremia, congenital fibrosis of extraocular muscles, Leber congenital amaurosis, ocular albinism, retinitis pigmentosa, X-linked retinoschisis, Stargardt disease, blepharophimosis-ptosis-inverse epicanthus syndrome and retinoblastoma. Sexing for X-linked or mitochondrial diseases has been carried out for blue cone monochromatism, choroideremia, familial exudative vitreoretinopathy, Leber hereditary optic neuropathy, macular dystrophy (not further specified), Norrie disease, X-linked congenital stationary night blindness, X-linked retinoschisis and nystagmus (not further specified). In recent years, there has been an increase in potential to use PGD. The spectrum of diseases for this method has widened to include severe inherited eye diseases

Dog models for blinding inherited retinal dystrophies.

PubMed

Petersen-Jones, Simon M; Komáromy, András M

2015-03-01

Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials.

Dog Models for Blinding Inherited Retinal Dystrophies

PubMed Central

Komáromy, András M.

2015-01-01

Abstract Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials. PMID:25671556

Darwin's Invention: Inheritance & the "Mad Dream" of Pangenesis

ERIC Educational Resources Information Center

McComas, William F.

2012-01-01

This article recounts the story of the development of pangenesis, a principle proposed by Charles Darwin to describe the rules of inheritance and the source of new variation, two concepts vital to his proposal of evolution by natural selection. Historical accounts such as this are infrequently included in texts and classroom discussions but can…

Sharing the cell's bounty - organelle inheritance in yeast.

PubMed

Knoblach, Barbara; Rachubinski, Richard A

2015-02-15

Eukaryotic cells replicate and partition their organelles between the mother cell and the daughter cell at cytokinesis. Polarized cells, notably the budding yeast Saccharomyces cerevisiae, are well suited for the study of organelle inheritance, as they facilitate an experimental dissection of organelle transport and retention processes. Much progress has been made in defining the molecular players involved in organelle partitioning in yeast. Each organelle uses a distinct set of factors - motor, anchor and adaptor proteins - that ensures its inheritance by future generations of cells. We propose that all organelles, regardless of origin or copy number, are partitioned by the same fundamental mechanism involving division and segregation. Thus, the mother cell keeps, and the daughter cell receives, their fair and equitable share of organelles. This mechanism of partitioning moreover facilitates the segregation of organelle fragments that are not functionally equivalent. In this Commentary, we describe how this principle of organelle population control affects peroxisomes and other organelles, and outline its implications for yeast life span and rejuvenation. © 2015. Published by The Company of Biologists Ltd.

A Mitochondrial DNA A8701G Mutation Associated with Maternally Inherited Hypertension and Dilated Cardiomyopathy in a Chinese Pedigree of a Consanguineous Marriage

PubMed Central

Zhu, Ye; Gu, Xiang; Xu, Chao

2016-01-01

Background: Cardiovascular diseases, including dilated cardiomyopathy (DCM) and hypertension, are the leading cause of death worldwide. The role of mitochondrial DNA (mtDNA) in the pathogenesis of these diseases has not been completely clarified. In this study, we evaluate whether A8701G mutation is associated with maternally inherited hypertension and DCM in a Chinese pedigree of a consanguineous marriage. Methods: Fourteen subjects in a three-generation Han Chinese family with hypertension and DCM, in which consanguineous marriage was present in the parental generation, were interviewed. We divided all the family members into case (7 maternal members) and control group (7 nonmaternal members) for comparison. Clinical evaluations and sequence analysis of mtDNA were obtained from all participants. Frequency differences between maternal and nonmaternal members were tested to locate the disease-associated mutations. Results: The majority of the family members presented with a maternal inheritance of hypertension and DCM. Sequence analysis of mtDNA in this pedigree identified eight mtDNA mutations. Among the mutations identified, there was only one significant mutation: A8701G (P = 0.005), which is a homoplasmic mitochondrial missense mutation in all the matrilineal relatives. There was no clear evidence for any synergistic effects between A8701G and other mutations. Conclusions: A8701G mutation may act as an inherited risk factor for the matrilineal transmission of hypertension and DCM in conjunction with genetic disorders caused by consanguineous marriage. PMID:26831225

Epigenetic variation, inheritance, and parent-of-origin effects of cytosine methylation in maize (Zea mays).

PubMed

Lauria, Massimiliano; Piccinini, Sara; Pirona, Raul; Lund, Gertrud; Viotti, Angelo; Motto, Mario

2014-03-01

Pure epigenetic variation, or epigenetic variation that is independent of genetic context, may provide a mechanism for phenotypic variation in the absence of DNA mutations. To estimate the extent of pure epigenetic variation within and across generations and to identify the DNA regions targeted, a group of eight plants derived from a highly inbred line of maize (Zea mays) was analyzed by the methylation-sensitive amplified polymorphism (MSAP) technique. We found that cytosine methylation (mC) differences among individuals accounted for up to 7.4% of CCGG sites investigated by MSAP. Of the differentially methylated fragments (DMFs) identified in the S0 generation, ∼12% were meiotically inherited for at least six generations. We show that meiotically heritable mC variation was consistently generated for an average of 0.5% CCGG sites per generation and that it largely occurred somatically. We provide evidence that mC variation can be established and inherited in a parent-of-origin manner, given that the paternal lineage is more prone to both forward and reverse mC changes. The molecular characterization of selected DMFs revealed that the variation was largely determined by CG methylation changes that map within gene regions. The expression analysis of genes overlapping with DMFs did not reveal an obvious correlation between mC variation and transcription, reinforcing the idea that the primary function of gene-body methylation is not to control gene expression. Because this study focuses on epigenetic variation in field-grown plants, the data presented herein pertain to spontaneous epigenetic changes of the maize genome in a natural context.

Epigenetic Variation, Inheritance, and Parent-of-Origin Effects of Cytosine Methylation in Maize (Zea mays)

PubMed Central

Lauria, Massimiliano; Piccinini, Sara; Pirona, Raul; Lund, Gertrud; Viotti, Angelo; Motto, Mario

2014-01-01

Pure epigenetic variation, or epigenetic variation that is independent of genetic context, may provide a mechanism for phenotypic variation in the absence of DNA mutations. To estimate the extent of pure epigenetic variation within and across generations and to identify the DNA regions targeted, a group of eight plants derived from a highly inbred line of maize (Zea mays) was analyzed by the methylation-sensitive amplified polymorphism (MSAP) technique. We found that cytosine methylation (mC) differences among individuals accounted for up to 7.4% of CCGG sites investigated by MSAP. Of the differentially methylated fragments (DMFs) identified in the S0 generation, ∼12% were meiotically inherited for at least six generations. We show that meiotically heritable mC variation was consistently generated for an average of 0.5% CCGG sites per generation and that it largely occurred somatically. We provide evidence that mC variation can be established and inherited in a parent-of-origin manner, given that the paternal lineage is more prone to both forward and reverse mC changes. The molecular characterization of selected DMFs revealed that the variation was largely determined by CG methylation changes that map within gene regions. The expression analysis of genes overlapping with DMFs did not reveal an obvious correlation between mC variation and transcription, reinforcing the idea that the primary function of gene-body methylation is not to control gene expression. Because this study focuses on epigenetic variation in field-grown plants, the data presented herein pertain to spontaneous epigenetic changes of the maize genome in a natural context. PMID:24374354

Interactions Between QTL SAP6 and SU91 on Resistance to Common Bacterial Blight in Red Kidney Bean and Pinto Bean Populations

USDA-ARS?s Scientific Manuscript database

Resistance to common bacterial blight in common bean is a complex trait that is quantitatively inherited. We examined the interaction between two independent QTL, SAP6 and SU91, which condition resistance to CBB.The QTL were studied in a pinto bean F2 population a cross between Othello (sap6 sap6 //...

The OncoArray Consortium: a Network for Understanding the Genetic Architecture of Common Cancers

PubMed Central

Amos, Christopher I.; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R.; Gayther, Simon A.; Casey, Graham; Hunter, David J.; Sellers, Thomas A.; Gruber, Stephen B.; Dunning, Alison M.; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B.; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A.; Hazelett, Dennis J.; Bojesen, Stig E.; Caga-Anan, Charlisse; Haiman, Christopher A.; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J.; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E.; Couch, Fergus J.; Forman, Judith L.; Giles, Graham G.; Conti, David V.; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske, Irene; Hicks, Belynda D.; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline B.; Soucy, Penny; Manz, Judith; Cunningham, Julie M.; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel M.; Lindström, Sara; Adams, Marcia; McKay, James D.; Phelan, Catherine M.; Benlloch, Sara; Kelemen, Linda E.; Brennan, Paul; Riggan, Marjorie; O’Mara, Tracy A.; Shen, Hongbin; Shi, Yongyong; Thompson, Deborah J.; Goodman, Marc T.; Nielsen, Sune F.; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L.; Shelford, Tameka; Edlund, Christopher K.; Taylor, Jack A.; Field, John K.; Park, Sue K.; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J.; Marchini, Jonathan; Al Olama, Ali Amin; Peters, Ulrike; Eeles, Rosalind A.; Seldin, Michael F.; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C.; Pharoah, Paul D.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Simard, Jacques; Easton, Douglas F.

2016-01-01

Background Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. Methods The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. Impact Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. PMID:27697780

Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity

PubMed Central

2013-01-01

Background Ancestral environmental exposures to a variety of environmental factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The present work examined the potential transgenerational actions of the insecticide dichlorodiphenyltrichloroethane (DDT) on obesity and associated disease. Methods Outbred gestating female rats were transiently exposed to a vehicle control or DDT and the F1 generation offspring bred to generate the F2 generation and F2 generation bred to generate the F3 generation. The F1 and F3 generation control and DDT lineage rats were aged and various pathologies investigated. The F3 generation male sperm were collected to investigate methylation between the control and DDT lineage male sperm. Results The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats were not found to develop obesity. The F1 generation DDT lineage animals did develop kidney disease, prostate disease, ovary disease and tumor development as adults. Interestingly, the F3 generation (great grand-offspring) had over 50% of males and females develop obesity. Several transgenerational diseases previously shown to be associated with metabolic syndrome and obesity were observed in the testis, ovary and kidney. The transgenerational transmission of disease was through both female (egg) and male (sperm) germlines. F3 generation sperm epimutations, differential DNA methylation regions (DMR), induced by DDT were identified. A number of the genes associated with the DMR have previously been shown to be associated with obesity. Conclusions Observations indicate ancestral exposure to DDT can promote obesity and associated disease transgenerationally. The etiology of disease such as obesity may be in part due to environmentally induced epigenetic transgenerational inheritance. PMID:24228800

Information accumulation system by inheritance and diffusion

NASA Astrophysics Data System (ADS)

Shin, J. K.

2009-09-01

This paper suggests a new model, called as the IAS (Information Accumulation System), for the description of the dynamic process that people use to accumulate their information (knowledge or opinion) for specific issues. Using the concept of information, both the internal and the external mechanism of the opinion dynamics are treated on a unified frame. The information is quantified as a real number with fixed bounds. New concepts, such as inheritance and differential absorption, are incorporated in IAS in addition to the conventional diffusive interaction between people. Thus, the dynamics of the IAS are governed by following three factors: inheritance rate, diffusivity and absorption rate. The original set of equations was solved with an agent based modeling technique. In addition, the individual equations for each of the agents were assembled and transformed into a set of equations for the ensemble averages, which are greatly reduced in number and can be solved analytically. The example simulations showed interesting results such as the critical behavior with respect to diffusivity, the information polarization out of zero-sum news and the dependence of the solutions on the initial conditions alone. The results were speculated in relation to today’s modern society where the diffusivity of information has been greatly increased through the internet and mobile phones.

Inheritance of fresh-cut fruit quality attributes in Capsicum

USDA-ARS?s Scientific Manuscript database

The fresh-cut fruit and vegetable industry has expanded rapidly during the past decade, due to freshness, convenience and the high nutrition that fresh-cut produce offers to consumers. The current report evaluates the inheritance of postharvest attributes that contribute to pepper fresh-cut product...

Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy

PubMed Central

Sames, Lori; Moore, Allison; Arnold, Renee; Ekins, Sean

2014-01-01

Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can

Segregation analysis of prostate cancer in France: evidence for autosomal dominant inheritance and residual brother-brother dependence.

PubMed

Valeri, A; Briollais, L; Azzouzi, R; Fournier, G; Mangin, P; Berthon, P; Cussenot, O; Demenais, F

2003-03-01

Four segregation analyses concerning prostate cancer (CaP), three conducted in the United States and one in Northern Europe, have shown evidence for a dominant major gene but with different parameter estimates. A recent segregation analysis of Australian pedigrees has found a better fit of a two-locus model than single-locus models. This model included a dominantly inherited increased risk that was greater at younger ages and a recessively inherited or X-linked increased risk that was greater at older ages. Recent linkage analyses have led to the detection of at least 8 CaP predisposing genes, suggesting a complex inheritance and genetic heterogeneity. To assess the nature of familial aggregation of prostate cancer in France, segregation analysis was conducted in 691 families ascertained through 691 CaP patients, recruited from three French hospitals and unselected with respect to age at diagnosis, clinical stage or family history. This mode of family inclusion, without any particular selection of the probands, is unique, as probands from all previous analyses were selected according to various criteria. Segregation analysis was carried out using the logistic hazard regressive model, as incorporated in the REGRESS program, which can accommodate a major gene effect, residual familial dependences of any origin (genetic and/or environmental), and covariates, while including survival analysis concepts. Segregation analysis showed evidence for the segregation of an autosomal dominant gene (allele frequency of 0.03%) with an additional brother-brother dependence. The estimated cumulative risks of prostate cancer by age 85 years, among subjects with the at-risk genotype, were 86% in the fathers' generation and 99% in the probands' generation. This study supports the model of Mendelian transmission of a rare autosomal dominant gene with high penetrance, and demonstrates that additional genetic and/or common sibling environmental factors are involved to account for the

Plants and their bioactive compounds with the potential to enhance mechanisms of inherited cardiac regeneration.

PubMed

Zhou, Zhen; Li, Dianbin; Zhou, Hua; Lin, Xiaoli; Li, Censing; Tang, Mingfeng; Feng, Zhou; Li, Ming

2015-06-01

This article reviews the current progress and research indications in the application of natural plant compounds with the potential for the treatment of cardiovascular diseases. Our understanding of how to apply natural plant compounds to enhance mechanisms of inherited cardiac regeneration, which is physiologically pertinent to myocyte turnover or minor cardiac repair, for substantial cardiac regeneration to repair pathological heart injuries is discussed. Although significant progress has been made in the application of natural plant compounds for therapy of heart diseases, the understanding or the application of these compounds specifically for enhancing mechanisms of inherited cardiac regeneration for the treatment of cardiovascular diseases is little. Recent recognition of some natural plant compounds that can repair damaged myocardial tissues through enhancing mechanisms of inherited cardiac regeneration has offered an alternative for clinical translation. Application of natural plant compounds, which show the activity of manipulating gene expressions in such a way to enhance mechanisms of inherited cardiac regeneration for cardiac repair, may provide a promising strategy for the reconstruction of damaged cardiac tissues due to cardiovascular diseases. Georg Thieme Verlag KG Stuttgart · New York.

Blue Pattern Flower in Common Bean Expressed by Interaction of Prpi-2 with a New Gene tbp

USDA-ARS?s Scientific Manuscript database

The inheritance of blue pattern flower (BPF) expression was investigated in common bean (Phaseolus vulgaris L.). The BPF trait was derived from accession line G07262, and the flowers express blue banner petal and white wings with blue veins. Crosses between a BPF stock and three other parents - t ...

PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

ERIC Educational Resources Information Center

CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

Gynaecological and obstetric management of women with inherited bleeding disorders.

PubMed

Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2006-10-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen

Gynaecological and obstetric management of women with inherited bleeding disorders.

PubMed

Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2005-07-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen

[Gene method for inconsistent hydrological frequency calculation. I: Inheritance, variability and evolution principles of hydrological genes].

PubMed

Xie, Ping; Wu, Zi Yi; Zhao, Jiang Yan; Sang, Yan Fang; Chen, Jie

2018-04-01

A stochastic hydrological process is influenced by both stochastic and deterministic factors. A hydrological time series contains not only pure random components reflecting its inheri-tance characteristics, but also deterministic components reflecting variability characteristics, such as jump, trend, period, and stochastic dependence. As a result, the stochastic hydrological process presents complicated evolution phenomena and rules. To better understand these complicated phenomena and rules, this study described the inheritance and variability characteristics of an inconsistent hydrological series from two aspects: stochastic process simulation and time series analysis. In addition, several frequency analysis approaches for inconsistent time series were compared to reveal the main problems in inconsistency study. Then, we proposed a new concept of hydrological genes origined from biological genes to describe the inconsistent hydrolocal processes. The hydrologi-cal genes were constructed using moments methods, such as general moments, weight function moments, probability weight moments and L-moments. Meanwhile, the five components, including jump, trend, periodic, dependence and pure random components, of a stochastic hydrological process were defined as five hydrological bases. With this method, the inheritance and variability of inconsistent hydrological time series were synthetically considered and the inheritance, variability and evolution principles were fully described. Our study would contribute to reveal the inheritance, variability and evolution principles in probability distribution of hydrological elements.

