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1

Three different ABCA4 mutations in the same large family with several consanguineous loops affected with autosomal recessive cone–rod dystrophy  

Microsoft Academic Search

A large multiplex family presumably affected with autosomal recessive cone–rod dystrophy (CRD) was ascertained from Israel. In this family of Christian Arab ancestry with six consanguineous loops, linkage analysis failed to identify homozygosity in all six nuclear families at any of the three arCORD loci hitherto reported. However, homozygosity was found at the CORD3 locus for two nuclear families and

Dominique Ducroq; Stavit Shalev; Aviv Habib; Arnold Munnich; Josseline Kaplan; Jean-Michel Rozet; J-M Rozet

2006-01-01

2

Maternally inherited mitochondrial DNA disease in consanguineous families  

PubMed Central

Mitochondrial respiratory chain disease represents one of the most common inborn errors of metabolism and is genetically heterogeneous, with biochemical defects arising from mutations in the mitochondrial genome (mtDNA) or the nuclear genome. As such, inheritance of mitochondrial respiratory chain disease can either follow dominant or recessive autosomal (Mendelian) inheritance patterns, the strictly matrilineal inheritance observed with mtDNA point mutations or X-linked inheritance. Parental consanguinity in respiratory chain disease is often assumed to infer an autosomal recessive inheritance pattern, and the analysis of mtDNA may be overlooked in the pursuit of a presumed nuclear genetic defect. We report the histochemical, biochemical and molecular genetic investigations of two patients with suspected mitochondrial disease who, despite being born to consanguineous first-cousin parents, were found to harbour well-characterised pathogenic mtDNA mutations, both of which were maternally transmitted. Our findings highlight that any diagnostic algorithm for the investigation of mitochondrial respiratory chain disease must include a full and complete analysis of the entire coding sequence of the mitochondrial genome in a clinically relevant tissue. An autosomal basis for respiratory chain disease should not be assumed in consanguineous families and that ‘maternally inherited consanguineous' mitochondrial disease may thus be going undiagnosed.

Alston, Charlotte L; He, Langping; Morris, Andrew A; Hughes, Imelda; Goede, Christian de; Turnbull, Douglass M; McFarland, Robert; Taylor, Robert W

2011-01-01

3

Moroccan consanguineous family with Becker myotonia and review  

PubMed Central

Myotonia congenita is a genetic muscle disorder characterized by clinical and electrical myotonia, muscle hypertrophy, and stiffness. It is inherited as either autosomal-dominant or –recessive, known as Thomsen and Becker diseases, respectively. These diseases are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe muscle stiffness and pain. Mutations in the muscular voltage-dependent chloride channel gene (CLCN1), located at 7q35, have been found in both types. We report here the case of a Moroccan consanguineous family with a myotonic autosomal-recessive condition in two children. The molecular studies showed that the patients reported here are homozygous for mutation p.Gly482Arg in the CLCN1 gene. The parents were heterozygote carriers for mutation p.Gly482Arg. This diagnosis allowed us to provide an appropriate management to the patients and to make a genetic counselling to their family.

Ratbi, Ilham; Elalaoui, Siham Chafai; Escudero, Adela; Kriouile, Yamina; Molano, Jesus; Sefiani, Abdelaziz

2011-01-01

4

Moroccan consanguineous family with Becker myotonia and review.  

PubMed

Myotonia congenita is a genetic muscle disorder characterized by clinical and electrical myotonia, muscle hypertrophy, and stiffness. It is inherited as either autosomal-dominant or -recessive, known as Thomsen and Becker diseases, respectively. These diseases are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe muscle stiffness and pain. Mutations in the muscular voltage-dependent chloride channel gene (CLCN1), located at 7q35, have been found in both types. We report here the case of a Moroccan consanguineous family with a myotonic autosomal-recessive condition in two children. The molecular studies showed that the patients reported here are homozygous for mutation p.Gly482Arg in the CLCN1 gene. The parents were heterozygote carriers for mutation p.Gly482Arg. This diagnosis allowed us to provide an appropriate management to the patients and to make a genetic counselling to their family. PMID:22346025

Ratbi, Ilham; Elalaoui, Siham Chafai; Escudero, Adela; Kriouile, Yamina; Molano, Jesus; Sefiani, Abdelaziz

2011-10-01

5

Five new consanguineous families with horizontal gaze palsy and progressive scoliosis and novel ROBO3 mutations  

Microsoft Academic Search

Horizontal gaze palsy and progressive scoliosis (HGPPS) is an autosomal recessive neurologic disorder caused by homozygous or compound heterozygous mutations in the ROBO3 gene on chromosome 11. We clinically evaluated seven individuals with HGPPS from five previously unreported consanguineous families. We sequenced ROBO3 in all affected individuals, additional unaffected members of each family, and ethnic controls. All affected individuals had

Khaled K. Abu-Amero; Hesham al Dhalaan; Zayed al Zayed; Ali Hellani; Thomas M. Bosley

2009-01-01

6

Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness  

Microsoft Academic Search

Nonsyndromic autosomal recessive deafness accounts for 80% of hereditary deafness. To date, 52 loci responsible for autosomal recessive deafness have been mapped and 24 genes identified. Here, we report a large inbred Brazilian pedigree with 26 subjects affected by prelingual deafness. Given the extensive consanguinity found in this pedigree, the most probable pattern of inheritance is autosomal recessive. However, our

Karina Lezirovitz; Eliete Pardono; Maria T B de Mello Auricchio; Fernando L de Carvalho e Silva; Juliana J Lopes; Ronaldo S Abreu-Silva; Jihane Romanos; Ana C Batissoco; Regina C Mingroni-Netto

2008-01-01

7

Increased availability of family donors for hematopoietic stem cell transplantation in a population with increased incidence of consanguinity.  