Neonatal Marfan Syndrome: Report of a Case with an Inherited Splicing Mutation outside the Neonatal Domain

PubMed Central

Le Gloan, Laurianne; Hauet, Quentin; David, Albert; Hanna, Nadine; Arfeuille, Chloé; Arnaud, Pauline; Boileau, Catherine; Romefort, Bénédicte; Benbrik, Nadir; Gournay, Véronique; Joram, Nicolas; Baron, Olivier; Isidor, Bertrand

2016-01-01

We report a child and her mother affected by Marfan syndrome. The child presented with a phenotype of neonatal Marfan syndrome, revealed by acute and refractory heart failure, finally leading to death within the first 4 months of life. Her mother had a common clinical presentation. Genetic analysis revealed an inherited FBN1 mutation. This intronic mutation (c.6163+3_6163+6del), undescribed to date, leads to exon 49 skipping, corresponding to in-frame deletion of 42 amino acids (p.Ile2014_Asp2055del). FBN1 next-generation sequencing did not show any argument for mosaicism. Association in the same family of severe neonatal and classical Marfan syndrome illustrates the intrafamilial phenotype variability. PMID:27022329

Neonatal Marfan Syndrome: Report of a Case with an Inherited Splicing Mutation outside the Neonatal Domain.

PubMed

Le Gloan, Laurianne; Hauet, Quentin; David, Albert; Hanna, Nadine; Arfeuille, Chloé; Arnaud, Pauline; Boileau, Catherine; Romefort, Bénédicte; Benbrik, Nadir; Gournay, Véronique; Joram, Nicolas; Baron, Olivier; Isidor, Bertrand

2016-02-01

We report a child and her mother affected by Marfan syndrome. The child presented with a phenotype of neonatal Marfan syndrome, revealed by acute and refractory heart failure, finally leading to death within the first 4 months of life. Her mother had a common clinical presentation. Genetic analysis revealed an inherited FBN1 mutation. This intronic mutation (c.6163+3_6163+6del), undescribed to date, leads to exon 49 skipping, corresponding to in-frame deletion of 42 amino acids (p.Ile2014_Asp2055del). FBN1 next-generation sequencing did not show any argument for mosaicism. Association in the same family of severe neonatal and classical Marfan syndrome illustrates the intrafamilial phenotype variability.

Sarcomere protein gene mutations and inherited heart disease: a beta-cardiac myosin heavy chain mutation causing endocardial fibroelastosis and heart failure.

PubMed

Kamisago, Mitsuhiro; Schmitt, Joachim P; McNamara, Dennis; Seidman, Christine; Seidman, J G

2006-01-01

Inherited human cardiomyopathies often lead to heart failure. A common feature of these conditions is that affected individuals can express the disease causing mutations for many years without showing clinical signs of the disease. Previous studies have demonstrated that sarcomere protein gene mutations can cause either dilated cardiomyopathy or hypertrophic cardiomyopathy. Here we demonstrate that the Arg442His missense mutation in beta-cardiac myosin heavy chain (betaMHC) causes dilated cardiomyopathy, endocardial fibroelastosis and heart failure at a very early age. Using standard genetic engineering tools we and others have made murine models by introducing human disease causing mutations into mice. The central hypothesis of these studies has been that by identifying the pathophysiological pathways activated by these mutations we can define enzymatic activities that are modified during the disease process and which may be involved in pathways that involve more common forms of cardiac disease. Murine models bearing different mutant myosins are being used to address whether each disease causing mutant betaMHC activates the same or different cellular pathways. Dissecting the molecular pathways modulated by mutations in sarcomere protein genes as well as other genes has already demonstrated that there are multiple pathways leading to cardiac remodelling and heart failure. Defining the mechanisms by which mutations in the same genes activate different cellular pathways remains an important question.

Reproductive Parasitism: Maternally Inherited Symbionts in a Biparental World

PubMed Central

Hurst, Gregory D.D.; Frost, Crystal L.

2015-01-01

Most species of insect, and many other plants and animals, carry maternally heritable microorganisms—viruses, bacteria, unicellular eukaryotes, and fungi that pass from a female host to her progeny. Maternal inheritance establishes a correlation between the fitness of symbiont and host female, which can select for the symbiont to contribute to host fitness. Nevertheless, its lack of transmission through male hosts places the symbiont in conflict with biparentally inherited nuclear genes. In this review, we first examine how this conflict is manifest in selection to promote the production and survival of infected female hosts and gametes. We then examine how the distorted population sex ratios that they produce may affect host reproductive ecology, and thus the intensity of other conflicts associated with sexual reproduction. Finally, we examine evolved host responses to symbiont manipulation. We argue that the unusual intensity of symbiont–host conflict generates extreme selection pressures that can drive changes in sex-determination systems, the basic pathway through which males and females are constructed. PMID:25934011

The mechanisms of feature inheritance as predicted by a systems-level model of visual attention and decision making.

PubMed

Hamker, Fred H

2008-07-15

Feature inheritance provides evidence that properties of an invisible target stimulus can be attached to a following mask. We apply a systemslevel model of attention and decision making to explore the influence of memory and feedback connections in feature inheritance. We find that the presence of feedback loops alone is sufficient to account for feature inheritance. Although our simulations do not cover all experimental variations and focus only on the general principle, our result appears of specific interest since the model was designed for a completely different purpose than to explain feature inheritance. We suggest that feedback is an important property in visual perception and provide a description of its mechanism and its role in perception.

Beyond DNA: integrating inclusive inheritance into an extended theory of evolution.

PubMed

Danchin, Étienne; Charmantier, Anne; Champagne, Frances A; Mesoudi, Alex; Pujol, Benoit; Blanchet, Simon

2011-06-17

Many biologists are calling for an 'extended evolutionary synthesis' that would 'modernize the modern synthesis' of evolution. Biological information is typically considered as being transmitted across generations by the DNA sequence alone, but accumulating evidence indicates that both genetic and non-genetic inheritance, and the interactions between them, have important effects on evolutionary outcomes. We review the evidence for such effects of epigenetic, ecological and cultural inheritance and parental effects, and outline methods that quantify the relative contributions of genetic and non-genetic heritability to the transmission of phenotypic variation across generations. These issues have implications for diverse areas, from the question of missing heritability in human complex-trait genetics to the basis of major evolutionary transitions.

Constitutive Overexpression of Human Erythropoietin Protects the Mouse Retina against Induced But Not Inherited Retinal Degeneration

PubMed Central

Grimm, Christian; Wenzel, Andreas; Stanescu, Dinu; Samardzija, Marijana; Hotop, Svenja; Groszer, Mathias; Naash, Muna; Gassmann, Max; Remé, Charlotte

2010-01-01

Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application of recombinant human Epo (huEpo) protects the mouse retina against light-induced degeneration by inhibiting photoreceptor cell apoptosis. Because photoreceptor apoptosis is also the common path to cell loss in retinal dystrophies such as retinitis pigmentosa (RP), we tested whether high levels of huEpo would reduce apoptotic cell death in two mouse models of human RP. We combined the two respective mutant mouse lines with a transgenic line (tg6) that constitutively overexpresses huEpo mainly in neural tissues. Transgenic expression of huEpo caused constitutively high levels of Epo in the retina and protected photoreceptors against light-induced degeneration; however, the presence of high levels of huEpo did not affect the course or the extent of retinal degeneration in a light-independent (rd1) and a light-accelerated (VPP) mouse model of RP. Similarly, repetitive intraperitoneal injections of recombinant huEpo did not protect the retina in the rd1 and the VPP mouse. Lack of neuroprotection by Epo in the two models of inherited retinal degeneration was not caused by adaptational downregulation of Epo receptor. Our results suggest that apoptotic mechanisms during acute, light-induced photoreceptor cell death differ from those in genetically based retinal degeneration. Therapeutic intervention with cell death in inherited retinal degeneration may therefore require different drugs and treatments. PMID:15215287

The role of family social background and inheritance in later life volunteering: Evidence from SHARE-Israel

PubMed Central

Youssim, Iaroslav; Hank, Karsten; Litwin, Howard

2014-01-01

Building on a tripartite model of capitals necessary to perform productive activities and on work suggesting that cumulative (dis-) advantage processes are important mechanisms for life-course inequalities, our study set out to investigate the potential role of family social background and inheritance in later-life volunteering. We hypothesized that older individuals who inherited work-relevant economic and cultural capitals from their family of origin are more likely to be engaged in voluntary activities than their counterparts with a less advantageous family social background. Our main findings from the analysis of a representative sample of community-dwelling Israelis aged 50 and over provide strong support for this hypothesis: the likelihood to volunteer is significantly higher among those who received substantial financial transfers from their family of origin (‘inherited economic capital’) and among those having a ‘white collar’ parental background (‘inherited cultural capital’). We conclude with perspectives for future research. PMID:25651548

The role of family social background and inheritance in later life volunteering: evidence from SHARE-Israel.

PubMed

Youssim, Iaroslav; Hank, Karsten; Litwin, Howard

2015-01-01

Building on a tripartite model of capitals necessary to perform productive activities and on work suggesting that cumulative (dis-)advantage processes are important mechanisms for life course inequalities, our study set out to investigate the potential role of family social background and inheritance in later life volunteering. We hypothesized that older individuals who inherited work-relevant economic and cultural capitals from their family of origin are more likely to be engaged in voluntary activities than their counterparts with a less advantageous family social background. Our main findings from the analysis of a representative sample of community-dwelling Israelis aged 50 and over provide strong support for this hypothesis: the likelihood to volunteer is significantly higher among those who received substantial financial transfers from their family of origin ("inherited economic capital") and among those having a "white collar" parental background ("inherited cultural capital"). We conclude with perspectives for future research. © The Author(s) 2014.

Changes in bone structure of Corriedale sheep with inherited rickets: a peripheral quantitative computed tomography assessment.

PubMed

Dittmer, Keren E; Firth, Elwyn C; Thompson, Keith G; Marshall, Jonathan C; Blair, Hugh T

2011-03-01

An inherited skeletal disease with gross and microscopic features of rickets has been diagnosed in Corriedale sheep in New Zealand. The aim of this study was to quantify the changes present in tibia from sheep with inherited rickets using peripheral quantitative computed tomography. In affected sheep, scans in the proximal tibia, where metaphysis becomes diaphysis, showed significantly greater trabecular bone mineral content (BMC) and bone mineral density (BMD). The sheep with inherited rickets had significantly greater BMC and bone area in the mid-diaphysis of the proximal tibia compared to control sheep. However, BMD in the mid-diaphysis was significantly less in affected sheep than in controls, due to the greater cortical area and lower voxel density values in affected sheep. From this it was concluded that the increased strain on under-mineralised bone in sheep with inherited rickets led to increased bone mass in an attempt to improve bone strength. Copyright © 2010 Elsevier Ltd. All rights reserved.

Uptake of Predictive Genetic Testing and Cardiac Evaluation for Children at Risk for an Inherited Arrhythmia or Cardiomyopathy.

PubMed

Christian, Susan; Atallah, Joseph; Clegg, Robin; Giuffre, Michael; Huculak, Cathleen; Dzwiniel, Tara; Parboosingh, Jillian; Taylor, Sherryl; Somerville, Martin

2018-02-01

Predictive genetic testing in minors should be considered when clinical intervention is available. Children who carry a pathogenic variant for an inherited arrhythmia or cardiomyopathy require regular cardiac screening and may be prescribed medication and/or be told to modify their physical activity. Medical genetics and pediatric cardiology charts were reviewed to identify factors associated with uptake of genetic testing and cardiac evaluation for children at risk for long QT syndrome, hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. The data collected included genetic diagnosis, clinical symptoms in the carrier parent, number of children under 18 years of age, age of children, family history of sudden cardiac arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each child. We identified 97 at risk children from 58 families found to carry a pathogenic variant for one of these conditions. Sixty six percent of the families pursued genetic testing and 73% underwent cardiac screening when it was recommended. Declining predictive genetic testing was significantly associated with genetic specialist recommendation (p < 0.001) and having an asymptomatic carrier father (p = 0.006). Cardiac evaluation was significantly associated with uptake of genetic testing (p = 0.007). This study provides a greater understanding of factors associated with uptake of genetic testing and cardiac evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It also identifies a need to educate families about the importance of cardiac evaluation even in the absence of genetic testing.

Identification of Novel, Inherited Genetic Markers for Aggressive PCa in European and African Americans Using Whole Genome Sequencing

DTIC Science & Technology

2013-09-01

DATES COVERED (From - To) 22 August 2012 – 21 August 2013 4. TITLE AND SUBTITLE Identification of Novel, Inherited Genetic Markers for Aggressive... Inherited markers of aggressive PCa could be used for screening and diagnosis of aggressive PCa at an early stage while reducing over-diagnosis and...treatment for others. The overall hypothesis is that inherited sequence variants in the genome are associated with a lethal (aggressive) form of PCa but not

Modelling the co-evolution of indirect genetic effects and inherited variability.

PubMed

Marjanovic, Jovana; Mulder, Han A; Rönnegård, Lars; Bijma, Piter

2018-03-28

When individuals interact, their phenotypes may be affected not only by their own genes but also by genes in their social partners. This phenomenon is known as Indirect Genetic Effects (IGEs). In aquaculture species and some plants, however, competition not only affects trait levels of individuals, but also inflates variability of trait values among individuals. In the field of quantitative genetics, the variability of trait values has been studied as a quantitative trait in itself, and is often referred to as inherited variability. Such studies, however, consider only the genetic effect of the focal individual on trait variability and do not make a connection to competition. Although the observed phenotypic relationship between competition and variability suggests an underlying genetic relationship, the current quantitative genetic models of IGE and inherited variability do not allow for such a relationship. The lack of quantitative genetic models that connect IGEs to inherited variability limits our understanding of the potential of variability to respond to selection, both in nature and agriculture. Models of trait levels, for example, show that IGEs may considerably change heritable variation in trait values. Currently, we lack the tools to investigate whether this result extends to variability of trait values. Here we present a model that integrates IGEs and inherited variability. In this model, the target phenotype, say growth rate, is a function of the genetic and environmental effects of the focal individual and of the difference in trait value between the social partner and the focal individual, multiplied by a regression coefficient. The regression coefficient is a genetic trait, which is a measure of cooperation; a negative value indicates competition, a positive value cooperation, and an increasing value due to selection indicates the evolution of cooperation. In contrast to the existing quantitative genetic models, our model allows for co-evolution of

Mitochondrial DNA Polymerase W748S Mutation: A Common Cause of Autosomal Recessive Ataxia with Ancient European Origin

PubMed Central

Hakonen, Anna H.; Heiskanen, Silja; Juvonen, Vesa; Lappalainen, Ilse; Luoma, Petri T.; Rantamäki, Maria; Goethem, Gert Van; Löfgren, Ann; Hackman, Peter; Paetau, Anders; Kaakkola, Seppo; Majamaa, Kari; Varilo, Teppo; Udd, Bjarne; Kääriäinen, Helena; Bindoff, Laurence A.; Suomalainen, Anu

2005-01-01

Mutations in the catalytic subunit of the mitochondrial DNA polymerase γ (POLG) have been found to be an important cause of neurological disease. Recently, we and collaborators reported a new neurodegenerative disorder with autosomal recessive ataxia in four patients homozygous for two amino acid changes in POLG: W748S in cis with E1143G. Here, we studied the frequency of this allele and found it to be among the most common genetic causes of inherited ataxia in Finland. We identified 27 patients with mitochondrial recessive ataxia syndrome (MIRAS) from 15 Finnish families, with a carrier frequency in the general population of 1:125. Since the mutation pair W748S+E1143G has also been described in European patients, we examined the haplotypes of 13 non-Finnish, European patients with the W748S mutation. Haplotype analysis revealed that all the chromosomes carrying these two changes, in patients from Finland, Norway, the United Kingdom, and Belgium, originate from a common ancient founder. In Finland and Norway, long, common, northern haplotypes, outside the core haplotype, could be identified. Despite having identical homozygous mutations, the Finnish patients with this adult- or juvenile-onset disease had surprisingly heterogeneous phenotypes, albeit with a characteristic set of features, including ataxia, peripheral neuropathy, dysarthria, mild cognitive impairment, involuntary movements, psychiatric symptoms, and epileptic seizures. The high carrier frequency in Finland, the high number of patients in Norway, and the ancient European founder chromosome indicate that this newly identified ataxia should be considered in the first-line differential diagnosis of progressive ataxia syndromes. PMID:16080118

A Novel Targeted Approach for Noninvasive Detection of Paternally Inherited Mutations in Maternal Plasma.