PubMed

The study was planned to determine the frequency of parental and non-sibling family donor transplants in our center and to investigate the rate of familial donor availability at two HLA-typing laboratories in Turkey. Among 203 patients who underwent hematopoietic stem cell transplantation (HSCT), 151 (74.4%) received stem cells from siblings, 48 (23.6%) from non-sibling family donors, two (1.0%) from unrelated cord blood, and two (1.0%) autologous transplantation. Of these 48 patients received stem cells from non-sibling family donors; donors were mothers for 26 (12.8%), fathers for 20 (9.9%), and aunts for two (1.0%). The rate of transplants from parental donors was 22.6% in this patient population with increased frequency of inherited diseases (58.1%). Among these 203 patients, there was consanguinity between parents in 60.6% of the patients. Of 833 subjects applying as donor candidates to HLA-typing laboratories, 527 (63.3%) had HLA 6/6 identical family donors. Among 527 full-matched donors, 479 (90.9%) were sibling, 21 (4.0%) were fathers, and 17 (3.2%) were mothers. The remaining 10 (1.9%) were other relatives. The results have shown that the unfavorable factor of consanguinity marriage may increase the availability of family donors for HSCT in particularly developing countries where large donor registries are lacking. PMID:20636407

Balc?, Yasemin I; Tavil, Betul; Tan, Cagman S; Ozgur, Tuba T; Bulum, Burcu; Cetin, Mualla; Balc?, Mustafa; Yalc?n, Songul; Tezcan, Ilhan; Uckan, Duygu

2010-07-14

8

Association of Pathogenic Mutations in TULP1 With Retinitis Pigmentosa in Consanguineous Pakistani Families  

PubMed Central

Objective To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa in 5 consanguineous Pakistani families. Methods Affected individuals in the families underwent a detailed ophthalmological examination that consisted of fundus photography and electroretinography. Blood samples were collected from all participating family members, and genomic DNA was extracted. A genome-wide linkage scan was performed, followed by exclusion analyses among our cohort of nuclear consanguineous families with microsatellite markers spanning the TULP1 locus on chromosome 6p. Two-point logarithm of odds scores were calculated, and all coding exons of TULP1 were sequenced bidirectionally. Results The results of ophthalmological examinations among affected individuals in these 5 families were suggestive of retinitis pigmentosa. The genome-wide linkage scan localized the disease interval to chromosome 6p, harboring TULP1 in 1 of 5 families, and sequential analyses identified a single base pair substitution in TULP1 that results in threonine to alanine substitution (p.T380A). Subsequently, we investigated our entire cohort of families with autosomal recessive retinitis pigmentosa and identified 4 additional families with linkage to chromosome 6p, all of them harboring a single base pair substitution in TULP1 that results in lysine to arginine substitution (p.K489R). Results of single-nucleotide polymorphism haplotype analyses were suggestive of a common founder in these 4 families. Conclusion Pathogenic mutations in TULP1 are responsible for the autosomal recessive retinitis pigmentosa phenotype in these consanguineous Pakistani families, with a single ancestral mutation in TULP1 causing the disease phenotype in 4 of 5 families. Clinical Relevance Clinical and molecular characterization of pathogenic mutations in TULP1 will increase our understanding of retinitis pigmentosa at a molecular level.

Iqbal, Muhammad; Naeem, Muhammad Asif; Riazuddin, S. Amer; Ali, Shahbaz; Farooq, Tahir; Qazi, Zaheeruddin A.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Saima; Sieving, Paul A.; Hejtmancik, J. Fielding; Riazuddin, Sheikh

2012-01-01

9

Developing and evaluating a culturally appropriate genetic service for consanguineous South Asian families.  

PubMed

Blackburn with Darwen Primary Care Trust (PCT) provides services to a substantial Asian population in which the practice of consanguineous marriage is common and there is a high incidence of autosomal recessive disorders. The aim was to provide and evaluate a genetic service accessible to consanguineous families from the South Asian community who had a child affected by an autosomal recessive disorder. Information on genetic risk was provided along with the offer of genetic testing for members of the extended family to identify gene carriers and facilitate informed reproductive choices. An Urdu-speaking health visitor was employed to establish a community-based, hospital-linked genetic service in conjunction with local paediatric and regional genetic services offered to parents who had an affected child and 71 of their relatives. The service was evaluated using a specifically designed questionnaire. There was a high uptake of the service (95% of index parents and 92% of relatives to whom it was offered) and a high uptake of carrier testing (94% of relatives to whom it was offered). Eight requests for prenatal diagnosis were made during the course of the service development. Many individuals stated they would consider genetic risk when making future marriage and reproductive plans. Input from a health care worker from the same ethnic background who provided information in their own language was highly valued. Family orientated genetic services for ethnic groups practicing consanguinity can be acceptable and effective when provided in a culturally appropriate manner. PMID:22460207

Khan, Nasaim; Benson, John; Macleod, Rhona; Kingston, Helen

2010-08-20

10

Clinical evaluation of two consanguineous families with homozygous mutations in BEST1  

PubMed Central

Purpose To describe the clinical and genetic findings in two consanguineous families with Best vitelliform macular dystrophy (BVMD) and homozygous mutations in the bestrophin-1 (BEST1) gene. Methods Ophthalmologic examination was performed in eight members of two families originating from Spain and Denmark. Mutation screening was performed using the Vitelliform Macular Dystrophy mutation array from Asper Biotech, and by the directed genomic sequencing of BEST1. Results Two homozygous mutations were detected in these families. Mutation c.936C>A (p.Asp312Glu) has been reported previously in a Danish family; here, we describe four additional individuals in this family demonstrating findings compatible with a severe dominant BVMD, albeit with reduced penetrance in heterozygotes. In the Spanish family, a novel homozygous missense mutation in exon 4, c.388 C>A (p.Arg130Ser), was identified in the siblings. Homozygous siblings demonstrated evidence of multifocal vitelliform retinopathy, whereas heterozygous family members presented findings ranging from isolated reduction of the electrooculogram Arden ratio to normal values on all clinical parameters. Conclusions As demonstrated in these consanguineous families, a great clinical variability is associated with homozygous mutations in BEST1, ranging from severe dominant BVMD with reduced penetrance in heterozygotes to autosomal recessive bestrophinopathy.