PubMed

van den Oever, Jessica M E; van Minderhout, Ivonne J H M; Harteveld, Cornelis L; den Hollander, Nicolette S; Bakker, Egbert; van der Stoep, Nienke; Boon, Elles M J

2015-09-01

The challenge in noninvasive prenatal diagnosis for monogenic disorders lies in the detection of low levels of fetal variants in the excess of maternal cell-free plasma DNA. Next-generation sequencing, which is the main method used for noninvasive prenatal testing and diagnosis, can overcome this challenge. However, this method may not be accessible to all genetic laboratories. Moreover, shotgun next-generation sequencing as, for instance, currently applied for noninvasive fetal trisomy screening may not be suitable for the detection of inherited mutations. We have developed a sensitive, mutation-specific, and fast alternative for next-generation sequencing-mediated noninvasive prenatal diagnosis using a PCR-based method. For this proof-of-principle study, noninvasive fetal paternally inherited mutation detection was performed using cell-free DNA from maternal plasma. Preferential amplification of the paternally inherited allele was accomplished through a personalized approach using a blocking probe against maternal sequences in a high-resolution melting curve analysis-based assay. Enhanced detection of the fetal paternally inherited mutation was obtained for both an autosomal dominant and a recessive monogenic disorder by blocking the amplification of maternal sequences in maternal plasma. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Inheritance of Mesotrione Resistance in an Amaranthus tuberculatus (var. rudis) Population from Nebraska, USA

PubMed Central

Oliveira, Maxwel C.; Gaines, Todd A.; Jhala, Amit J.; Knezevic, Stevan Z.

2018-01-01

A population of Amaranthus tuberculatus (var. rudis) evolved resistance to 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicides (mesotrione, tembotrione, and topramezone) in Nebraska. The level of resistance was the highest to mesotrione, and the mechanism of resistance in this population is metabolism-based likely via cytochrome P450 enzymes. The increasing number of weeds resistant to herbicides warrants studies on the ecology and evolutionary factors contributing for resistance evolution, including inheritance of resistance traits. In this study, we investigated the genetic control of mesotrione resistance in an A. tuberculatus population from Nebraska, USA. Results showed that reciprocal crosses in the F1 families exhibited nuclear inheritance, which allows pollen movement carrying herbicide resistance alleles. The mode of inheritance varied from incomplete recessive to incomplete dominance depending upon the F1 family. Observed segregation patterns for the majority of the F2 and back-cross susceptible (BC/S) families did not fit to a single major gene model. Therefore, multiple genes are likely to confer metabolism-based mesotrione resistance in this A. tuberculatus population from Nebraska. The results of this study aid to understand the genetics and inheritance of a non-target-site based mesotrione resistant A. tuberculatus population from Nebraska, USA. PMID:29456544

A Common Ancestral Mutation in CRYBB3 Identified in Multiple Consanguineous Families with Congenital Cataracts

PubMed Central

Irum, Bushra; Khan, Arif O.; Wang, Qiwei; Li, David; Khan, Asma A.; Husnain, Tayyab; Akram, Javed; Riazuddin, Sheikh

2016-01-01

Purpose This study was performed to investigate the genetic determinants of autosomal recessive congenital cataracts in large consanguineous families. Methods Affected individuals underwent a detailed ophthalmological examination and slit-lamp photographs of the cataractous lenses were obtained. An aliquot of blood was collected from all participating family members and genomic DNA was extracted from white blood cells. Initially, a genome-wide scan was performed with genomic DNAs of family PKCC025 followed by exclusion analysis of our familial cohort of congenital cataracts. Protein-coding exons of CRYBB1, CRYBB2, CRYBB3, and CRYBA4 were sequenced bidirectionally. A haplotype was constructed with SNPs flanking the causal mutation for affected individuals in all four families, while the probability that the four familial cases have a common founder was estimated using EM and CHM-based algorithms. The expression of Crybb3 in the developing murine lens was investigated using TaqMan assays. Results The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis localized the causal phenotype in family PKCC025 to chromosome 22q with statistically significant two-point logarithm of odds (LOD) scores. Subsequently, we localized three additional families, PKCC063, PKCC131, and PKCC168 to chromosome 22q. Bidirectional Sanger sequencing identified a missense variation: c.493G>C (p.Gly165Arg) in CRYBB3 that segregated with the disease phenotype in all four familial cases. This variation was not found in ethnically matched control chromosomes, the NHLBI exome variant server, or the 1000 Genomes or dbSNP databases. Interestingly, all four families harbor a unique disease haplotype that strongly suggests a common founder of the causal mutation (p<1.64E-10). We observed expression of Crybb3 in the mouse lens as early as embryonic day 15 (E15), and expression remained relatively steady throughout

Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations, and Genotype/Phenotype Correlations

PubMed Central

Martorana, Davide; Bonatti, Francesco; Mozzoni, Paola; Vaglio, Augusto; Percesepe, Antonio

2017-01-01

Autoinflammatory diseases (AIDs) are a genetically heterogeneous group of diseases caused by mutations of genes encoding proteins, which play a pivotal role in the regulation of the inflammatory response. In the pathogenesis of AIDs, the role of the genetic background is triggered by environmental factors through the modulation of the innate immune system. Monogenic AIDs are characterized by Mendelian inheritance and are caused by highly penetrant genetic variants in single genes. During the last years, remarkable progress has been made in the identification of disease-associated genes by using new technologies, such as next-generation sequencing, which has allowed the genetic characterization in undiagnosed patients and in sporadic cases by means of targeted resequencing of a gene panel and whole exome sequencing. In this review, we delineate the genetics of the monogenic AIDs, report the role of the most common gene mutations, and describe the evidences of the most sound genotype/phenotype correlations in AID. PMID:28421071

Distinct mutations with different inheritance mode caused similar retinal dystrophies in one family: a demonstration of the importance of genetic annotations in complicated pedigrees.

PubMed

Chen, Xue; Sheng, Xunlun; Liu, Yani; Li, Zili; Sun, Xiantao; Jiang, Chao; Qi, Rui; Yuan, Shiqin; Wang, Xuhui; Zhou, Ge; Zhen, Yanyan; Xie, Ping; Liu, Qinghuai; Yan, Biao; Zhao, Chen

2018-05-29

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy presenting remarkable genetic heterogeneity. Genetic annotations would help with better clinical assessments and benefit gene therapy, and therefore should be recommended for RP patients. This report reveals the disease causing mutations in two RP pedigrees with confusing inheritance patterns using whole exome sequencing (WES). Twenty-five participants including eight patients from two families were recruited and received comprehensive ophthalmic evaluations. WES was applied for mutation identification. Bioinformatics annotations, intrafamilial co-segregation tests, and in silico analyses were subsequently conducted for mutation verification. All patients were clinically diagnosed with RP. The first family included two siblings born to parents with consanguineous marriage; however, no potential pathogenic variant was found shared by both patients. Further analysis revealed that the female patient carried a recurrent homozygous C8ORF37 p.W185*, while the male patient had hemizygous OFD1 p.T120A. The second family was found to segregate mutations in two genes, TULP1 and RP1. Two patients born to consanguineous marriage carried homozygous TULP1 p.R419W, while a recurrent heterozygous RP1 p.L762Yfs*17 was found in another four patients presenting an autosomal dominant inheritance pattern. Crystal structural analysis further indicated that the substitution from arginine to tryptophan at the highly conserved residue 419 of TULP1 could lead to the elimination of two hydrogen bonds between residue 419 and residues V488 and S534. All four genes, including C8ORF37, OFD1, TULP1 and RP1, have been previously implicated in RP etiology. Our study demonstrates the coexistence of diverse inheritance modes and mutations affecting distinct disease causing genes in two RP families with consanguineous marriage. Our data provide novel insights into assessments of complicated pedigrees, reinforce the

Audience Duplication in the Video Age: Changes in Prime Time Inheritance Effects between 1976 and 1985.

ERIC Educational Resources Information Center

Walker, James R.

Evaluating the impact of the changing media environment on television programming, a study examined inheritance effects--the percentage of one television program's audience that also watches the program immediately following--in network prime time programming between 1976 and 1985. Inheritance effect was calculated as the correlation between a…

Oblique contractional reactivation of inherited heterogeneities: Cause for arcuate orogens

PubMed Central

Sokoutis, D.; Willingshofer, E.; Brun, J.‐P.; Gueydan, F.; Cloetingh, S.

2017-01-01

Abstract We use lithospheric‐scale analog models to study the reactivation of pre‐existing heterogeneities under oblique shortening and its relation to the origin of arcuate orogens. Reactivation of inherited rheological heterogeneities is an important mechanism for localization of deformation in compressional settings and consequent initiation of contractional structures during orogenesis. However, the presence of an inherited heterogeneity in the lithosphere is in itself not sufficient for its reactivation once the continental lithosphere is shortened. The heterogeneity orientation is important in determining if reactivation occurs and to which extent. This study aims at giving insights on this process by means of analog experiments in which a linear lithospheric heterogeneity trends with various angles to the shortening direction. In particular, the key parameter investigated is the orientation (angle α) of a strong domain (SD) with respect to the shortening direction. Experimental results show that angles α ≥ 75° (high obliquity) allow for reactivation along the entire SD and the development of a linear orogen. For α ≤ 60° (low obliquity) the models are characterized by the development of an arcuate orogen, with the SD remaining partially non‐reactivated. These results provide a new mechanism for the origin of some arcuate orogens, in which orocline formation was not driven by indentation or subduction processes, but by oblique shortening of inherited heterogeneities, as exemplified by the Ouachita orogen of the southern U.S. PMID:28670046

Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.

PubMed

Bolton, Jennifer L; Hayward, Caroline; Direk, Nese; Lewis, John G; Hammond, Geoffrey L; Hill, Lesley A; Anderson, Anna; Huffman, Jennifer; Wilson, James F; Campbell, Harry; Rudan, Igor; Wright, Alan; Hastie, Nicholas; Wild, Sarah H; Velders, Fleur P; Hofman, Albert; Uitterlinden, Andre G; Lahti, Jari; Räikkönen, Katri; Kajantie, Eero; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G; Kaakinen, Marika; Järvelin, Marjo-Riitta; Timpson, Nicholas J; Davey Smith, George; Ring, Susan M; Evans, David M; St Pourcain, Beate; Tanaka, Toshiko; Milaneschi, Yuri; Bandinelli, Stefania; Ferrucci, Luigi; van der Harst, Pim; Rosmalen, Judith G M; Bakker, Stephen J L; Verweij, Niek; Dullaart, Robin P F; Mahajan, Anubha; Lindgren, Cecilia M; Morris, Andrew; Lind, Lars; Ingelsson, Erik; Anderson, Laura N; Pennell, Craig E; Lye, Stephen J; Matthews, Stephen G; Eriksson, Joel; Mellstrom, Dan; Ohlsson, Claes; Price, Jackie F; Strachan, Mark W J; Reynolds, Rebecca M; Tiemeier, Henning; Walker, Brian R

2014-07-01

Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

Investigating the inheritance of prolapsed nictitating membrane glands in a large canine pedigree

PubMed Central

Edelmann, Michele L.; Miyadera, Keiko; Iwabe, Simone; Komáromy, András M.

2014-01-01

Objective To investigate the inheritance of prolapsed nictitating membrane glands (PNMG) in a large pedigree of purpose-bred mongrel dogs. Animals studied Two lines of purpose-bred mongrel dogs kept at a research facility with controlled environment were analyzed for frequent occurrences of PNMG. The first line (GS line) consisted of 201 dogs, derived from one German shorthaired pointer and seven mongrel dogs. The second line (M line) was established from one mongrel dog and three miniature longhaired dachshund (MLHD) dogs followed by closed breeding practice (n = 50). The two canine lines were connected by a female dog, which contributed genetically to both lines. Procedures Medical records of all dogs were reviewed retrospectively for signalment, parental data, and the presence of PNMG. Pedigrees were constructed to facilitate assessment of inheritance. Results The overall prevalence of PNMG in the GS line was 4.0% (8/201) over a 12-year period. The prevalence in the M line was 10.0% (5/50) over 6 years, which increased to 23.1% (3/13) when only dogs aged 2 years or older were considered. Analysis of the pedigrees ruled out simple modes of Mendelian inheritance in both canine lines. Conclusion The high prevalence of PNMG in two canine lines bred and maintained under a strictly controlled environment supported the involvement of genetic risk factors. The mode of inheritance remains to be determined, but it appears to be complex and potentially multigenic. PMID:23240682

Identifying the Role of Common Interests in Online User Trust Formation

PubMed Central

Ji, Lei; Liu, Jian-Guo; Hou, Lei; Guo, Qiang

2015-01-01

Despite enormous recent efforts in detecting the mechanism of the social relation formation in online social systems, the underlying rules between the common interests and social relations are still under dispute. Do online users befriend others who have similar tastes, or do their tastes become more similar after they become friends? In this paper, we investigate the correlation between online user trust formation and their common interests, measured by the overlap rate ρ and taste similarity θ respectively. The trust relation creation time is set as the zero timestamp. The statistical results before and after the trust formation for an online network, namely Epinions, show that, the overlap rate ρ increases greatly before the trust formation, while it would increase smoothly after the creation of the trust relation. Comparing with the empirical results, two null models are presented by shuffling the temporal behaviors of online users, which suggests that the accumulation of the common interests can result in the trust formation. Furthermore, we investigate the taste similarity θ of the common interests, which can reflect the users’ preference on their common interests. The empirical results show that the taste similarity θ is rapidly increased around the day when users trust the others. That is, the similar tastes on the common interests among users lead to the trust formation. Finally, we report that the user degree can also influence the effect of the taste similarity θ on user trust formation. This work may shed some light for deeply understanding the evolution mechanism of the online social systems. PMID:26161853

Identifying the Role of Common Interests in Online User Trust Formation.

PubMed

Ji, Lei; Liu, Jian-Guo; Hou, Lei; Guo, Qiang

2015-01-01

Despite enormous recent efforts in detecting the mechanism of the social relation formation in online social systems, the underlying rules between the common interests and social relations are still under dispute. Do online users befriend others who have similar tastes, or do their tastes become more similar after they become friends? In this paper, we investigate the correlation between online user trust formation and their common interests, measured by the overlap rate ρ and taste similarity θ respectively. The trust relation creation time is set as the zero timestamp. The statistical results before and after the trust formation for an online network, namely Epinions, show that, the overlap rate ρ increases greatly before the trust formation, while it would increase smoothly after the creation of the trust relation. Comparing with the empirical results, two null models are presented by shuffling the temporal behaviors of online users, which suggests that the accumulation of the common interests can result in the trust formation. Furthermore, we investigate the taste similarity θ of the common interests, which can reflect the users' preference on their common interests. The empirical results show that the taste similarity θ is rapidly increased around the day when users trust the others. That is, the similar tastes on the common interests among users lead to the trust formation. Finally, we report that the user degree can also influence the effect of the taste similarity θ on user trust formation. This work may shed some light for deeply understanding the evolution mechanism of the online social systems.

Using lod-score differences to determine mode of inheritance: a simple, robust method even in the presence of heterogeneity and reduced penetrance.

PubMed

Greenberg, D A; Berger, B

1994-10-01

Determining the mode of inheritance is often difficult under the best of circumstances, but when segregation analysis is used, the problems of ambiguous ascertainment procedures, reduced penetrance, heterogeneity, and misdiagnosis make mode-of-inheritance determinations even more unreliable. The mode of inheritance can also be determined using a linkage-based method (maximized maximum lod score or mod score) and association-based methods, which can overcome many of these problems. In this work, we determined how much information is necessary to reliably determine the mode of inheritance from linkage data when heterogeneity and reduced penetrance are present in the data set. We generated data sets under both dominant and recessive inheritance with reduced penetrance and with varying fractions of linked and unlinked families. We then analyzed those data sets, assuming reduced penetrance, both dominant and recessive inheritance, and no heterogeneity. We investigated the reliability of two methods for determining the mode of inheritance from the linkage data. The first method examined the difference (delta) between the maximum lod scores calculated under the two mode-of-inheritance assumptions. We found that if delta was > 1.5, then the higher of the two maximum lod scores reflected the correct mode of inheritance with high reliability and that a delta of 2.5 appeared to practically guarantee a correct mode-of-inheritance inference. Furthermore, this reliability appeared to be virtually independent of alpha, the fraction of linked families in the data set, although the reliability decreased slightly as alpha fell below .50.(ABSTRACT TRUNCATED AT 250 WORDS)

Inherited Retinal Degenerative Disease Clinical Trial Network. Addendum

DTIC Science & Technology

2010-10-01

by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at approximately 200,000 individuals. RP... Retinitis Pigmentosa ). NNRI is awaiting final protocol review and HRPO approval for NNRI and the three enrolling clinical sites- the CTEC site at...acid) in individuals with autosomal dominant retinitis pigmentosa , with the ability to expand the enrollment to individuals with autosomal recessive

Individual variation in social aggression and the probability of inheritance: theory and a field test.