Pineiro-Gallego, Teresa; Alvarez, Maria; Pereiro, Ines; Campos, Severiano; Sharon, Dror; Schatz, Patrik

2011-01-01

11

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family  

PubMed Central

Background Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

2012-01-01

12

Clinical assessment and genomic landscape of a consanguineous family with three Kallmann syndrome descendants  

PubMed Central

Although some genes that cause Kallmann syndrome (KS) have been identified by traditional linkage analysis and candidate gene techniques, the syndrome's molecular etiology in the majority of patients remains poorly understood. In this paper, we present the clinical assessments of a consanguineous Han Chinese family with three KS descendants. To understand the molecular etiology of KS from a genome-wide perspective, we investigated the genome-wide profile of structural variation in this family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. The results revealed that the three affected individuals had common copy number variants (microdeletions) on chromosomes 1p21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL1, which causes X-linked KS. Two PCR assays were performed on these regions to validate the results obtained using the chips. In addition, genomic microdeletions in this region were verified in one of 29 Han Chinese sporadic KS cases and one of four other family cases, but not in 26 Han Chinese sporadic normosmic idiopathic hypogonadotropic hypogonadism cases and 100 unrelated Han Chinese normal controls. Our results provide a novel insight into the relative contributions of certain copy number variants to KS's molecular etiology and generate a list of interesting candidate regions for further studies.

Zhang, Shi-Lin; Tang, Yan-Ping; Wang, Tao; Yang, Jun; Rao, Ke; Zhao, Ling-Yun; Zhu, Wen-Zhen; Meng, Xiang-Hu; Wang, Shao-Gang; Liu, Ji-Hong; Yang, Wei-Min; Ye, Zhang-Qun

2011-01-01

13

Five new consanguineous families with horizontal gaze palsy and progressive scoliosis and novel ROBO3 mutations.  

PubMed

Horizontal gaze palsy and progressive scoliosis (HGPPS) is an autosomal recessive neurologic disorder caused by homozygous or compound heterozygous mutations in the ROBO3 gene on chromosome 11. We clinically evaluated seven individuals with HGPPS from five previously unreported consanguineous families. We sequenced ROBO3 in all affected individuals, additional unaffected members of each family, and ethnic controls. All affected individuals had severe horizontal gaze restriction, progressive scoliosis, and lower brainstem hypoplasia on neuroimaging, the hallmarks of this syndrome. One individual experienced head trauma with a right subdural hematoma associated with a right hemiparesis, observations that confirm clinically for the first time that corticospinal tracts in HGPPS are uncrossed. We found five novel homozygous ROBO3 mutations (four missense mutations and one base deletion) distributed throughout the extracellular domain of the gene. The ROBO3 gene does not appear to have an obvious hot spot area for mutations; therefore, we recommend sequencing all exons and exon-intron boundaries in patients with clinical and/or radiologic features of HGPPS. PMID:18829051

Abu-Amero, Khaled K; al Dhalaan, Hesham; al Zayed, Zayed; Hellani, Ali; Bosley, Thomas M

2008-10-01

14

Mutations in the ?-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa  

PubMed Central

Purpose This study was designed to identify pathogenic mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families. Methods Two consanguineous families affected with autosomal recessive RP were identified from the Punjab Province of Pakistan. All affected individuals underwent a thorough ophthalmologic examination. Blood samples were collected, and genomic DNAs were extracted. Exclusion analysis was completed, and two-point LOD scores were calculated. Bidirectional sequencing of the ? subunit of phosphodiesterase 6 (PDE6?) was completed. Results During exclusion analyses both families localized to chromosome 4p, harboring PDE6?, a gene previously associated with autosomal recessive RP. Sequencing of PDE6? identified missense mutations: c.1655G>A (p.R552Q) and c.1160C>T (p.P387L) in families PKRP161 and PKRP183, respectively. Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6? protein. Conclusions These results strongly suggest that mutations in PDE6? are responsible for the disease phenotype in the consanguineous Pakistani families.

Ali, Shahbaz; Riazuddin, S. Amer; Shahzadi, Amber; Nasir, Idrees A.; Khan, Shaheen N.; Husnain, Tayyab; Akram, Javed; Sieving, Paul A.; Hejtmancik, J. Fielding

2011-01-01

15

A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family.  

PubMed Central

Purpose To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition. Methods A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog–drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping was performed in DNA samples from available family members using a 700K single nucleotide polymorphism (SNP) microarray. Candidate genes present in the significantly large homozygous regions were screened for mutations using Sanger sequencing. Results The largest homozygous region (~11 Mb) in the affected family members was mapped to chromosome 9, which harbors deafness, autosomal recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation analysis of DFNB31 in the index patient identified a novel one-base-pair deletion (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13) and co-segregated with the disease in the family. Ophthalmic examination of the index patient and the affected siblings showed severe rod-cone dystrophy. Pure tone audiometry revealed a moderate hearing loss in the index patient, whereas the affected siblings were reported with more profound and early onset hearing impairment. Conclusions We report a novel truncating mutation in DFNB31 associated with severe rod-cone dystrophy and varying degrees of hearing impairment in a consanguineous family of Portuguese origin. This is the second report of DFNB31 implication in Usher type 2.

Bujakowska, Kinga; Mohand-Said, Saddek; Tronche, Sophie; Lancelot, Marie-Elise; Antonio, Aline; Germain, Aurore; Lonjou, Christine; Carpentier, Wassila; Sahel, Jose-Alain; Bhattacharya, Shomi; Zeitz, Christina

2011-01-01

16

Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness.  

PubMed

Recently the TMPRSS3 gene, which encodes a transmembrane serine protease, was found to be responsible for two non-syndromic recessive deafness loci located on human chromosome 21q22.3, DFNB8 and DFNB10. We found evidence for linkage to the DFNB8/10 locus in two unrelated consanguineous Tunisian families segregating congenital autosomal recessive sensorineural deafness. The audiometric tests showed a loss of hearing greater than 70 dB, in all affected individuals of both families. Mutation screening of TMPRSS3 revealed two novel missense mutations, W251C and P404L, altering highly conserved amino acids of the serine protease domain. Both mutations were not found in 200 control Tunisian chromosomes. The detection of naturally-occurring TMPRSS3 missense mutations in deafness families identifies functionally important amino acids. Comparative protein modeling of the TMPRSS3 protease domain predicted that W251C might lead to a structural rearrangement affecting the active site H257 and that P404L might alter the geometry of the active site loop and therefore affect the serine protease activity. PMID:11462234

Masmoudi, S; Antonarakis, S E; Schwede, T; Ghorbel, A M; Gratri, M; Pappasavas, M P; Drira, M; Elgaied-Boulila, A; Wattenhofer, M; Rossier, C; Scott, H S; Ayadi, H; Guipponi, M

2001-08-01

17

A distinctive autosomal recessive syndrome of severe disproportionate short stature with short long bones, brachydactyly, and hypotrichosis in two consanguineous Arab families.  

PubMed

Disproportionate short stature is a heterogeneous group of hereditary disorders, which are classified according to their mode of inheritance, their clinical skeletal and non-skeletal manifestations, and their radiological characteristics. Herein, we inform on eight individuals with severe disproportionate short stature from two unrelated consanguineous families of Arab-Muslim ancestry. The adult height of the affected individuals is between 112 cm and 127 cm, and is due to pre- and post-natal growth retardation, which probably manifests as early as the second trimester of pregnancy. At a young age, the phenotype is characterized by a short stature, a relatively large head, and a long triangular face, and this phenotype later evolves to one with in which the head is relatively small, the mandible is large and pointy. The affected individuals have normal cognitive abilities and lack any neurological deficits. Other typical features include a prominent nose, a voice with an unusual high-pitched sound, relatively small ears, clinodactyly, brachydactyly, small hands, hypoplastic fingernails, a waddling gait, and sparse hair post-pubertally. Typical skeletal changes include short long bones, especially the femurs and humeri, with mild metaphyseal changes and very short femoral necks. After due consideration of the other hereditary causes of disproportionate short stature and close examination of the pedigrees of the two families, we concluded that these eight individuals have the same hitherto unreported form of severe disproportionate short stature that is inherited in the autosomal recessive mode. PMID:22440536

Shalev, Stavit A; Spiegel, Ronen; Borochowitz, Zvi U

2012-03-03

18

Combining gene mapping and phenotype assessment for fast mutation finding in non-consanguineous autosomal recessive retinitis pigmentosa families  

PubMed Central

Among inherited retinal dystrophies, autosomal recessive retinitis pigmentosa (arRP) is the most genetically heterogenous condition with 32 genes currently known that account for ?60 % of patients. Molecular diagnosis thus requires the tedious systematic sequencing of 506 exons. To rapidly identify the causative mutations, we devised a strategy that combines gene mapping and phenotype assessment in small non-consanguineous families. Two unrelated sibships with arRP had whole-genome scan using SNP microchips. Chromosomal regions were selected by calculating a score based on SNP coverage and genotype identity of affected patients. Candidate genes from the regions with the highest scores were then selected based on phenotype concordance of affected patients with previously described phenotype for each candidate gene. For families RP127 and RP1459, 33 and 40 chromosomal regions showed possible linkage, respectively. By comparing the scores with the phenotypes, we ended with one best candidate gene for each family, namely tubby-like protein 1 (TULP1) and C2ORF71 for RP127 and RP1459, respectively. We found that RP127 patients were compound heterozygous for two novel TULP1 mutations, p.Arg311Gln and p.Arg342Gln, and that RP1459 patients were compound heterozygous for two novel C2ORF71 mutations, p.Leu777PhefsX34 and p.Leu777AsnfsX28. Phenotype assessment showed that TULP1 patients had severe early onset arRP and that C2ORF71 patients had a cone rod dystrophy type of arRP. Only two affected individuals in each sibship were sufficient to lead to mutation identification by screening the best candidate gene selected by a combination of gene mapping and phenotype characterization.

Hebrard, Maxime; Manes, Gael; Bocquet, Beatrice; Meunier, Isabelle; Coustes-Chazalette, Delphine; Herald, Emilie; Senechal, Audrey; Bolland-Auge, Anne; Zelenika, Diana; Hamel, Christian P

2011-01-01

19

Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure  

PubMed Central

Background The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10–15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients. Methodology/Principal Findings We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LODmax of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations. Conclusions/Significance We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function.

Caburet, Sandrine; Zavadakova, Petra; Ben-Neriah, Ziva; Bouhali, Kamal; Dipietromaria, Aurelie; Charon, Celine; Besse, Celine; Laissue, Paul; Chalifa-Caspi, Vered; Christin-Maitre, Sophie; Vaiman, Daniel; Levi, Giovanni; Veitia, Reiner A.; Fellous, Marc

2012-01-01

20

Nonsense mutation in MERTK causes autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family  

Microsoft Academic Search

BackgroundRetinitis pigmentosa (RP) is one of the most common ophthalmic disorders affecting one in approximately 5000 people worldwide. A nuclear family was recruited from the Punjab province of Pakistan to study the genetic basis of autosomal recessive RP.MethodsAll affected individuals underwent a thorough ophthalmic examination and the disease was characterised based upon results for fundus photographs and electroretinogram recordings. Genomic

Amber Shahzadi; S Amer Riazuddin; Shahbaz Ali; David Li; Shaheen N Khan; Tayyab Husnain; Javed Akram; Paul A Sieving; J Fielding Hejtmancik; Sheikh Riazuddin

2010-01-01

21

Nonsense mutation in MERTK causes autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family  

PubMed Central

Background Retinitis pigmentosa (RP) is one of the most common ophthalmic disorders affecting one in approximately 5000 people worldwide. A nuclear family was recruited from the Punjab province of Pakistan to study the genetic basis of autosomal recessive RP. Methods All affected individuals underwent a thorough ophthalmic examination and the disease was characterised based upon results for fundus photographs and electroretinogram recordings. Genomic DNA was extracted from peripheral leucocytes. Exclusion studies were performed with short tandem repeat (STR) markers flanking reported autosomal recessive RP loci. Haplotypes were constructed and results were statistically evaluated. Results The results of exclusion analyses suggested that family PKRP173 was linked to chromosome 2q harbouring mer tyrosine kinase protooncogene (MERTK), a gene previously associated with autosomal recessive RP. Additional STR markers refined the critical interval and placed it in a 13.4 cM (17 Mb) region flanked by D2S293 proximally and D2S347 distally. Significant logarithm of odds (LOD) scores of 3.2, 3.25 and 3.18 at ?=0 were obtained with markers D2S1896, D2S2269 and D2S160. Sequencing of the coding exons of MERTK identified a mutation, c.718G?T in exon 4, which results in a premature termination of p.E240X that segregates with the disease phenotype in the family. Conclusion Our results strongly suggest that the nonsense mutation in MERTK, leading to premature termination of the protein, is responsible for RP phenotype in the affected individuals of the Pakistani family.