PubMed

Cant, Michael A; Llop, Justine B; Field, Jeremy

2006-06-01

Recent theory suggests that much of the wide variation in individual behavior that exists within cooperative animal societies can be explained by variation in the future direct component of fitness, or the probability of inheritance. Here we develop two models to explore the effect of variation in future fitness on social aggression. The models predict that rates of aggression will be highest toward the front of the queue to inherit and will be higher in larger, more productive groups. A third prediction is that, in seasonal animals, aggression will increase as the time available to inherit the breeding position runs out. We tested these predictions using a model social species, the paper wasp Polistes dominulus. We found that rates of both aggressive "displays" (aimed at individuals of lower rank) and aggressive "tests" (aimed at individuals of higher rank) decreased down the hierarchy, as predicted by our models. The only other significant factor affecting aggression rates was date, with more aggression observed later in the season, also as predicted. Variation in future fitness due to inheritance rank is the hidden factor accounting for much of the variation in aggressiveness among apparently equivalent individuals in this species.

Influence of the Inherited Glucose-6-phosphate Dehydrogenase Deficiency on the Appearance of Neonatal Hyperbilirubinemia in Southern Croatia.

PubMed

Cherepnalkovski, Anet Papazovska; Marusic, Eugenija; Piperkova, Katica; Lozic, Bernarda; Skelin, Ana; Gruev, Todor; Krzelj, Vjekoslav

2015-10-01

Neonatal hyperbilirubinemia is a common clinical manifestation of the inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to investigate the influence of the inherited G6PD deficiency on the appearance of neonatal hyperbilirubinemia in southern Croatia. The fluorescent spot test (FST) was used in a retrospective study to screen blood samples of 513 male children who had neonatal hyperbilirubinemia, of unknown cause, higher than 240 μmol/L. Fluorescence readings were performed at the beginning and at the fifth and tenth minute of incubation and were classified into three groups bright fluorescence (BF), weak fluorescence (WF) and no fluorescence (NF). Normal samples show bright fluorescence. All NF and WF samples at the fifth minute were quantitatively measured using the spectrophotometric method. Bright fluorescence was present in 461 patients (89.9%) at the fifth minute. The remaining 52 (10.1%) were quantitatively estimated using the spectrophotometric method. G6PD deficiency was observed in 38 patients (7.4%). Prevalence rate of G6PD deficiency among male newborns with hyperbilirubinemia in southern Croatia is significantly higher (p < 0.01) compared with the previously reported prevalence rate among male in general population of southern Croatia (0.75%). We recommend FST to be performed in hyperbilirubinemic newborns in southern Croatia.

Does three-dimensional electromagnetic field inherit the spacetime symmetries?

NASA Astrophysics Data System (ADS)

Cvitan, M.; Dominis Prester, P.; Smolić, I.

2016-04-01

We prove that the electromagnetic field in a (1+2)-dimensional spacetime necessarily inherits the symmetries of the spacetime metric in a large class of generalized Einstein-Maxwell theories. The Lagrangians of the studied theories have general diff-covariant gravitational part and include both the gravitational and the gauge Chern-Simons terms.

Inheritance of resistance to anti-microtubule dinitroaniline herbicides in an "intermediate" resistant biotype of Eleusine indica (Poaceae).

PubMed

Zeng, L; Baird, W V

1999-07-01

Inheritance of resistance to the anti-microtubule dinitroaniline herbicides was investigated in a goosegrass biotype displaying an intermediate level of resistance (I). Reciprocal crosses were made between the I biotype and previously characterized susceptible (S) or resistant (R) biotypes. Eight F(1) hybrids were identified, and F(2) populations were produced by selfing. The dinitroaniline-herbicide response phenotype (DRP) of F(1) plants, and F(2) seedlings was determined using a root-growth bioassay. The DRP of F(1) plants of S × I was "susceptible" (i.e., identical to the S parental plants), and the DRP of F(1) plants of I × R was "intermediate" (i.e., identical to the I parental plants). Nonparental phenotypes were not observed in F(1) plants. Results indicated susceptibility to be dominant over intermediate resistance and intermediate resistance to be dominant over high resistance. Analysis of reciprocal crosses ruled out any role for cytoplasmic inheritance. When treated at the discriminating concentration (e.g., 0.28 ppm oryzalin), F(2) seedlings of S × I were classified as either S or I phenotype, and F(2) seedlings of I × R were classified as either I or R phenotype. Again, nonparental phenotypes were not observed. The 3:1 (S:I or I:R) segregation ratios in F(2) seedlings were consistent across all eight F(2) families. The results show that dinitroaniline herbicide resistance in the I biotype of goosegrass is inherited as a single, nuclear gene. Furthermore, it suggests that dinitroaniline resistance in goosegrass is controlled by three alleles at a single locus (i.e., Drp-S, Drp-i, and Drp-r).

Something Old, Something New: Using Family History and Genetic Testing to Diagnose and Manage Athletes with Inherited Cardiovascular Disease.

PubMed

Thomas, Matthew J; Battle, Robert W

2015-07-01

A primary objective of the preparticipation physical examination is to identify athletes at increased risk for sudden cardiac arrest (SCA). Review of an athlete's family history may identify those at risk for SCA. Genetic testing for inherited cardiovascular disease has emerged as a valuable addition to the repertoire of cardiologists facing the decision of clearing athletes with concerning clinical signs and/or family histories. Genetic testing may lead to various outcomes for an athlete including: reassurance, diagnosis in those with borderline clinical features, finding disease predisposition prior to the onset of clinical signs (ie, genotype-positive/phenotype-negative), or continued uncertainty. Copyright © 2015 Elsevier Inc. All rights reserved.

Social inheritance can explain the structure of animal social networks

PubMed Central

Ilany, Amiyaal; Akçay, Erol

2016-01-01

The social network structure of animal populations has major implications for survival, reproductive success, sexual selection and pathogen transmission of individuals. But as of yet, no general theory of social network structure exists that can explain the diversity of social networks observed in nature, and serve as a null model for detecting species and population-specific factors. Here we propose a simple and generally applicable model of social network structure. We consider the emergence of network structure as a result of social inheritance, in which newborns are likely to bond with maternal contacts, and via forming bonds randomly. We compare model output with data from several species, showing that it can generate networks with properties such as those observed in real social systems. Our model demonstrates that important observed properties of social networks, including heritability of network position or assortative associations, can be understood as consequences of social inheritance. PMID:27352101

FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwide.

PubMed

van Baal, Sjozef; Kaimakis, Polynikis; Phommarinh, Manyphong; Koumbi, Daphne; Cuppens, Harry; Riccardino, Francesca; Macek, Milan; Scriver, Charles R; Patrinos, George P

2007-01-01

Frequency of INherited Disorders database (FINDbase) (http://www.findbase.org) is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Databaseaccess is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a 'database-journal'.

Learning about Inheritance in an Out-of-School Setting

ERIC Educational Resources Information Center

Dairianathan, Anne; Subramaniam, R.

2011-01-01

The purpose of this study was to investigate primary students' learning through participation in an out-of-school enrichment programme, held in a science centre, which focused on DNA and genes and whether participation in the programme led to an increased understanding of inheritance as well as promoted interest in the topic. The sample consisted…

The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.

PubMed

Amos, Christopher I; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R; Gayther, Simon A; Casey, Graham; Hunter, David J; Sellers, Thomas A; Gruber, Stephen B; Dunning, Alison M; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A; Hazelett, Dennis J; Bojesen, Stig E; Caga-Anan, Charlisse; Haiman, Christopher A; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E; Couch, Fergus J; Forman, Judith L; Giles, Graham G; Conti, David V; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske-Hohlfeld, Irene; Hicks, Belynda D; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline; Soucy, Penny; Manz, Judith; Cunningham, Julie M; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel; Lindström, Sara; Adams, Marcia; McKay, James D; Phelan, Catherine M; Benlloch, Sara; Kelemen, Linda E; Brennan, Paul; Riggan, Marjorie; O'Mara, Tracy A; Shen, Hongbing; Shi, Yongyong; Thompson, Deborah J; Goodman, Marc T; Nielsen, Sune F; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L; Shelford, Tameka; Edlund, Christopher K; Taylor, Jack A; Field, John K; Park, Sue K; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J; Marchini, Jonathan; Amin Al Olama, Ali; Peters, Ulrike; Eeles, Rosalind A; Seldin, Michael F; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C; Pharoah, Paul D P; Chenevix-Trench, Georgia; Chanock, Stephen J; Simard, Jacques; Easton, Douglas F

2017-01-01

Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures. Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126-35. ©2016 AACR. ©2016 American Association for Cancer Research.

Study Sheds Light on Role of Inherited Mutations in Childhood Cancer

Cancer.gov

In the most comprehensive study of its kind conducted to date, more than 8 percent of children with cancer were found to have inherited genetic mutations associated with a predisposition to the disease.

Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin

PubMed Central

Direk, Nese; Lewis, John G.; Hammond, Geoffrey L.; Hill, Lesley A.; Anderson, Anna; Huffman, Jennifer; Wilson, James F.; Campbell, Harry; Rudan, Igor; Wright, Alan; Hastie, Nicholas; Wild, Sarah H.; Velders, Fleur P.; Hofman, Albert; Uitterlinden, Andre G.; Lahti, Jari; Räikkönen, Katri; Kajantie, Eero; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G.; Kaakinen, Marika; Järvelin, Marjo-Riitta; Timpson, Nicholas J.; Davey Smith, George; Ring, Susan M.; Evans, David M.; St Pourcain, Beate; Tanaka, Toshiko; Milaneschi, Yuri; Bandinelli, Stefania; Ferrucci, Luigi; van der Harst, Pim; Rosmalen, Judith G. M.; Bakker, Stephen J. L.; Verweij, Niek; Dullaart, Robin P. F.; Mahajan, Anubha; Lindgren, Cecilia M.; Morris, Andrew; Lind, Lars; Ingelsson, Erik; Anderson, Laura N.; Pennell, Craig E.; Lye, Stephen J.; Matthews, Stephen G.; Eriksson, Joel; Mellstrom, Dan; Ohlsson, Claes; Price, Jackie F.; Strachan, Mark W. J.; Reynolds, Rebecca M.; Tiemeier, Henning; Walker, Brian R.

2014-01-01

Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30–60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases. PMID:25010111

A mitotically inheritable unit containing a MAP kinase module

PubMed Central

Kicka, Sébastien; Bonnet, Crystel; Sobering, Andrew K.; Ganesan, Latha P.; Silar, Philippe

2006-01-01

Prions are novel kinds of hereditary units, relying solely on proteins, that are infectious and inherited in a non-Mendelian fashion. To date, they are either based on autocatalytic modification of a 3D conformation or on autocatalytic cleavage. Here, we provide further evidence that in the filamentous fungus Podospora anserina, a MAP kinase cascade is probably able to self-activate and generate C, a hereditary unit that bears many similarities to prions and triggers cell degeneration. We show that in addition to the MAPKKK gene, both the MAPKK and MAPK genes are necessary for the propagation of C, and that overexpression of MAPK as that of MAPKKK facilitates the appearance of C. We also show that a correlation exists between the presence of C and localization of the MAPK inside nuclei. These data emphasize the resemblance between prions and a self-positively regulated cascade in terms of their transmission. This thus further expands the concept of protein-base inheritance to regulatory networks that have the ability to self-activate. PMID:16938837

A mitotically inheritable unit containing a MAP kinase module.

PubMed

Kicka, Sébastien; Bonnet, Crystel; Sobering, Andrew K; Ganesan, Latha P; Silar, Philippe

2006-09-05

Prions are novel kinds of hereditary units, relying solely on proteins, that are infectious and inherited in a non-Mendelian fashion. To date, they are either based on autocatalytic modification of a 3D conformation or on autocatalytic cleavage. Here, we provide further evidence that in the filamentous fungus Podospora anserina, a MAP kinase cascade is probably able to self-activate and generate C, a hereditary unit that bears many similarities to prions and triggers cell degeneration. We show that in addition to the MAPKKK gene, both the MAPKK and MAPK genes are necessary for the propagation of C, and that overexpression of MAPK as that of MAPKKK facilitates the appearance of C. We also show that a correlation exists between the presence of C and localization of the MAPK inside nuclei. These data emphasize the resemblance between prions and a self-positively regulated cascade in terms of their transmission. This thus further expands the concept of protein-base inheritance to regulatory networks that have the ability to self-activate.

Ugene, a newly identified protein that is commonly over-expressed in cancer, and that binds uracil DNA-glycosylase

PubMed Central

Guo, Chunguang; Zhang, Xiaodong; Fink, Stephen P; Platzer, Petra; Wilson, Keith; Willson, James K. V.; Wang, Zhenghe; Markowitz, Sanford D

2008-01-01

Expression microarrays identified a novel transcript, designated as Ugene, whose expression is absent in normal colon and colon adenomas, but that is commonly induced in malignant colon cancers. These findings were validated by real-time PCR and Northern blot analysis in an independent panel of colon cancer cases. In addition, Ugene expression was found to be elevated in many other common cancer types, including, breast, lung, uterus, and ovary. Immunofluorescence of V5-tagged Ugene revealed it to have a nuclear localization. In a pull-down assay, uracil DNA-glycosylase 2 (UNG2), an important enzyme in the base excision repair pathway, was identified as a partner protein that binds to Ugene. Co-immunoprecipitation and Western blot analysis confirmed the binding between the endogenous Ugene and UNG2 proteins. Using deletion constructs, we find that Ugene binds to the first 25 amino acids of the UNG2 NH2-terminus. We suggest Ugene induction in cancer may contribute to the cancer phenotype by interacting with the base excision repair pathway. PMID:18676834

Are There Inherited Behavioral Traits that Predispose to Substance Abuse?

ERIC Educational Resources Information Center

Tarter, Ralph E.

1988-01-01

Research suggests predisposition toward alcoholism and drug abuse by inherited behavioral propensities or temperaments which, through interaction with the physical and social environments, shape the development of the personality. Certain personality characteristics, specifically antisocial and neurotic traits, are also linked with the risk for…

Assisted reproduction treatment and epigenetic inheritance

PubMed Central

van Montfoort, A.P.A.; Hanssen, L.L.P.; de Sutter, P.; Viville, S.; Geraedts, J.P.M.; de Boer, P.

2012-01-01

BACKGROUND The subject of epigenetic risk of assisted reproduction treatment (ART), initiated by reports on an increase of children with the Beckwith–Wiedemann imprinting disorder, is very topical. Hence, there is a growing literature, including mouse studies. METHODS In order to gain information on transgenerational epigenetic inheritance and epigenetic effects induced by ART, literature databases were searched for papers on this topic using relevant keywords. RESULTS At the level of genomic imprinting involving CpG methylation, ART-induced epigenetic defects are convincingly observed in mice, especially for placenta, and seem more frequent than in humans. Data generally provide a warning as to the use of ovulation induction and in vitro culture. In human sperm from compromised spermatogenesis, sequence-specific DNA hypomethylation is observed repeatedly. Transmittance of sperm and oocyte DNA methylation defects is possible but, as deduced from the limited data available, largely prevented by selection of gametes for ART and/or non-viability of the resulting embryos. Some evidence indicates that subfertility itself is a risk factor for imprinting diseases. As in mouse, physiological effects from ART are observed in humans. In the human, indications for a broader target for changes in CpG methylation than imprinted DNA sequences alone have been found. In the mouse, a broader range of CpG sequences has not yet been studied. Also, a multigeneration study of systematic ART on epigenetic parameters is lacking. CONCLUSIONS The field of epigenetic inheritance within the lifespan of an individual and between generations (via mitosis and meiosis, respectively) is growing, driven by the expansion of chromatin research. ART can induce epigenetic variation that might be transmitted to the next generation. PMID:22267841

Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women.

PubMed

Rebbeck, Timothy R; Friebel, Tara M; Mitra, Nandita; Wan, Fei; Chen, Stephanie; Andrulis, Irene L; Apostolou, Paraskevi; Arnold, Norbert; Arun, Banu K; Barrowdale, Daniel; Benitez, Javier; Berger, Raanan; Berthet, Pascaline; Borg, Ake; Buys, Saundra S; Caldes, Trinidad; Carter, Jonathan; Chiquette, Jocelyne; Claes, Kathleen B M; Couch, Fergus J; Cybulski, Cezary; Daly, Mary B; de la Hoya, Miguel; Diez, Orland; Domchek, Susan M; Nathanson, Katherine L; Durda, Katarzyna; Ellis, Steve; Evans, D Gareth; Foretova, Lenka; Friedman, Eitan; Frost, Debra; Ganz, Patricia A; Garber, Judy; Glendon, Gord; Godwin, Andrew K; Greene, Mark H; Gronwald, Jacek; Hahnen, Eric; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; John, Esther M; Karlan, Beth Y; Kaufman, Bella; Investigators, KConFab; Kwong, Ava; Laitman, Yael; Lasset, Christine; Lazaro, Conxi; Lester, Jenny; Loman, Niklas; Lubinski, Jan; Manoukian, Siranoush; Mitchell, Gillian; Montagna, Marco; Neuhausen, Susan L; Nevanlinna, Heli; Niederacher, Dieter; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Park, Sue Kyung; Piedmonte, Marion; Radice, Paolo; Rappaport-Fuerhauser, Christine; Rookus, Matti A; Seynaeve, Caroline; Simard, Jacques; Singer, Christian F; Soucy, Penny; Southey, Melissa; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Szabo, Csilla I; Tancredi, Mariella; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda Ewart; Toloczko-Grabarek, Aleksandra; Tung, Nadine; van Rensburg, Elizabeth J; Villano, Danylo; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weitzel, Jeffrey N; Zidan, Jamal; Zorn, Kristin K; McGuffog, Lesley; Easton, Douglas; Chenevix-Trench, Georgia; Antoniou, Antonis C; Ramus, Susan J

2016-11-11

Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.

Empirical data on 220 families with de novo or inherited paracentric inversions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eyre, J.; McConkie-Rosell, A.; Tripp, T.

Six new cases of paracentric inversions (3 detected prenatally) are presented and added to an expanding database of paracentric inversions. Three inversions were associated with an abnormal phenotype and detected postnatally: inv(2)(p21p23), inv(13)(q14q34), and inv(18)(q12.3q23). The present database of paracentric inversions includes 220 families reported. All chromosomes were involved except chromosome 20. The most frequent inversions were found on chromosomes 1, 3, 7, 11, and 14. 48 index cases had an abnormal phenotype not explainable by other causes such as additional chromosome abnormalities. Of these, 12 were de novo and 36 familial. By contrast, of the 122 index cases withmore » normal phenotype, there were 8 de novo and 87 familial cases (rest unknown). Ascertainment bias probably accounts for some of the abnormal inherited inversions cases. Maternally inherited inversions were more frequent than paternally inherited (72 versus 55). Inversions were found in males more than females (ratio of 4 to 3). There were some paracentric inversions that appear to be less involved with abnormal phenotypes (e.g., 11q21q23) than other inversions (e.g., inv X and Turner syndrome). An interesting observation which warrants further investigation is the excess number of fetal losses and karyotypically abnormal progeny in paracentric inversion carriers. The presence of additional karyotypic abnormalities in the children might be explainable by interchromosomal effects and chromosome position changes in the nucleus. Genetic counseling for paracentric inversions should take into consideration mode of ascertainment, inheritance, and chromosome involved. We solicit other cases of paracentric inversions to make this database more useful in counseling patients and families.« less

Dormancy-specific imprinting underlies maternal inheritance of seed dormancy in Arabidopsis thaliana

PubMed Central

Piskurewicz, Urszula; Iwasaki, Mayumi; Susaki, Daichi; Megies, Christian; Kinoshita, Tetsu; Lopez-Molina, Luis

2016-01-01

Mature seed dormancy is a vital plant trait that prevents germination out of season. In Arabidopsis, the trait can be maternally regulated but the underlying mechanisms sustaining this regulation, its general occurrence and its biological significance among accessions are poorly understood. Upon seed imbibition, the endosperm is essential to repress the germination of dormant seeds. Investigation of genomic imprinting in the mature seed endosperm led us to identify a novel set of imprinted genes that are expressed upon seed imbibition. Remarkably, programs of imprinted gene expression are adapted according to the dormancy status of the seed. We provide direct evidence that imprinted genes play a role in regulating germination processes and that preferential maternal allelic expression can implement maternal inheritance of seed dormancy levels. DOI: http://dx.doi.org/10.7554/eLife.19573.001 PMID:28005006

Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010).

PubMed

Bellumori, Thomas P; Famula, Thomas R; Bannasch, Danika L; Belanger, Janelle M; Oberbauer, Anita M

2013-06-01

To determine the proportion of mixed-breed and purebred dogs with common genetic disorders. Case-control study. 27,254 dogs with an inherited disorder. Electronic medical records were reviewed for 24 genetic disorders: hemangiosarcoma, lymphoma, mast cell tumor, osteosarcoma, aortic stenosis, dilated cardiomyopathy, hypertrophic cardiomyopathy, mitral valve dysplasia, patent ductus arteriosus, ventricular septal defect, hyperadrenocorticism, hypoadrenocorticism, hypothyroidism, elbow dysplasia, hip dysplasia, intervertebral disk disease, patellar luxation, ruptured cranial cruciate ligament, atopy or allergic dermatitis, bloat, cataracts, epilepsy, lens luxation, and portosystemic shunt. For each disorder, healthy controls matched for age, body weight, and sex to each affected dog were identified. Genetic disorders differed in expression. No differences in expression of 13 genetic disorders were detected between purebred dogs and mixed-breed dogs (ie, hip dysplasia, hypo- and hyperadrenocorticism, cancers, lens luxation, and patellar luxation). Purebred dogs were more likely to have 10 genetic disorders, including dilated cardiomyopathy, elbow dysplasia, cataracts, and hypothyroidism. Mixed-breed dogs had a greater probability of ruptured cranial cruciate ligament. Prevalence of genetic disorders in both populations was related to the specific disorder. Recently derived breeds or those from similar lineages appeared to be more susceptible to certain disorders that affect all closely related purebred dogs, whereas disorders with equal prevalence in the 2 populations suggested that those disorders represented more ancient mutations that are widely spread through the dog population. Results provided insight on how breeding practices may reduce prevalence of a disorder.

Deep dermatophytosis and inherited CARD9 deficiency.

PubMed

Lanternier, Fanny; Pathan, Saad; Vincent, Quentin B; Liu, Luyan; Cypowyj, Sophie; Prando, Carolina; Migaud, Mélanie; Taibi, Lynda; Ammar-Khodja, Aomar; Stambouli, Omar Boudghene; Guellil, Boumediene; Jacobs, Frederique; Goffard, Jean-Christophe; Schepers, Kinda; Del Marmol, Véronique; Boussofara, Lobna; Denguezli, Mohamed; Larif, Molka; Bachelez, Hervé; Michel, Laurence; Lefranc, Gérard; Hay, Rod; Jouvion, Gregory; Chretien, Fabrice; Fraitag, Sylvie; Bougnoux, Marie-Elisabeth; Boudia, Merad; Abel, Laurent; Lortholary, Olivier; Casanova, Jean-Laurent; Picard, Capucine; Grimbacher, Bodo; Puel, Anne

2013-10-31

Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.).

From Phenotype to Genotype: Exploring Middle School Students' Understanding of Genetic Inheritance in a Web-Based Environment

ERIC Educational Resources Information Center

Williams, Michelle; Montgomery, Beronda L.; Manokore, Viola

2012-01-01

Research shows that students face challenges as they learn about genetic inheritance. The challenges could emanate from the fact that genetic inheritance involves unseen processes at different organizational levels. We explored students' understanding of heredity and related concepts such as cells and reproduction using a Web-based Science Inquiry…

[Application of targeted capture technology and next generation sequencing in molecular diagnosis of inherited myopathy].

PubMed

Fu, Xiaona; Liu, Aijie; Yang, Haipo; Wei, Cuijie; Ding, Juan; Wang, Shuang; Wang, Jingmin; Yuan, Yun; Jiang, Yuwu; Xiong, Hui

2015-10-01

To elucidate the usefulness of next generation sequencing for diagnosis of inherited myopathy, and to analyze the relevance between clinical phenotype and genotype in inherited myopathy. Related genes were selected for SureSelect target enrichment system kit (Panel Version 1 and Panel Version 2). A total of 134 patients who were diagnosed as inherited myopathy clinically underwent next generation sequencing in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2014. Clinical information and gene detection result of the patients were collected and analyzed. Seventy-seven of 134 patients (89 males and 45 females, visiting ages from 6-month-old to 26-year-old, average visiting age was 6 years and 1 month) underwent next generation sequencing by Panel Version 1 in 2013, and 57 patients underwent next generation sequencing by Panel Version 2 in 2014. The gene detection revealed that 74 patients had pathogenic gene mutations, and the positive rate of genetic diagnosis was 55.22%. One patient was diagnosed as metabolic myopathy. Five patients were diagnosed as congenital myopathy; 68 were diagnosed as muscular dystrophy, including 22 with congenital muscular dystrophy 1A (MDC1A), 11 with Ullrich congenital muscular dystrophy (UCMD), 6 with Bethlem myopathy (BM), 12 with Duchenne muscular dystrophy (DMD) caused by point mutations in DMD gene, 5 with LMNA-related congenital muscular dystrophy (L-CMD), 1 with Emery-Dreifuss muscular dystrophy (EDMD), 7 with alpha-dystroglycanopathy (α-DG) patients, and 4 with limb-girdle muscular dystrophy (LGMD) patients. Next generation sequencing plays an important role in diagnosis of inherited myopathy. Clinical and biological information analysis was essential for screening pathogenic gene of inherited myopathy.

Identification of novel mutations including a double mutation in patients with inherited cardiomyopathy by a targeted sequencing approach using the Ion Torrent PGM system.

PubMed

Zhao, Yue; Cao, Hong; Song, Yindi; Feng, Yue; Ding, Xiaoxue; Pang, Mingjie; Zhang, Yunmei; Zhang, Hong; Ding, Jiahuan; Xia, Xueshan

2016-06-01

Inherited cardiomyopathy is the major cause of sudden cardiac death (SCD) and heart failure (HF). The disease is associated with extensive genetic heterogeneity; pathogenic mutations in cardiac sarcomere protein genes, cytoskeletal protein genes and nuclear envelope protein genes have been linked to its etiology. Early diagnosis is conducive to clinical monitoring and allows for presymptomatic interventions as needed. In the present study, the entire coding sequences and flanking regions of 12 major disease (cardiomyopathy)-related genes [namely myosin, heavy chain 7, cardiac muscle, β (MYH7); myosin binding protein C, cardiac (MYBPC3); lamin A/C (LMNA); troponin I type 3 (cardiac) (TNNI3); troponin T type 2 (cardiac) (TNNT2); actin, α, cardiac muscle 1 (ACTC1); tropomyosin 1 (α) (TPM1); sodium channel, voltage gated, type V alpha subunit (SCN5A); myosin, light chain 2, regulatory, cardiac, slow (MYL2); myosin, heavy chain 6, cardiac muscle, α (MYH6); myosin, light chain 3, alkali, ventricular, skeletal, slow (MYL3); and protein kinase, AMP-activated, gamma 2 non-catalytic subunit  (PRKAG2)] in 8 patients with dilated cardiomyopathy (DCM) and in 8 patients with hypertrophic cardiomyopathy (HCM) were amplified and then sequenced using the Ion Torrent Personal Genome Machine (PGM) system. As a result, a novel heterozygous mutation (MYH7, p.Asn885Thr) and a variant of uncertain significance (TNNT2, p.Arg296His) were identified in 2 patients with HCM. These 2 missense mutations, which were absent in the samples obtained from the 200 healthy control subjects, altered the amino acid that was evolutionarily conserved among a number of vertebrate species; this illustrates that these 2 non-synonymous mutations play a role in the pathogenesis of HCM. Moreover, a double heterozygous mutation (PRKAG2, p.Gly100Ser plus MYH7, p.Arg719Trp) was identified in a patient with severe familial HCM, for the first time to the best of our

[Analysis of clinical phenotype and mode of inheritance in retinitis pigmentosa patients with consanguineous marriage].

PubMed

Rong, Wei-ning; Sheng, Xun-lun; Liu, Ya-ni

2012-10-01

To analyse the mode of inheritance and clinical characteristics of retinitis pigmentosa (RP) patients with consanguineous marriage. RP patients were recruited for this study in Ningxia Eye Hospital from September 2009 to July 2011. All patients received complete ophthalmic examination. The mode of inheritance were determined based on family history and marriage history. Clinical features were characterized by complete ophthalmic examinations including visual acuity, macular OCT, visual field and electroretinogram (ERG). A total of 143 individuals with RP (33 families) were recruited. Based on analysis of family history and marriage history, 20 RP families (23 patients) had consanguineous marriage history accounted for 60.6% RP families (16.1% RP patients). There were 4 patients (from 4 families) diagnosed as Usher syndrome. In 20 RP families with consanguineous marriage history, 7 families (35.0%) were Hui ethnicity and 13 families (65%) were Han ethnicity. The marriages of 15 families were between first cousins and 3 families were between second cousins, only 2 families were between half cousins matrimony. Of 23 RP patients, 12 were males and 11 were females. The average age of onset was 11.4 ± 6.8 years and the average age of recruitment was (32.0 ± 13.5) years. The best-corrected visual acuity was less than 0.6 in 78.2% patients. According to the features of the fundus, 13 patients were classical retinitis pigmentosa and 10 patients were retinitis pigmentosa sine pigmento. Visual field examination showed that all patients had varying degrees of peripheral visual field defect. Retinal neuroepithelial layer of macular and peripheral retina became thinner and retinal photoreceptors were disappeared. The average thickness of macular fovea was (186.1 ± 78.7) µm on right eyes and (187.4 ± 76.3) µm on left eyes. The incidence of RP with consanguineous marriages was high in Ningxia Region. The mode of inheritance of RP patients with consanguinity is autosomal

Inherited tertiary hypothyroidism in Sprague-Dawley rats.

PubMed

Stoica, George; Lungu, Gina; Xie, Xueyi; Abbott, Louise C; Stoica, Heidi M; Jaques, John T

2007-05-07

Thyroid hormones (THs) are important in the development and maturation of the central nervous system (CNS). The significant actions of THs during CNS development occur at the time when TH levels are lower than those in the mother and the hypothalamic-thyroid (HPT) axis is not fully functional. In the developing rat nervous system, primarily the cerebellum, the first three postnatal weeks represent a period of significant sensitivity to thyroid hormones. This study presents a spontaneous, inherited recessive hypothyroidism in Sprague-Dawley rats with devastating functional consequences to the development of the CNS. The clinical signs develop around 14 day's postnatal (dpn) and are characterized by ataxia, spasticity, weight loss and hypercholesterolemia. The afflicted rats died at 30 days due to severe neurological deficits. The deterioration affects the entire CNS and is characterized by progressive neuronal morphological and biochemical changes, demyelination and astrogliosis. The cerebellum, brain stem, neocortex, hippocampus and adrenal gland medulla appear to be most affected. Thyroid Stimulating Hormone (TSH), T3 and T4 levels were significantly lower in hypothyroid rats than control. Immunohistochemistry and RT-PCR demonstrated a reduction of Thyrotropin Releasing Hormone (TRH) in the hypothalamus of hypothyroid rats. The weight of both thyroid and pituitary glands were significantly less in hypothyroid rats than the corresponding normal littermate controls. Transmission electron microscopy demonstrates consistent postsynaptic dendritic, synaptic and spine alterative changes in the brain of hypothyroid rats. These data suggest that we discovered a tertiary form of inherited hypothyroidism involving the hypothalamus.

Inheritance and mechanism of resistance to herbicides inhibiting acetolactate synthase in Sonchus oleraceus L.

PubMed

Boutsalis, P; Powles, S B

1995-07-01

A biotype of Sonchus oleraceus L. (Compositae) has developed resistance to herbicides inhibiting acetolactate synthase (ALS) following field selection with chlorsulfuron for 8 consecutive years. The aim of this study was to determine the inheritance and mechanism of resistance in this biotype. Determination of ALS activity and inhibition kinetics revealed that Km and Vmax did not vary greatly between the resistant and susceptible biotypes. ALS extracted from the resistant biotype was resistant to five ALS-inhibiting herbicides in an in vitro assay. ALS activity from the resistant biotype was 14 19, 2, 3 and 3 times more resistant to inhibition by chlorsulfuron, sulfometuron, imazethapyr, imazapyr and flumetsulam, respectively, than the susceptible biotype. Hybrids between the resistant and a susceptible biotype were produced, and inheritance was followed through the F1, F2 and F3 generations. F1 hybrids displayed a uniform intermediate level of resistance between resistant and susceptible parents. Three distinct phenotypes, resistant, intermediate and susceptible, were identified in the F2 generation following chlorsulfuron application. A segregation ratio of 1∶2∶1 was observed, indicative of the action of a single, nuclear, incompletely dominant gene. F3 families, derived from intermediate F2 individuals, segregated in a similar manner. Resistance to herbicides inhibiting ALS in this biotype of S. oleraceus is due to the effect of a single gene coding for a resistant form of the target enzyme, ALS.

Common breast cancer risk variants in the post-COGS era: a comprehensive review.