Shahzadi, Amber; Riazuddin, S Amer; Ali, Shahbaz; Li, David; Khan, Shaheen N; Husnain, Tayyab; Akram, Javed; Sieving, Paul A; Hejtmancik, J Fielding; Riazuddin, Sheikh

2012-01-01

22

Non-progressive cerebellar ataxia, aplasia of pupillary zone of iris, and mental subnormality (Gillespie's syndrome) affecting 3 members of a non-consanguineous family in 2 generations.  

PubMed Central

A family is reported in which a brother and sister both showed non-progressive cerebellar ataxia, aplasia of the pupillary zone of the iris, and mild mental subnormality. These clinical findings were similar to those in two previous case reports. Despite the birth of an affected son to the affected sister, this family is considered to confirm autosomal recessive inheritance of this syndrome. The paternity of the mother's husband is supported by blood groups and biochemical markers and it is presumed that the husband is a heterozygote, even though no consanguinity could be detected. Images

Crawfurd, M D; Harcourt, R B; Shaw, P A

1979-01-01

23

Bloom Syndrome: An Analysis of Consanguineous Families Assigns the Locus Mutated to Chromosome Band 15q26.1  

Microsoft Academic Search

By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous,

James German; Anne Marie Roe; Mark F. Leppert; Nathan A. Ellis

1994-01-01

24

A Novel Mutation in FGD4/FRABIN Causes Charcot Marie Tooth Disease Type 4H in Patients from a Consanguineous Tunisian Family.  

PubMed

Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically heterogeneous group of hereditary neuropathies characterized by progressive muscular and sensory loss in the distal extremities with chronic distal weakness, deformation of the feet, and loss of deep tendon reflexes. CMT4H is an autosomal recessive demyelinating subtype of CMT, due to mutations in FGD4/FRABIN, for which nine mutations are described to date. In this study, we describe three patients from a consanguineous Tunisian family, presenting with severe, early onset, slowly progressive, autosomal recessive demyelinating CMT, complicated by mild to severe kyphoscoliosis, consistent with CMT4H. In these patients, we report the identification of a novel homozygous frameshift mutation in FGD4: c.514_515insG; p.Ala172Glyfs*27. Our study reports the first mutation identified in FGD4 in Tunisian patients affected with CMT. It further confirms the important clinical heterogeneity observed in patients with mutations in FGD4 and the lack of phenotype/genotype correlations in CMT4H. Our results suggest that FGD4 should be screened in other early-onset CMT subtypes, regardless of the severity of the phenotype, and particularly in patients of consanguineous descent. In Tunisians, as in other populations with high consanguinity rates, screening of genes responsible for rare autosomal recessive CMT subtypes should be prioritized. PMID:23550889

Boubaker, Chokri; Hsairi-Guidara, Inès; Castro, Christel; Ayadi, Ines; Boyer, Amandine; Kerkeni, Emna; Courageot, Joël; Abid, Imen; Bernard, Rafaëlle; Bonello-Palot, Nathalie; Kamoun, Fatma; Cheikh, Hassen Ben; Lévy, Nicolas; Triki, Chahnez; Delague, Valérie

2013-04-01

25

A novel splice site mutation of CDHR1 in a consanguineous Israeli Christian Arab family segregating autosomal recessive cone-rod dystrophy  

PubMed Central

Purpose To investigate the genetic basis for autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. Methods Patients underwent a detailed ophthalmic examination, including funduscopy, electroretinography (ERG), visual field testing, and optical coherence tomography. Genome-wide homozygosity mapping using a single nucleotide polymorphism array was performed to identify homozygous regions shared between the two affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico analysis was used to predict the effect of the mutation on splicing. Results The family included two affected individuals. Clinical findings included progressive deterioration of visual acuity, photophobia, defective color vision, loss of central visual fields, pigmentary deposits localized mainly in the peripheral retina, a thinned and atrophic macular region, retinal vessel attenuation, absent ERG cone responses, and reduced ERG rod responses. Homozygosity mapping revealed several homozygous intervals shared among the affected individuals. One, a 12Mb interval on chromosome 10, included the CDHR1 gene. Direct sequencing revealed a single base transversion, c.1485+2T>G, located in the conserved donor splice site of Intron 13. This mutation cosegregated with the disease in the family, and was not detected in 208 Israeli Christian Arab control chromosomes. In silico analysis predicted that this mutation eliminates the Intron 13 donor splice site. Conclusions Only three distinct pathogenic mutations of CDHR1 have been reported to date in patients with autosomal recessive retinal degeneration. Here we report a novel splice site mutation of CDHR1, c.1485+2T>G, underlying autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. This report expands the spectrum of pathogenic mutations of the CDHR1 gene.

Cohen, Ben; Chervinsky, Elena; Jabaly-Habib, Haneen; Shalev, Stavit A.; Briscoe, Daniel

2012-01-01

26

Bloom syndrome: An analysis of consanguineous families assigns the locus mutated to chromosome band 15q26. 1  

SciTech Connect

By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous far more often than expected (P < 0.0001 by x[sup 2]). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a [open quotes]reverse[close quotes] genetics definition of the primary defect in Bloom syndrome.

German, J.; Roe, A.M.; Ellis, N.A. (New York Blood Center, NY (United States)); Leppert, M.F. (Univ. of Utah, Salt Lake City, UT (United States))

1994-07-05

27

Consanguinity decreases risk of breast cancer--cervical cancer unaffected.  

PubMed

Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring of consanguineous and non-consanguineous parents. Study was done prospectively in the United Arab Emirates. Selected were married female citizens, ages 40-65, who attended 12 primary health care clinics for whatever reason. In a face-to-face interview, subjects were asked: (a) about consanguineous marriages in family; (b) if they have or have had breast or cervical cancer; (c) about family history of cancer, cancer screening and other parameters. Tumour diagnosis was confirmed by review of medical records. Of 1750 women invited into study, 1445 (79%) could be used in analysis. Among 579 (40%) women of consanguineous and 866 (60%) of non-consanguineous parents there were 24 and 54 with breast cancer, respectively (RR = 0.66, CI 0.42 - 1.06). In the 40 to 50 age group, breast cancer reported 13 of 446 women of consanguineous and 37 of 633 of non-consanguineous parents (RR = 0.50, Cl 0.27 - 0.93). Cervical cancer had 15 women in consanguineous and 32 in non-consanguineous group (RR = 0.70, Cl 0.38 - 1.28). Number of families with history of breast cancer in consanguineous and non-consanguineous group was 21 and 23, respectively (P = 0.29). The cancer screening rates and other variable values had fairly balanced distribution between the 2 groups. Having consanguineous parents decreases the risk of breast cancer especially in younger women, risk of cervical cancer being unaffected. PMID:11742487

Denic, S; Bener, A

2001-11-30

28

Consanguinity decreases risk of breast cancer - cervical cancer unaffected  

PubMed Central

Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring of consanguineous and non-consanguineous parents. Study was done prospectively in the United Arab Emirates. Selected were married female citizens, ages 40–65, who attended 12 primary health care clinics for whatever reason. In a face-to-face interview, subjects were asked: (a) about consanguineous marriages in family; (b) if they have or have had breast or cervical cancer; (c) about family history of cancer, cancer screening and other parameters. Tumour diagnosis was confirmed by review of medical records. Of 1750 women invited into study, 1445 (79%) could be used in analysis. Among 579 (40%) women of consanguineous and 866 (60%) of non-consanguineous parents there were 24 and 54 with breast cancer, respectively (RR = 0.66, CI 0.42?–?1.06). In the 40 to 50 age group, breast cancer reported 13 of 446 women of consanguineous and 37 of 633 of non-consanguineous parents (RR = 0.50, Cl 0.27?–?0.93). Cervical cancer had 15 women in consanguineous and 32 in non-consanguineous group (RR = 0.70, Cl 0.38?–?1.28). Number of families with history of breast cancer in consanguineous and non-consanguineous group was 21 and 23, respectively (P = 0.29). The cancer screening rates and other variable values had fairly balanced distribution between the 2 groups. Having consanguineous parents decreases the risk of breast cancer especially in younger women, risk of cervical cancer being unaffected. © 2001 Cancer Research Campaign http://www.bjcancer.com

Denic, S; Bener, A

2001-01-01

29

Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy  

Microsoft Academic Search

Summary We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course.

S. N. Illarioshkin; I. A. Ivanova-Smolenskaya; H. Tanaka; N. V. Vereshchagin; E. D. Markova; V. V. Poleshchuk; S. M. Lozhnikova; V. S. Sukhorukov; S. A. Limborska; P. A. Slominsky; K. B. Bulayeva; S. Tsuji

1996-01-01

30

From "New Genetics" to Everyday Knowledge: Ideas about How Genetic Diseases Are Transmitted in Two Large Brazilian Families  

ERIC Educational Resources Information Center

|This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected…

Santos, Silvana; Bizzo, Nelio

2005-01-01

31

Consanguineous marriages in Morocco and the consequence for the incidence of autosomal recessive disorders.  

PubMed

Consanguineous marriage is traditionally common throughout Arab countries. This leads to an increased birth prevalence of infants with recessive disorders, congenital malformations, morbidity and mortality. The aim of this study was to evaluate the rate of consanguineous marriage in families with autosomal recessive diseases, and to compare it with the average rate of consanguinity in the Moroccan population. The study was conducted in the Department of Medical Genetics in Rabat on 176 families with autosomal recessive diseases diagnosed and confirmed by clinical, radiological, enzymatic or molecular investigations. The rate of consanguinity was also studied in 852 families who had infants with trisomy 21 confirmed by karyotyping. These families were chosen because: (i) there is no association between trisomy 21 and consanguinity, (ii) these cases are referred from different regions of Morocco and (iii) they concern all social statuses. Among 176 families with autosomal recessive disorders, consanguineous marriages comprised 59.09% of all marriages. The prevalence of consanguinity in Morocco was found to be 15.25% with a mean inbreeding coefficient of 0.0065. The differences in the rates of consanguineous marriages were highly significant when comparing the general population and couples with offspring affected by autosomal recessive conditions. These results place Morocco among the countries in the world with high rates of consanguinity. Autosomal recessive disorders are strongly associated with consanguinity. This study better defines the health risks associated with consanguinity for the development of genetic educational guidelines targeted at the public and the health sector. PMID:19433002

Jaouad, I Cherkaoui; Elalaoui, S Chafaï; Sbiti, A; Elkerh, F; Belmahi, L; Sefiani, A

2009-05-12

32

Molecular characterisation of congenital glaucoma in a consanguineous Canadian community: a step towards preventing glaucoma related blindness  

Microsoft Academic Search

Glaucoma is a leading cause of irreversible blindness in Canada. Congenital glaucoma usually manifests during the first years of life and is characterised by severe visual loss and autosomal recessive inheritance. Two disease loci, on chromosomes 1p36 and 2p21, have been associated with various forms of congenital glaucoma. A branch of a large six generation family from a consanguineous Amish

S Nicole Martin; Joanne Sutherland; Alex V Levin; Robert Klose; Megan Priston; Elise Héon

2000-01-01

33

Organ donation consanguinity or universality.  