PubMed

Maxwell, Kara N; Nathanson, Katherine L

2013-12-20

Breast cancer has a strong heritable component, with approximately 15% of cases exhibiting a family history of the disease. Mutations in genes such as BRCA1, BRCA2 and TP53 lead to autosomal dominant inherited cancer susceptibility and confer a high lifetime risk of breast cancers. Identification of mutations in these genes through clinical genetic testing enables patients to undergo screening and prevention strategies, some of which provide overall survival benefit. In addition, a number of mutant alleles have been identified in genes such as CHEK2, PALB2, ATM and BRIP1, which often display incomplete penetrance and confer moderate lifetime risks of breast cancer. Studies are underway to determine how to use the identification of mutations in these genes to guide clinical practice. Altogether, however, mutations in high and moderate penetrance genes probably account for approximately 25% of familial breast cancer risk; the remainder may be due to mutations in as yet unidentified genes or lower penetrance variants. Common low penetrance alleles, which have been mainly identified through genome-wide association studies (GWAS), are generally present at 10 to 50% population frequencies and confer less than 1.5-fold increases in breast cancer risk. A number of single nucleotide polymorphisms (SNPs) have been identified and risk associations extensively replicated in populations of European ancestry, the number of which has substantially increased as a result of GWAS performed by the Collaborative Oncological Gene-environment Study consortium. It is now estimated that 28% of familial breast cancer risk is explained by common breast cancer susceptibility loci. In some cases, SNP associations may be specific to different subsets of women with breast cancer, as defined by ethnicity or estrogen receptor status. Although not yet clinically established, it is hoped that identification of common risk variants may eventually allow identification of women at higher risk of

Common breast cancer risk variants in the post-COGS era: a comprehensive review

PubMed Central

2013-01-01

Breast cancer has a strong heritable component, with approximately 15% of cases exhibiting a family history of the disease. Mutations in genes such as BRCA1, BRCA2 and TP53 lead to autosomal dominant inherited cancer susceptibility and confer a high lifetime risk of breast cancers. Identification of mutations in these genes through clinical genetic testing enables patients to undergo screening and prevention strategies, some of which provide overall survival benefit. In addition, a number of mutant alleles have been identified in genes such as CHEK2, PALB2, ATM and BRIP1, which often display incomplete penetrance and confer moderate lifetime risks of breast cancer. Studies are underway to determine how to use the identification of mutations in these genes to guide clinical practice. Altogether, however, mutations in high and moderate penetrance genes probably account for approximately 25% of familial breast cancer risk; the remainder may be due to mutations in as yet unidentified genes or lower penetrance variants. Common low penetrance alleles, which have been mainly identified through genome-wide association studies (GWAS), are generally present at 10 to 50% population frequencies and confer less than 1.5-fold increases in breast cancer risk. A number of single nucleotide polymorphisms (SNPs) have been identified and risk associations extensively replicated in populations of European ancestry, the number of which has substantially increased as a result of GWAS performed by the Collaborative Oncological Gene–environment Study consortium. It is now estimated that 28% of familial breast cancer risk is explained by common breast cancer susceptibility loci. In some cases, SNP associations may be specific to different subsets of women with breast cancer, as defined by ethnicity or estrogen receptor status. Although not yet clinically established, it is hoped that identification of common risk variants may eventually allow identification of women at higher risk of

Deconstructing Black Swans: An Introductory Approach to Inherited Metabolic Disorders in the Neonate.

PubMed

Mew, Nicholas Ah; Viall, Sarah; Kirmse, Brian; Chapman, Kimberly A

2015-08-01

Inherited metabolic disorders (IMDs) are individually rare but collectively common disorders that frequently require rapid or urgent therapy. This article provides a generalized approach to IMDs, as well as some investigations and safe therapies that may be initiated pending the metabolic consult. An overview of the research supporting management strategies is provided. In addition, the newborn metabolic screen is reviewed. Caring for infants with IMDs can seem difficult because each of the types is rarely seen; however, collectively the management can be seen as similar. When an IMD is suspected, a metabolic specialist should be consulted for expert advice regarding appropriate laboratory investigations and management. Because rapid intervention of IMDs before the onset of symptoms may prevent future irreversible sequelae, each abnormal newborn screen must be addressed promptly. Management can be difficult. Research in this area is limited and can be difficult without multisite coordination since sample sizes of any significance are difficult to achieve.

Role of immune cells in animal models for inherited neuropathies: facts and visions.

PubMed

Mäurer, Mathias; Kobsar, Igor; Berghoff, Martin; Schmid, Christoph D; Carenini, Stefano; Martini, Rudolf

2002-04-01

Mice heterozygously deficient in the peripheral myelin adhesion molecule P0 (P0+/- mice) are models for some forms of Charcot-Marie-Tooth (CMT) neuropathies. In addition to the characteristic hallmarks of demyelination, elevated numbers of CD8-positive T-lymphocytes and F4/80-positive macrophages are striking features in the nerves of these mice. These immune cells increase in number with age and progress of demyelination, suggesting that they might be functionally related to myelin damage. In order to investigate the pathogenetic role of lymphocytes, the myelin mutants were cross-bred with recombination activating gene 1 (RAG-1)-deficient mice, which lack mature T- and B-lymphocytes. The immunodeficient myelin mutants showed a less severe myelin degeneration. The beneficial effect of lymphocyte-deficiency was reversible, since demyelination worsened in immunodeficient myelin-mutants when reconstituted with bone marrow from wild-type mice. Ultrastructural analysis revealed macrophages in close apposition to myelin and demyelinated axons. We therefore cross-bred the P0+/- mice with spontaneous osteopetrotic (op) mutants deficient in the macrophage colony-stimulating factor (M-CSF), hence displaying impaired macrophage activation. In the corresponding double mutants the numbers of macrophages were not elevated in the peripheral nerves, and the demyelinating phenotype was less severe than in the genuine P0+/- mice, demonstrating that macrophages are also functionally involved in the pathogenesis of genetically mediated demyelination. We also examined other models for inherited neuropathies for a possible involvement of immune cells. We chose mice deficient in the gap junction component connexin 32, a model for the X-linked form of CMT. Similar to P0-deficient mice, T-lymphocytes and macrophages were elevated and macrophages showed a close apposition to degenerating myelin. We conclude that the involvement of T-lymphocytes and macrophages is a common pathogenetic

Autosomal dominant inheritance of Brachmann-de Lange syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozma, C.

A mother with mild phenotype and her severely affected son, both with classic manifestations of Brachmann-de Lange syndrome (BDLS), are described. This documented mother-to-child transmission supports the hypothesis of autosomal dominant transmission with intrafamilial variability. Known cases of BDLS with autosomal dominant inheritance are reviewed. Although most cases of BDLS are sporadic, a careful evaluation of parents of affected children is important for appropriate genetic counseling. 15 refs., 3 figs., 1 tab.

Inheritance and heritability of deltamethrin resistance under laboratory conditions of Triatoma infestans from Bolivia.

PubMed

Gomez, Marinely Bustamante; Pessoa, Grasielle D'Avila Caldas; Rosa, Aline Cristine Luiz; Echeverria, Jorge Espinoza; Diotaiuti, Liléia Gonçalves

2015-11-16

Over the last few decades, pyrethroid-resistant in Triatoma infestans populations have been reported, mainly on the border between Argentina and Bolivia. Understanding the genetic basis of inheritance mode and heritability of resistance to insecticides under laboratory conditions is crucial for vector management and monitoring of insecticide resistance. Currently, few studies have been performed to characterize the inheritance mode of resistance to pyrethroids in T. infestans; for this reason, the present study aims to characterize the inheritance and heritability of deltamethrin resistance in T. infestans populations from Bolivia with different toxicological profiles. Experimental crosses were performed between a susceptible (S) colony and resistant (R) and reduced susceptibility (RS) colonies in both directions (♀ x ♂ and ♂ x ♀), and inheritance mode was determined based on degree of dominance (DO) and effective dominance (D(ML)). In addition, realized heritability (h(2)) was estimated based on a resistant colony, and select pressure was performed for two generations based on the diagnostic dose (10 ng. i. a. /nymph). The F1 progeny of the experimental crosses and the selection were tested by a standard insecticide resistance bioassay. The result for DO and D(ML) (< 1) indicates that resistance is an incompletely dominant character, and inheritance is autosomal, not sex-linked. The LD50 for F1 of ♀S x ♂R and ♂S x ♀R was 0.74 and 3.97, respectively, which is indicative of dilution effect. In the resistant colony, after selection pressure, the value of h(2) was 0.37; thus, the LD50 value increased 2.25-fold (F2) and 26.83-fold (F3) compared with the parental colony. The inheritance mode of resistance of T. infestans to deltamethrin, is autosomal and an incompletely dominant character; this is a previously known process, confirmed in the present study on T. infestans populations from Bolivia. The lethal doses (LD50) increase from one generation to

Lack of Association between Recurrent Pregnancy Loss and Inherited Thrombophilia in a Group of Colombian Patients

PubMed Central

Cardona, Henry; Castañeda, Serguei A.; Cardona Maya, Wálter; Alvarez, Leonor; Gómez, Joaquín; Gómez, Jorge; Torres, José; Tobón, Luis; Bedoya, Gabriel; Cadavid, Ángela P.

2012-01-01

Studies have shown an association between recurrent pregnancy loss and inherited thrombophilia in Caucasian populations, but there is insufficient knowledge concerning triethnic populations such as the Colombian. The aim of this study was to evaluate whether inherited thrombophilia is associated with recurrent pregnancy loss. Methods. We conducted a case-control study of 93 patients with recurrent pregnancy loss (cases) and 206 healthy multiparous women (controls) in a Colombian subpopulation. Three single nucleotide polymorphisms (SNPs) markers of the inherited thrombophilias factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T were genotyped by PCR-RFLP. Activated protein C resistance and plasma levels of antithrombin, protein C, and protein S were also measured. Results. The frequency of thrombophilia-associated SNPs, activated protein C resistance, and anticoagulant protein deficiencies, was low overall, except for the methylenetetrahydrofolate reductase C677T SNP. The differences between patients and controls had no statistical significance. Conclusion. Our study confirms the low prevalence of inherited thrombophilias in non-Caucasian populations and it is unlikely that the tested thrombophilias play a role in the pathogenesis of recurrent pregnancy loss in this Colombian population. PMID:22577540

Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

PubMed Central

Rietveld, Cornelius A.; Esko, Tõnu; Davies, Gail; Pers, Tune H.; Turley, Patrick; Benyamin, Beben; Chabris, Christopher F.; Emilsson, Valur; Johnson, Andrew D.; Lee, James J.; de Leeuw, Christiaan; Marioni, Riccardo E.; Medland, Sarah E.; Miller, Michael B.; Rostapshova, Olga; van der Lee, Sven J.; Vinkhuyzen, Anna A. E.; Amin, Najaf; Conley, Dalton; Derringer, Jaime; van Duijn, Cornelia M.; Fehrmann, Rudolf; Franke, Lude; Glaeser, Edward L.; Hansell, Narelle K.; Hayward, Caroline; Iacono, William G.; Ibrahim-Verbaas, Carla; Jaddoe, Vincent; Karjalainen, Juha; Laibson, David; Lichtenstein, Paul; Liewald, David C.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; McMahon, George; Pedersen, Nancy L.; Pinker, Steven; Porteous, David J.; Posthuma, Danielle; Rivadeneira, Fernando; Smith, Blair H.; Starr, John M.; Tiemeier, Henning; Timpson, Nicholas J.; Trzaskowski, Maciej; Uitterlinden, André G.; Verhulst, Frank C.; Ward, Mary E.; Wright, Margaret J.; Davey Smith, George; Deary, Ian J.; Johannesson, Magnus; Plomin, Robert; Visscher, Peter M.; Benjamin, Daniel J.; Koellinger, Philipp D.

2014-01-01

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory. PMID:25201988

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population.

PubMed

Kourtian, Silva; Soueid, Jihane; Makhoul, Nadine J; Guisso, Dikran Richard; Chahrour, Maria; Boustany, Rose-Mary N

2017-03-30

Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ 2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype.

Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

PubMed Central

Kourtian, Silva; Soueid, Jihane; Makhoul, Nadine J.; Guisso, Dikran Richard; Chahrour, Maria; Boustany, Rose-Mary N.

2017-01-01

Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype. PMID:28358038

Familial exudative vitreoretinopathy: A report of an asymptomatic case with autosomal dominant inheritance detected using FZD4 molecular analysis.

PubMed

Montecinos-Contreras, C; Sepúlveda-Vázquez, H E; Pelcastre-Luna, E; Zenteno, J C; Villanueva-Mendoza, C

2017-04-01

To report a familial case of Familial Exudative Vitreoretinopathy (FEVR) with an autosomal dominant inheritance pattern identified with the molecular analysis of FZD4. The proband is a 13 year-old boy who consulted for low vision. Fundus examination revealed a peripheral avascular zone and macular dragging, consistent with FEVR. Molecular analysis demonstrated a mutation of FZD4 in DNA from both the patient and his asymptomatic mother. This familial case was identified with the molecular analysis of FZD4 and shows the importance to explore first degree relatives in a sporadic FEVR case. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Gene therapy for inherited retinal and optic nerve degenerations.

PubMed

Moore, Nicholas A; Morral, Nuria; Ciulla, Thomas A; Bracha, Peter

2018-01-01

The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity. Areas covered: This review covers Leber's congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber's hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis. Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype.

Who's your daddy?: paternal inheritance of metabolic disease risk.

PubMed

Isganaitis, Elvira; Suehiro, Harumi; Cardona, Connie

2017-02-01

Although the importance of optimizing mothers' health prior to conception and during pregnancy is now well accepted, recent data also implicate health and nutritional status of fathers as contributors to chronic disease risk in their progeny. This brief review will highlight recent epidemiological and experimental studies linking paternal overnutrition, undernutrition, and other forms of stress, to metabolic disease in the offspring. The past 2 years have brought tremendous insights into the mechanisms by which paternal exposures can contribute to disease susceptibility in the next generation. Recent data, both from humans and experimental models, demonstrate that paternal obesity and undernutrition result in epigenetic reprogramming of male germ cells, notably altered DNA methylation, histone retention, and expression of small noncoding RNAs and transfer RNA fragments. Novel mechanisms have also been identified, such as epididymal transport vesicles, seminal fluid hormones and metabolites, and a unique seminal fluid microbiome. Paternal nutritional and other perturbations are linked to risk of metabolic disease and obesity in offspring. Germ cell-dependent mechanisms have recently been linked to these intergenerational effects. Nongenetic, paternal inheritance of chronic disease has important implications for public health, and may provide novel opportunities for multigenerational disease prevention.

Gene therapy for inherited muscle diseases: where genetics meets rehabilitation medicine.

PubMed

Braun, Robynne; Wang, Zejing; Mack, David L; Childers, Martin K

2014-11-01

The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed.

Mutation screening of Chinese Treacher Collins syndrome patients identified novel TCOF1 mutations.

PubMed

Chen, Ying; Guo, Luo; Li, Chen-Long; Shan, Jing; Xu, Hai-Song; Li, Jie-Ying; Sun, Shan; Hao, Shao-Juan; Jin, Lei; Chai, Gang; Zhang, Tian-Yu

2018-04-01

Treacher Collins syndrome (TCS) (OMIM 154500) is a rare congenital craniofacial disorder with an autosomal dominant manner of inheritance in most cases. To date, three pathogenic genes (TCOF1, POLR1D and POLR1C) have been identified. In this study, we conducted mutational analysis on Chinese TCS patients to reveal a mutational spectrum of known causative genes and show phenotype-genotype data to provide more information for gene counselling and future studies on the pathogenesis of TCS. Twenty-two TCS patients were recruited from two tertiary referral centres, and Sanger sequencing for the coding exons and exon-intron boundaries of TCOF1, POLR1D and POLR1C was performed. For patients without small variants, further copy number variations (CNVs) analysis was conducted using high-density SNP array platforms. The Sanger sequencing overall mutation detection rate was as high as 86.3% (19/22) for our cohort. Fifteen TCOF1 pathogenic variants, including ten novel mutations, were identified in nineteen patients. No causative mutations in POLR1D and POLR1C genes and no CNVs mutations were detected. A suspected autosomal dominant inheritance case that implies germinal mosaicism was described. Our study confirmed that TCOF1 was the main disease-causing gene for the Chinese TCS population and revealed its mutation spectrum. We also addressed the need for more studies of mosaicism in TCS cases, which could explain the mechanism of autosomal dominant inheritance in TCS cases and benefit the prevention of TCS.

The Yeast Gene, MDM20, Is Necessary for Mitochondrial Inheritance and Organization of the Actin Cytoskeleton

PubMed Central

Hermann, Greg J.; King, Edward J.; Shaw, Janet M.