PubMed

1. Neither the "Diseased Persons" nor the "Genetic Relations" provide an answer to "trading" in human body parts. 2. Live human body constitutes a vital source of supply of organs and tissues and the possibilities of optimum utilisation should be explored. 3. There is no scope for dogmatic postures and open-mindedness should be the approach while dealing with the issue of Organ Transplantation. 4. Society owes a duty to save the file of a dying man and in the event of failure to do so, it is absolutely immoral to interfere with his own arrangements by making unrealistic laws. No immorality is involved if an individual disposes of his spare body parts for a valid consideration to a needy person. 5. The scarcity needs to be urgently overcome otherwise unwarranted trade and crime are liable to thrive. 6. Families are not unconnected or antagonistic fragments of humanity. After thousands of years of continuous efforts the individuals on this earth have attained the stage of organic and functional integration. Atomisation of society on the basis of consanguineous proximities amounts to reversing this holistic trend. Organ transplantation is a functional expression of a highly evolved pursuit with inherent and intimate interaction in the form of organic exchange at the individual level, independent of consanguineous inducements or motivations. As such there is absolutely no scope for restricting organ donations by strangers. 7. Commercialisation should be curbed by making the enforcement agencies more efficient and not by depriving a needy person of his genuine requirements. Legislative craftsmanship lies in providing an answer without curtailing the freedom of the people. PMID:8692005

Kishore, R R

1996-01-01

34

Consanguinity and reproductive health among Arabs  

Microsoft Academic Search

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically

Ghazi O Tadmouri; Pratibha Nair; Tasneem Obeid; Mahmoud T Al Ali; Najib Al Khaja; Hanan A Hamamy

2009-01-01

35

Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus  

PubMed Central

Congenital nystagmus (NYS) is characterized by bilateral, spontaneous, and involuntary movements of the eyeballs that most commonly presents between 2 and 6 months of life. To date, 44 different FRMD7 gene mutations have been found to be etiological factors for the NYS1 locus at Xq26-q27. The aim of this study was to find the FRMD7 gene mutations in a large eleven-generation Indian pedigree with 71 members who are affected by NYS. Mutation analysis of the entire coding region and splice junctions of the FRMD7 gene revealed a novel missense mutation, c.A917G, predicts a substitution of Arg for Gln at codon 305 (Q305R) within exon 10 of FRMD7. The mutation was detected in hemizygous males, and in homozygous and heterozygous states in affected female members of the family. This mutation was not detected in unaffected members of the family or in 100 unrelated control subjects. This mutation was found to be at a highly conserved residue within the FERM-adjacent domain in affected members of the family. Structure prediction and energetic analysis of wild-type FRMD7 compared with mutant (Q305R) revealed that this change in amino acid led to a change in secondary structure predicted to be an energetically unstable protein. The present study represents the first confirmation of FRMD7 gene mutations in a multigenerational Indian family and expands the mutation spectrum for this locus.

Radhakrishna, Uppala; Ratnamala, Uppala; Deutsch, Samuel; Bartoloni, Lucia; Kuracha, Murali R; Singh, Raminder; Banwait, Jasjit; Bastola, Dhundy K; Johar, Kaid; Nath, Swapan K; Antonarakis, Stylianos E

2012-01-01

36

On Some Novel Aspects of Consanguineous Marriages  

Microsoft Academic Search

Consanguineous marriages, often viewed as incestuous and objectionable, are more widespread than commonly perceived. They integrate multiple facets of human adaptation: economic, cultural and genetic. The widely touted explanation for the origin and persistence of consanguinity is that it provides many socioeconomic benefits; however, this view may be too simplistic. The bias against consanguinity may preclude an objective understanding of

S. Denic; N. Nagelkerke; M. M. Agarwal

2011-01-01

37

Consanguinity and reproductive health among Arabs.  

PubMed

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity. PMID:19811666

Tadmouri, Ghazi O; Nair, Pratibha; Obeid, Tasneem; Al Ali, Mahmoud T; Al Khaja, Najib; Hamamy, Hanan A

2009-10-08

38

Consanguinity and reproductive health among Arabs  

PubMed Central

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity.

Tadmouri, Ghazi O; Nair, Pratibha; Obeid, Tasneem; Al Ali, Mahmoud T; Al Khaja, Najib; Hamamy, Hanan A

2009-01-01

39

A Community Genetics Perspective on Consanguineous Marriage  

Microsoft Academic Search

Consanguineous marriage has long been a controversial topic, with particular attention focused on adverse health outcomes. Unfortunately, the studies that have been conducted on consanguinity to date have usually lacked control for important sociodemographic variables, such as maternal age and birth intervals, and in estimating specific disease gene frequency, they have ignored the influence of population sub-division. Inadequate attention has

A. H. Bittles

2008-01-01

40

Consanguinity and Birth Defects in the Jerusalem Perinatal Study Cohort  

PubMed Central

Background While parental consanguinity is known to increase the risk of birth defects in offspring, it is hard to quantify this risk in populations where consanguinity is prevalent. Methods To support ongoing studies of cancer and of psychiatric disease, we studied relationships of consanguinity to 1,053 major birth defects in 29,815 offspring, born in 1964–1976. To adjust for confounding variables (geographic origin, social class and hospital), we constructed logistic regression models, using GEE to take into account correlations between sibs. Odds ratios (ORs) and 95% confidence limits were estimated in comparison to a reference group of offspring with grandfathers born in different countries. Results With 10.1% of offspring having consanguineous parents, the adjusted OR for major birth defect was 1.41 (1.12–1.74). Offspring of marriages between uncles-nieces, first cousins and more distant relatives showed adjusted ORs of 2.36 (0.98–5.68), 1.59 (1.22–2.07) and 1.20 (0.89–1.59) respectively. For descendents of grandfathers born in the same country, but not known to be related, the OR was 1.05 (0.91–1.21); these showed increased risk associated with ancestries in Western Asia (1.27, 1.04–1.55, p < 0.02) or Europe (1.13, 0.79–1.80). Conclusions A strong association of consanguinity with poverty and low education points to the need to avoid exposure to environmental hazards in these families.

Harlap, S.; Kleinhaus, K.; Perrin, M.C.; Calderon-Margalit, R.; Paltiel, O.; Deutsch, L.; Manor, O.; Tiram, E.; Yanetz, R.; Friedlander, Y.

2008-01-01

41

Consanguinity and prereproductive mortality in the Utah Mormon population.  