1997-01-01

In Saccharomyces cerevisiae, the growing bud inherits a portion of the mitochondrial network from the mother cell soon after it emerges. Although this polarized transport of mitochondria is thought to require functions of the cytoskeleton, there are conflicting reports concerning the nature of the cytoskeletal element involved. Here we report the isolation of a yeast mutant, mdm20, in which both mitochondrial inheritance and actin cables (bundles of actin filaments) are disrupted. The MDM20 gene encodes a 93-kD polypeptide with no homology to other characterized proteins. Extra copies of TPM1, a gene encoding the actin filament–binding protein tropomyosin, suppress mitochondrial inheritance defects and partially restore actin cables in mdm20Δ cells. Synthetic lethality is also observed between mdm20 and tpm1 mutant strains. Overexpression of a second yeast tropomyosin, Tpm2p, rescues mutant phenotypes in the mdm20 strain to a lesser extent. Together, these results provide compelling evidence that mitochondrial inheritance in yeast is an actin-mediated process. MDM20 and TPM1 also exhibit the same pattern of genetic interactions; mutations in MDM20 are synthetically lethal with mutations in BEM2 and MYO2 but not SAC6. Although MDM20 and TPM1 are both required for the formation and/or stabilization of actin cables, mutations in these genes disrupt mitochondrial inheritance and nuclear segregation to different extents. Thus, Mdm20p and Tpm1p may act in vivo to establish molecular and functional heterogeneity of the actin cytoskeleton. PMID:9105043

Knowledge, Attitudes, and Beliefs of Arab-American Women Regarding Inherited Cancer Risk

PubMed Central

Gauthier, Jacqueline; Cichon, Michelle; Hammad, Adnan; Simon, Michael S.

2013-01-01

The increasing incidence of breast cancer in the Arab world, coupled with a relatively early age of onset, raises concern for the presence of hereditary risk factors in this population. However, due to potential structural and cultural barriers, Arab Americans make up the smallest percentage of individuals tested for Hereditary Breast and Ovarian Cancer Syndrome in the United States. The objectives of this qualitative pilot focus group of 13 Arab-American women were to explore attitudes, knowledge and beliefs regarding hereditary breast cancer in the Arab-American community in metropolitan Detroit, identify barriers that would prevent women from seeking hereditary cancer screening/testing and determine who women would talk to about inherited cancer. Results indicated that cultural beliefs and personal experiences with cancer influenced the women’s perspectives on hereditary cancer risk. A high level of secrecy about cancer within Arab-American families was present, which may prevent accurate risk assessment and referral for genetic services. Other identified barriers that may influence hereditary risk assessment included stigma, fears and misconceptions of cancer. While these barriers were present, participants also expressed a strong need for education and tailored cancer risk information for their community. PMID:23054337

Knowledge, attitudes, and beliefs of Arab-American women regarding inherited cancer risk.

PubMed

Mellon, Suzanne; Gauthier, Jacqueline; Cichon, Michelle; Hammad, Adnan; Simon, Michael S

2013-04-01

The increasing incidence of breast cancer in the Arab world, coupled with a relatively early age of onset, raises concern for the presence of hereditary risk factors in this population. However, due to potential structural and cultural barriers, Arab Americans make up the smallest percentage of individuals tested for Hereditary Breast and Ovarian Cancer Syndrome in the United States. The objectives of this qualitative pilot focus group of 13 Arab-American women were to explore attitudes, knowledge and beliefs regarding hereditary breast cancer in the Arab-American community in metropolitan Detroit, identify barriers that would prevent women from seeking hereditary cancer screening/testing and determine who women would talk to about inherited cancer. Results indicated that cultural beliefs and personal experiences with cancer influenced the women's perspectives on hereditary cancer risk. A high level of secrecy about cancer within Arab-American families was present, which may prevent accurate risk assessment and referral for genetic services. Other identified barriers that may influence hereditary risk assessment included stigma, fears and misconceptions of cancer. While these barriers were present, participants also expressed a strong need for education and tailored cancer risk information for their community.

End-Stage Kidney Failure in Oman: An Analysis of Registry Data with an Emphasis on Congenital and Inherited Renal Diseases

PubMed Central

Al Mawali, Adhra; Al Maimani, Yacoub

2017-01-01

Globally, end-stage kidney disease (ESKD) is a huge burden on health care systems. The aims of this study were to perform a comprehensive epidemiological and etiological report of ESKD patients commencing RRT in Oman with an emphasis on genetic causes and inherited kidney disease. All newly registered Omani patients with ESKD commencing RRT from 2001 until 2015 (n = 2,922) were analysed using the RRT register in Oman. All potentially genetic or inherited causes of ESKD were reviewed. In Oman, ESKD is more prevalent in males (57.1%) than females (42.9%) with a median age of incident ESKD of 53 years. Diabetic nephropathy was the most prevalent cause of ESKD (46%), followed by hypertensive nephropathy (19%), glomerulonephritis (15%), and inherited kidney disease (5%). For patients less than 20 years of age inherited kidney disease accounted for 32.5% of cases. Of this cohort with inherited renal disease, 40.3% had autosomal dominant polycystic kidney disease, 11.5% had congenital anomalies of the kidney and urinary tract, 9.4% had Alport syndrome, and 7.2% had autosomal recessive polycystic kidney disease. This study represents a comprehensive population-based epidemiological and etiological report of ESKD patients in Oman commencing RRT. Inherited kidney disease was the leading cause of paediatric ESKD. PMID:28685101

A family with spondyloepimetaphyseal dwarfism: a 'new' dysplasia or Kniest disease with autosomal recessive inheritance?

PubMed Central

Farag, T I; Al-Awadi, S A; Hunt, M C; Satyanath, S; Zahran, M; Usha, R; Uma, R

1987-01-01

We present an Arab family with some features of Kniest disease. The proband was a six year old boy with rhizomelic short limbed dwarfism, 'dish-like' facies, cleft palate, deafness, and camptodactyly. Most radiological changes were compatible with Kniest disease. Two younger sibs, similarly affected, had died at a few months old, and the pedigree shows strong evidence of autosomal recessive inheritance, unlike previously reported cases of Kniest disease which have shown autosomal dominant inheritance. Images PMID:3681904

Freud's philosophical inheritance: Schopenhauer and Nietzsche in Beyond the Pleasure Principle.

PubMed

Grimwade, Robert

2012-06-01

This essay explores the possible significance of Freud's references to Schopenhauer and Nietzsche in Beyond the Pleasure Principle. It attempts to reveal two sides of Freud's philosophical inheritance and explores the structure of Freud's ambivalence toward his intellectual predecessors.

The occurrence and suspected mode of inheritance of congenital subaortic stenosis and tricuspid valve dysplasia in Dogue de Bordeaux dogs.

PubMed

Ohad, D G; Avrahami, A; Waner, T; David, L

2013-08-01

The Dogue de Bordeaux (DdB) breed has gone through several genetic 'bottle necks' and has a relatively small effective population size. Importing new stock into Israel has been limited, further narrowing the already restricted local gene-pool and increasing the chances of inherited defects. In 56 DdB dogs examined between 2003 and 2010, the authors sought to study the proportion congenital subaortic stenosis (SAS) and tricuspid valve dysplasia (TVD). The aim was also to identify a probable mode of inheritance (MOI) using segregation and pedigree analyses of genealogical data available from 13/21 DdB dogs diagnosed with these conditions between 2004 and 2007. Among all breeds in the country, TVD was highest in the DdB breed, which also displayed the second highest proportion of SAS. Echocardiographic measurements and selected physical examination findings from 26 normal DdB dogs, 18 DdB dogs with SAS, and 12 DdB dogs with TVD are reported. Based on pedigree and segregation analyses, the most probable MOI appeared to be autosomal recessive. Pedigree analyses helped to identify three ancestors that might have introduced these two congenital heart defects into the local DdB population. Excluding those three dogs and their progeny from future mating could therefore reduce the prevalence of these diseases in the DdB population in Israel. The unusual local breeding circumstances may offer a unique opportunity to identify associated SAS and TVD genes in the DdB, as well as in other dog breeds. Copyright © 2013 Elsevier Ltd. All rights reserved.

Whole Exome Sequencing Identifies de Novo Mutations in GATA6 Associated with Congenital Diaphragmatic Hernia

PubMed Central

Yu, Lan; Bennett, James T.; Wynn, Julia; Carvill, Gemma L.; Cheung, Yee Him; Shen, Yufeng; Mychaliska, George B.; Azarow, Kenneth S.; Crombleholme, Timothy M.; Chung, Dai H.; Potoka, Douglas; Warner, Brad W.; Bucher, Brian; Lim, Foong-Yen; Pietsch, John; Stolar, Charles; Aspelund, Gudrun; Arkovitz, Marc S.; Mefford, Heather; Chung, Wendy K.

2014-01-01

Background Congenital diaphragmatic hernia (CDH) is a common birth defect affecting 1 in 3,000 births. It is characterized by herniation of abdominal viscera through an incompletely formed diaphragm. Although chromosomal anomalies and mutations in several genes have been implicated, the cause for most patients is unknown. Methods We used whole exome sequencing in two families with CDH and congenital heart disease, and identified mutations in GATA6 in both. Results In the first family, we identified a de novo missense mutation (c.1366C>T, p.R456C) in a sporadic CDH patient with tetralogy of Fallot. In the second, a nonsense mutation (c.712G>T, p.G238*) was identified in two siblings with CDH and a large ventricular septal defect. The G238* mutation was inherited from their mother, who was clinically affected with congenital absence of the pericardium, patent ductus arteriosus, and intestinal malrotation. Deep sequencing of blood and saliva derived DNA from the mother suggested somatic mosaicism as an explanation for her milder phenotype, with only approximately 15% mutant alleles. To determine the frequency of GATA6 mutations in CDH, we sequenced the gene in 378 patients with CDH. We identified one additional de novo mutation (c.1071delG, p.V358Cfs34*). Conclusions Mutations in GATA6 have been previously associated with pancreatic agenesis and congenital heart disease. We conclude that, in addition to the heart and the pancreas, GATA6 is involved in development of two additional organs, the diaphragm and the pericardium. In addition we have shown that de novo mutations can contribute to the development of CDH, a common birth defect. PMID:24385578

Inheritance patterns of enzymes and serum proteins of mallard-black duck hybrids

USGS Publications Warehouse

Morgan, R.P.; Meritt, D.W.; Block, S.B.; Cole, M.

1984-01-01

From 1974 to 1976, a breeding program was used to produce hybrids of black ducks and mallards for the evaluation of inheritance patterns of serum proteins and serum, liver and muscle enzymes. In addition to the crosses designed to produce hybrids, a series of matings in 1975 and 1976 were designed to evaluate inheritance patterns of a hybrid with either a black duck or mallard. At the F1 level, hybrids were easily distinguished using serum proteins. However, once a hybrid was crossed back to either a mallard or black duck, only 12-23% of the progeny were distinguishable from black ducks or mallards using serum proteins and 23-39% using esterases. Muscle, serum and liver enzymes were similar between the two species.

Inheritance patterns of enzymes and serum proteins of mallard-black duck hybrids

USGS Publications Warehouse

Morgan, R.P.; Meritt, D.W.; Block, S.B.; Cole, M.A.; Sulkin, S.T.; Lee, F.B.; Henny, C.J.

1984-01-01

From 1974 to 1976, a breeding program was used to produce hybrids of black ducks and mallards for the evaluation of inheritance patterns of serum proteins and serum, liver and muscle enzymes. In addition to the crosses designed to produce hybrids, a series of matings in 1975 and 1976 were designed to evaluate inheritance patterns of a hybrid with either a black duck or mallard. At the F1 level, hybrids were easily distinguished using serum proteins. However, once a hybrid was crossed back to either a mallard or black duck, only 12?23% of the progeny were distinguishable from black ducks or mallards using serum proteins and 23?39% using esterases. Muscle, serum and liver enzymes were similar between the two species.

Concepts of Kinship Relations and Inheritance in Childhood and Adolescence

ERIC Educational Resources Information Center

Williams, Joanne M.; Smith, Lesley A.

2010-01-01

This paper examines the development and consistency of children's (4, 7, 10, and 14 years) naive concepts of inheritance using three tasks. A modified adoption task asked participants to distinguish between biological and social parentage in their predictions and explanations of the origins of different feature types (physical characteristics,…

A dominantly inherited form of arthrogryposis multiplex congenita with unusual dermatoglyphics.

PubMed

Sack, G H

1978-12-01

A father and daughter with arthrogryposis multiplex congenita and similar dermatoglyphic patterns are described. No evidence was found of chromosomal abnormality, neuropathy or myopathy, and there were no other affected family members. The findings are compatible with autosomal dominant inheritance.

An exploration of attitudes towards pedigree dogs and their disorders as expressed by a sample of companion animal veterinarians in New Zealand.

PubMed

Farrow, T; Keown, A J; Farnworth, M J

2014-09-01

To explore veterinary perceptions of inherited disorders in pedigree dogs within New Zealand and how these affect animal health and welfare. An online questionnaire was distributed to the 647 members of the Companion Animal Society of the New Zealand Veterinary Association using an online survey system. The questionnaire collected details of practitioners, pedigree dog breeds and disorders most often encountered in practice, and responses to questions and statements regarding inherited disorders and pedigree dogs. Of the 216 respondents, 194 (89.8%) believed inherited disorders in dogs were a significant issue. The most commonly identified breeds presenting with inherited disorders were Boxer, Bulldog and German Shepherd dog. The most commonly reported inherited disorders were hip dysplasia, brachycephalic syndromes and elbow dysplasia. Of 207 respondents, 100 (48.3%) had advised clients against purchasing a pedigree dog due to common inherited disorders and 183 (85.6%) considered the health and welfare of some breeds to be too compromised to continue breeding. Of 199 respondents, 132 (66.3%) reported seeing no change in prevalence of inherited conditions, 103/204 (50.5%) reported seeing a positive change in attitudes towards inherited disorders among dog owners, and 81/207 (39.1%) thought legislative support would help decrease inherited disorders in pedigree dogs. Attitudes were not associated with time since graduation or ownership of a New Zealand Kennel Club registered breed of dog. The most common suggestions to decrease prevalence of inherited disorders were to alter breed standards, educate public or buyers and compulsory genetic testing. Among respondents, veterinarians considered inherited disorders as significant issues in a number of pedigree breeds. Veterinarians were concerned about inherited disorders in pedigree dogs, felt they had an obligation to treat such animals and were supportive of measures to make genetic testing for inheritable disorders a

More evidence for non-maternal inheritance of mitochondrial DNA?

PubMed

Bandelt, H-J; Kong, Q-P; Parson, W; Salas, A

2005-12-01

A single case of paternal co-transmission of mitochondrial DNA (mtDNA) in humans has been reported so far. To find potential instances of non-maternal inheritance of mtDNA. Published medical case studies (of single patients) were searched for irregular mtDNA patterns by comparing the given haplotype information for different clones or tissues with the worldwide mtDNA database as known to date-a method that has proved robust and reliable for the detection of flawed mtDNA sequence data. More than 20 studies were found reporting clear cut instances with mtDNAs of different ancestries in single individuals. As examples, cases are reviewed from recent published reports which, at face value, may be taken as evidence for paternal inheritance of mtDNA or recombination. Multiple types (or recombinant types) of quite dissimilar mitochondrial DNA from different parts of the known mtDNA phylogeny are often reported in single individuals. From re-analyses and corrigenda of forensic mtDNA data, it is apparent that the phenomenon of mixed or mosaic mtDNA can be ascribed solely to contamination and sample mix up.

Major effect of inherited rheology weakening in the crust and mantle on continental intraplate strain and seismicity rates

NASA Astrophysics Data System (ADS)

Gueydan, Frédéric; Mazzotti, Stephane

2017-04-01

Stable Continental Regions (SCR, i.e., intraplate) are commonly viewed as non-deforming and very high resistance lithosphere domains, except in localized regions of higher strain and seismicity rates that often related to fossilized tectonic zones acting as weaker domains (e.g., Rhine Graben, New Madrid). Two main categories of models have been proposed to explain strain concentration in SCR: Local stress concentration (fault intersection, erosion pulse, …) and local lithosphere weakness (high geotherm, mantle anisotropy, …). In order to test the respective role of these various parameters of the stress - rheology - strain relationship, we propose a simple 1D model to quantify first-order continental strain rate variations using laboratory and field-based rheology laws for the crust and mantle. In particular, we include new strain-weakening rheologies in order to simulate tectonic heritage. Within the framework of near-failure equilibrium between tectonic forces and strain rates, we show that inherited rheology weakening plays a fundamental role in allowing for and explaining strain and seismicity concentration in intraplate weak zones. A comparison with empirical strain rate estimations in SCR and intraplate weak zones shows that inherited weakening rheologies can increase local strain rates by as much as three orders of magnitude, about one to two orders higher than that permitted by other processes such as stress concentration, thermal anomaly, etc.

Extrachromosomal inheritance in Schizosaccharomyces pombe. I. Evidence for an extrakaryotically inherited mutation conferring resistance to antimycin.

PubMed

Wolf, K; Burger, G; Lang, B; Kaudewitz, F

1976-02-27

In crosses of [ANTr8] with auxotrophic strains, resistance to antimycin segregates almost 50:50 in random spore analysis with a slight preponderance for the sensitivity allele. Tetrad analysis, however, shows all possible types of tetrads (2:2; 3:1; 1:3; 4:0; 0:4 resistant versus sensitive) with an excess of 2:2 segregations and sectoring of colonies on antimycin medium indicating an extrachromosomal mode of inheritance. The overall ratio of resistant versus sensitive spores is the same as compared with random spore data. Using a mutant blocked in meiosis (mei 1) mitotic segregation of stable diploids is achieved, leading to a ratio of 20% resistant to 80% sensitive clones. Possible reasons for the bias in transmission of the resistance determinant is discussed.

Chloroplast SSR polymorphisms in the Compositae and the mode of organellar inheritance in Helianthus annuus.

PubMed

Wills, David M; Hester, Melissa L; Liu, Aizhong; Burke, John M

2005-03-01

Because organellar genomes are often uniparentally inherited, chloroplast (cp) and mitochondrial (mt) DNA polymorphisms have become the markers of choice for investigating evolutionary issues such as sex-biased dispersal and the directionality of introgression. To the extent that organellar inheritance is strictly maternal, it has also been suggested that the insertion of transgenes into either the chloroplast or mitochondrial genomes would reduce the likelihood of gene escape via pollen flow from crop fields into wild plant populations. In this paper we describe the adaptation of chloroplast simple sequence repeats (cpSSRs) for use in the Compositae. This work resulted in the identification of 12 loci that are variable across the family, seven of which were further shown to be highly polymorphic within sunflower (Helianthus annuus). We then used these markers, along with a novel mtDNA restriction fragment length polymorphism (RFLP), to investigate the mode of organellar inheritance in a series of experimental crosses designed to mimic the initial stages of crop-wild hybridization in sunflower. Although we cannot rule out the possibility of extremely rare paternal transmission, our results provide the best evidence to date of strict maternal organellar inheritance in sunflower, suggesting that organellar gene containment may be a viable strategy in sunflower. Moreover, the portability of these markers suggests that they will provide a ready source of cpDNA polymorphisms for use in evolutionary studies across the Compositae.

Ten-year study of postoperative complications following dental extractions in patients with inherited bleeding disorders.

PubMed

Hsieh, J-T; Klein, K; Batstone, M

2017-09-01

Dental extractions challenge the body's haemostatic mechanism. Postoperative bleeding from dental extraction can be prolonged, or even life threatening in patients with inherited bleeding disorders. Pre- and postoperative clotting factor replacements or systemic desmopressin (ddAVP) have been advocated at our institution to prevent bleeding complications in these patients. This study aimed to assess the postoperative bleeding rate in patients with inherited bleeding disorders that underwent dental extractions at our institution between 2003 and 2012. Patients with inherited bleeding disorders such as haemophilia A, haemophilia B, and von Willebrand's disease were included. Retrospective chart review was conducted. The result showed 53 extraction events occurred in 45 patients over the 10-year period. Ten out of 53 extraction events (18.9%) had postoperative bleeding requiring further factor replacement or ddAVP. Postoperative bleeding in one patient with mild haemophilia A was complicated by the development of inhibitors. Type and severity of bleeding disorder, bone removal, and use of a local haemostatic agent did not have any significant effect on postoperative bleeding. Despite the use of perioperative factors and desmopressin, the postoperative bleeding rates remain high for patients with inherited bleeding disorders. More studies are required to assess the safety and effectiveness of using local haemostatic control to achieve haemostasis following extractions. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Inherit Space

NASA Technical Reports Server (NTRS)

Giarratano, Joseph C.; Jenks, K. C.

1997-01-01

The objective of the proposed research was to begin development of a unique educational tool targeted at educating and inspiring young people 12-16 years old about NASA and the Space Program. Since these young people are the future engineers, scientists and space pioneers, the nurturing of their enthusiasm and interest is of critical importance to the Nation. This summer the basic infrastructure of the tool was developed in the context of an educational game paradigm. The game paradigm has achieved remarkable success in maintaining the interest of young people in a self-paced, student-directed learning environment. This type of environment encourages student exploration and curiosity which are exactly the traits that future space pioneers need to develop to prepare for the unexpected. The Inherit Space Educational Tool is an open-ended learning environment consisting of a finite-state machine classic adventure game paradigm. As the young person explores this world, different obstacles must be overcome. Rewards will be offered such as using the flight simulator to fly around and explore Titan. This simulator was modeled on conventional Earth flight simulators but has been considerably enhanced to add texture mapping of Titan's atmosphere utilizing the latest information from the NASA Galileo Space Probe. Additional scenery was added to provide color VGA graphics of a futuristic research station on Titan as well as an interesting story to keep the youngster's attention. This summer the game infrastructure has been developed as well as the Titan Flight Simulator. A number of other enhancements are planned.

The Puzzle of Inheritance: Genetics and the Methods of Science.

ERIC Educational Resources Information Center

Cutter, Mary Ann G.; Drexler, Edward; Friedman, B. Ellen; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Rossiter, Belinda; Zola, John

This instructional module contains a description of the Human Genome Project (HGP). A discussion of issues in the philosophy of science and some of the ethical, legal, and social implications of research in genetics, and a survey of fundamental genetics concepts and of new, nontraditional concepts of inheritance are also included. Six…

Frameshift-mutation-derived peptides as tumor-specific antigens in inherited and spontaneous colorectal cancer.

PubMed

Saeterdal, I; Bjørheim, J; Lislerud, K; Gjertsen, M K; Bukholm, I K; Olsen, O C; Nesland, J M; Eriksen, J A; Møller, M; Lindblom, A; Gaudernack, G

2001-11-06

The functional role and specificity of tumor infiltrating lymphocytes (TIL) is generally not well characterized. Prominent lymphocyte infiltration is the hallmark of the most common form of hereditary colon cancer, hereditary nonpolyposis colon cancer (HNPCC) and the corresponding spontaneous colon cancers with the microsatellite instability (MSI) phenotype. These cancers are caused by inherited or acquired defects in the DNA mismatch-repair machinery. The molecular mechanism behind the MSI phenotype provides a clue to understanding the lymphocyte reaction by allowing reliable prediction of potential T cell epitopes created by frameshift mutations in candidate genes carrying nucleotide repeat sequences, such as TGF beta RII and BAX. These tumors therefore represent an interesting human system for studying TIL and characterizing tumor-specific T cells. We here describe T cell reactivity against several T helper cell epitopes, representing a common frameshift mutation in TGF beta RII, in TIL and peripheral blood lymphocytes from patients with MSI(+) tumors. The peptide SLVRLSSCVPVALMSAMTTSSSQ was recognized by T cells from two of three patients with spontaneous MSI(+) colon cancers and from all three patients with HNPCC. Because such mutations are present in 90% of cancers within this patient group, these newly characterized epitopes provide attractive targets for cancer vaccines, including a prophylactic vaccine for individuals carrying a genetic disposition for developing HNPCC.

Frameshift-mutation-derived peptides as tumor-specific antigens in inherited and spontaneous colorectal cancer

PubMed Central

Sæterdal, Ingvil; Bjørheim, Jens; Lislerud, Kari; Gjertsen, Marianne K.; Bukholm, Ida K.; Olsen, Ole Christian; Nesland, Jahn M.; Eriksen, Jon Amund; Møller, Mona; Lindblom, Annika; Gaudernack, Gustav

2001-01-01

The functional role and specificity of tumor infiltrating lymphocytes (TIL) is generally not well characterized. Prominent lymphocyte infiltration is the hallmark of the most common form of hereditary colon cancer, hereditary nonpolyposis colon cancer (HNPCC) and the corresponding spontaneous colon cancers with the microsatellite instability (MSI) phenotype. These cancers are caused by inherited or acquired defects in the DNA mismatch–repair machinery. The molecular mechanism behind the MSI phenotype provides a clue to understanding the lymphocyte reaction by allowing reliable prediction of potential T cell epitopes created by frameshift mutations in candidate genes carrying nucleotide repeat sequences, such as TGFβRII and BAX. These tumors therefore represent an interesting human system for studying TIL and characterizing tumor-specific T cells. We here describe T cell reactivity against several T helper cell epitopes, representing a common frameshift mutation in TGFβRII, in TIL and peripheral blood lymphocytes from patients with MSI+ tumors. The peptide SLVRLSSCVPVALMSAMTTSSSQ was recognized by T cells from two of three patients with spontaneous MSI+ colon cancers and from all three patients with HNPCC. Because such mutations are present in 90% of cancers within this patient group, these newly characterized epitopes provide attractive targets for cancer vaccines, including a prophylactic vaccine for individuals carrying a genetic disposition for developing HNPCC. PMID:11687624

A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases.

PubMed

Bullich, Gemma; Domingo-Gallego, Andrea; Vargas, Iván; Ruiz, Patricia; Lorente-Grandoso, Laura; Furlano, Mónica; Fraga, Gloria; Madrid, Álvaro; Ariceta, Gema; Borregán, Mar; Piñero-Fernández, Juan Alberto; Rodríguez-Peña, Lidia; Ballesta-Martínez, Maria Juliana; Llano-Rivas, Isabel; Meñica, Mireia Aguirre; Ballarín, José; Torrents, David; Torra, Roser; Ars, Elisabet

2018-05-22

Molecular diagnosis of inherited kidney diseases remains a challenge due to their expanding phenotypic spectra as well as the constantly growing list of disease-causing genes. Here we develop a comprehensive approach for genetic diagnosis of inherited cystic and glomerular nephropathies. Targeted next generation sequencing of 140 genes causative of or associated with cystic or glomerular nephropathies was performed in 421 patients, a validation cohort of 116 patients with previously known mutations, and a diagnostic cohort of 207 patients with suspected inherited cystic disease and 98 patients with glomerular disease. In the validation cohort, a sensitivity of 99% was achieved. In the diagnostic cohort, causative mutations were found in 78% of patients with cystic disease and 62% of patients with glomerular disease, mostly familial cases, including copy number variants. Results depict the distribution of different cystic and glomerular inherited diseases showing the most likely diagnosis according to perinatal, pediatric and adult disease onset. Of all the genetically diagnosed patients, 15% were referred with an unspecified clinical diagnosis and in 2% genetic testing changed the clinical diagnosis. Therefore, in 17% of cases our genetic analysis was crucial to establish the correct diagnosis. Complex inheritance patterns in autosomal dominant polycystic kidney disease and Alport syndrome were suspected in seven and six patients, respectively. Thus, our kidney-disease gene panel is a comprehensive, noninvasive, and cost-effective tool for genetic diagnosis of cystic and glomerular inherited kidney diseases. This allows etiologic diagnosis in three-quarters of patients and is especially valuable in patients with unspecific or atypical phenotypes. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

PubMed Central

Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; Azbaoui, Safaa El; Agader, Aomar; Hassani, Amal; Hafidi, Naima El; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

2015-01-01

Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

Family Communication in Inherited Cardiovascular Conditions in Ireland.

PubMed

Whyte, Sinead; Green, Andrew; McAllister, Marion; Shipman, Hannah

2016-12-01

Over 100,000 individuals living in Ireland carry a mutated gene for an inherited cardiac condition (ICC), most of which demonstrate an autosomal dominant pattern of inheritance. First-degree relatives of individuals with these mutations are at a 50 % risk of being a carrier: disclosing genetic information to family members can be complex. This study explored how families living in Ireland communicate genetic information about ICCs and looked at the challenges of communicating information, factors that may affect communication and what influence this had on family relationships. Face to face interviews were conducted with nine participants using an approved topic guide and results analysed using thematic analysis. The participants disclosed that responsibility to future generations, gender, proximity and lack of contact all played a role in family communication. The media was cited as a source of information about genetic information and knowledge of genetic information tended to have a positive effect on families. Results from this study indicate that individuals are willing to inform family members, particularly when there are children and grandchildren at risk, and different strategies are utilised. Furthermore, understanding of genetics is partially regulated not only by their families, but by the way society handles information. Therefore, genetic health professionals should take into account the familial influence on individuals and their decision to attend genetic services, and also that of the media.

Multi-omics Evidence for Inheritance of Energy Pathways in Red Blood Cells.

PubMed

Weisenhorn, Erin M M; van T Erve, Thomas J; Riley, Nicholas M; Hess, John R; Raife, Thomas J; Coon, Joshua J

2016-12-01

Each year over 90 million units of blood are transfused worldwide. Our dependence on this blood supply mandates optimized blood management and storage. During storage, red blood cells undergo degenerative processes resulting in altered metabolic characteristics which may make blood less viable for transfusion. However, not all stored blood spoils at the same rate, a difference that has been attributed to variable rates of energy usage and metabolism in red blood cells. Specific metabolite abundances are heritable traits; however, the link between heritability of energy metabolism and red blood cell storage profiles is unclear. Herein we performed a comprehensive metabolomics and proteomics study of red blood cells from 18 mono- and di-zygotic twin pairs to measure heritability and identify correlations with ATP and other molecular indices of energy metabolism. Without using affinity-based hemoglobin depletion, our work afforded the deepest multi-omic characterization of red blood cell membranes to date (1280 membrane proteins and 330 metabolites), with 119 membrane protein and 148 metabolite concentrations found to be over 30% heritable. We demonstrate a high degree of heritability in the concentration of energy metabolism metabolites, especially glycolytic metabolites. In addition to being heritable, proteins and metabolites involved in glycolysis and redox metabolism are highly correlated, suggesting that crucial energy metabolism pathways are inherited en bloc at distinct levels. We conclude that individuals can inherit a phenotype composed of higher or lower concentrations of these proteins together. This can result in vastly different red blood cells storage profiles which may need to be considered to develop precise and individualized storage options. Beyond guiding proper blood storage, this intimate link in heritability between energy and redox metabolism pathways may someday prove useful in determining the predisposition of an individual toward metabolic

Systems genomics analysis centered on epigenetic inheritance supports development of a unified theory of biology.

PubMed

Sharma, Abhay

2015-11-01

New discoveries are increasingly demanding integration of epigenetics, molecular biology, genomic networks and physiology with evolution. This article provides a proof of concept for evolutionary transgenerational systems biology, proposed recently in the context of epigenetic inheritance in mammals. Gene set enrichment analysis of available genome-level mammalian data presented here seem consistent with the concept that: (1) heritable information about environmental effects in somatic cells is communicated to the germline by circulating microRNAs (miRNAs) or other RNAs released in physiological fluids; (2) epigenetic factors including miRNA-like small RNAs, DNA methylation and histone modifications are propagated across generations via gene networks; and (3) inherited epigenetic variations in the form of methylated cytosines are fixed in the population as thymines over the evolutionary time course. The analysis supports integration of physiology and epigenetics with inheritance and evolution. This may catalyze efforts to develop a unified theory of biology. © 2015. Published by The Company of Biologists Ltd.

Deep Dermatophytosis and Inherited CARD9 Deficiency

PubMed Central

Vincent, Quentin B.; Liu, Luyan; Cypowyj, Sophie; Prando, Carolina; Migaud, Mélanie; Taibi, Lynda; Ammar-Khodja, Aomar; Stambouli, Omar Boudghene; Guellil, Boumediene; Jacobs, Frederique; Goffard, Jean-Christophe; Schepers, Kinda; del Marmol, Véronique; Boussofara, Lobna; Denguezli, Mohamed; Larif, Molka; Bachelez, Hervé; Michel, Laurence; Lefranc, Gérard; Hay, Rod; Jouvion, Gregory; Chretien, Fabrice; Fraitag, Sylvie; Bougnoux, Marie-Elisabeth; Boudia, Merad

2014-01-01

BACKGROUND Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. METHODS We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain–containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. RESULTS Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. CONCLUSIONS All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.) PMID:24131138

Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken

PubMed Central

Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

2018-01-01

Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers. PMID:29642504

Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken.

PubMed

Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

2018-04-08

Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism ( ACACA , FASN , SCD , ACSL5 , FADS2 , FABP1 , APOA4 and ME1 ). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers.

Inversion of inherited thrusts by wastewater injection induced seismicity at the Val d’Agri oilfield (Italy)

NASA Astrophysics Data System (ADS)

Buttinelli, M.; Improta, L.; Bagh, S.; Chiarabba, C.

2016-11-01

Since 2006 wastewater has been injected below the Val d’Agri Quaternary basin, the largest on-land oilfield in Europe, inducing micro-seismicity in the proximity of a high-rate injection well. In this study, we have the rare opportunity to revise a massive set of 2D/3D seismic and deep borehole data in order to investigate the relationship between the active faults that bound the basin and the induced earthquakes. Below the injection site we identify a Pliocene thrusts and back-thrusts system inherited by the Apennines compression, with no relation with faults bounding the basin. The induced seismicity is mostly confined within the injection reservoir, and aligns coherently with a NE-dipping back-thrust favorably oriented within the current extensional stress field. Earthquakes spread upwards from the back-thrust deep portion activating a 2.5-km wide patch. Focal mechanisms show a predominant extensional kinematic testifying to an on-going inversion of the back-thrust, while a minor strike-slip compound suggests a control exerted by a high angle inherited transverse fault developed within the compressional system, possibly at the intersection between the two fault sets. We stress that where wastewater injection is active, understanding the complex interaction between injection-linked seismicity and pre-existing faults is a strong requisite for safe oilfield exploitation.

The MGS Avionics System Architecture: Exploring the Limits of Inheritance