PubMed

To test the effects of parental consanguinity on mortality among offspring, inbreeding coefficients were estimated for 303,675 members of the Utah Mormon population who were born between 1847 and 1945. Although consanguinity has been relatively rare in this population, the large sample size permitted the identification of more than 3,500 inbred offspring. Among the offspring of unrelated parents, 13.2% died before the age of 16. Significant elevations in prereproductive mortality were seen among the offspring of first-cousin marriages (22%) and among the offspring of closer unions (32%). The cor- responding relative risks are 1.70 (95% confidence limits = 1.52, 1.91) and 2.41 (95% confidence limits = 1.59, 3.41), respectively. Other categories of relationship did not produce significant elevations in offspring mortality. Similar results were obtained when a case-control approach was used to remove the effects of socioeconomic variation. Consistent with many other studies of populations with low consanguinity rates, this population experienced a relatively high absolute increase in mortality among the offspring of first-cousin marriages (9%). Preliminary evidence is offered for the hypothesis that mortality differentials are larger in populations with low inbreeding and low mortality because nongenetic causes of death do not obscure the effects of consanguinity. PMID:11474206

Jorde, L B

2001-01-01

42

Race, consanguinity and social features in Birmingham babies: a basis for prospective study  

Microsoft Academic Search

STUDY OBJECTIVE--The aim of the study was to investigate the influence of consanguinity on children's health. DESIGN--The study is a prospective survey from birth to five years of a cohort of babies born in a multiracial community. This report details the initial findings on consanguinity. SETTING--Participating families live predominantly in three health districts of Birmingham, and were recruited in three

S Bundey; H Alam; A Kaur; S Mir; R J Lancashire

1990-01-01

43

Bleeding disorders in the tribe: result of consanguineous in breeding  

PubMed Central

Objective To determine the frequency and clinical features of bleeding disorders in the tribe as a result of consanguineous marriages. Design Cross Sectional Study Introduction Countries in which consanguinity is a normal practice, these rare autosomal recessive disorders run in close families and tribes. Here we describe a family, living in village Ali Murad Chandio, District Badin, labeled as haemophilia. Patients & Methods Our team visited the village & developed the pedigree of the whole extended family, up to seven generations. Performa was filled by incorporating patients, family history of bleeding, signs & symptoms, and bleeding from any site. From them 144 individuals were screened with CBC, bleeding time, platelet aggregation studies & RiCoF. While for PT, APTT, VWF assay and Factor VIII assay, samples were kept frozen at -70 degrees C until tested. Results The family tree of the seven generations comprises of 533 individuals, 63 subjects died over a period of 20 years and 470 were alive. Out of all those 144 subjects were selected on the basis of the bleeding history. Among them 98(68.1%) were diagnosed to have a bleeding disorder; 44.9% patients were male and 55.1% patients were female. Median age of all the patients was 20.81, range (4 months- 80 yrs). The results of bleeding have shown that majority had gum bleeding, epistaxis and menorrhagia. Most common bleeding disorder was Von Willebrand disease and Platelet functional disorders. Conclusion Consanguineous marriages keep all the beneficial and adversely affecting recessive genes within the family; in homozygous states. These genes express themselves and result in life threatening diseases. Awareness, education & genetic counseling will be needed to prevent the spread of such common occurrence of these bleeding disorders in the community.

2010-01-01

44

Consanguineous marriage and reproduction in Beirut, Lebanon.  

PubMed Central

Effects of consanguineous marriages on couples' fertility and on offspring mortality were investigated in Beirut through a population-based health survey of 2,752 households. A multistage random sampling procedure was used, and information was obtained from all ever-married women in the household about their reproductive performance and genealogical relationship with spouse; demographic and socioeconomic information was also recorded. Twenty-five percent of all marriages were between relatives, and the spouses were first cousins in approximately 57% of all consanguineous marriages. Total pregnancies, live births, and living children were significantly higher among consanguineous couples than among nonconsanguineous ones, as was the proportion dead among children ever born. However, no difference remained in either fertility or mortality, when allowance was made for socioeconomic status, religious affiliation, and marriage duration. The issue of confounding is discussed, and the lack of significant pattern in the final analysis is interpreted as resulting from a long-term practice of consanguineous marriages.

Khlat, M

1988-01-01

45

Association among Education Level, Occupation Status, and Consanguinity in Tunisia and Croatia  

PubMed Central

Aim To investigate the association between education level, occupation status (a proxy for socio-economic status), and consanguinity in 2 large data sets from Tunisia and Croatia countries with different attitudes toward consanguinity. Methods The sample of 1016 students, attending 5 university institutions in Monastir, Tunisia, were interviewed about the educational level and occupation status of their parents and the degree of parental relatedness. In Croatia, a sample of 1001 examinees from 9 isolated island populations was interviewed about their own educational level, occupation status, and consanguinity. Results Prevalence of consanguinity (offspring of second cousins or closer) among 1016 Tunisian students was 20.1%, and 9.3% among 1001 Croatian isolates. In Tunisia, the association between consanguinity and both parental degree of education and parental occupation status was highly significant in women (P<0.001), but not significant in men. In Croatia, no statistically significant associations were noted, although there was a consistent trend of increased prevalence of consanguinity with lower education level or occupation status in both genders, but more pronounced in women. Conclusion Association between education level, socio-economic status, and consanguinity needs to be taken into account in inbreeding studies in human populations. The relationship may be specific for each studied population and highly dependent on the cultural context. It is generally more pronounced among women in most settings.

Kerkeni, Emna; Monastiri, Kamel; Saket, Besma; Rudan, Diana; Zgaga, Lina; Ben Cheikh, Hassen

2006-01-01

46

Spectrum of malformations of the hindbrain (cerebellum, pons, and medulla) in a cohort of children with high rate of parental consanguinity  

Microsoft Academic Search

We review 25 patients with a spectrum of hind- brain (cerebellum, pons, and medulla) malforma- tions from a cohort of children with high parental consanguinity rate. Twenty-three of the 25 pa- tients were born to consanguineous parents. The patients were classified in four groups. Eleven patients of 6 families had malformation of the hindbrain and midbrain with molar tooth sign

László Sztriha; Johan G. Johansen

2005-01-01

47

Large Constituent Families Help Children Parse Compounds  

ERIC Educational Resources Information Center

|The family size of the constituents of compound words, or the number of compounds sharing the constituents, has been shown to affect adults' access to compound words in the mental lexicon. The present study was designed to see if family size would affect children's segmentation of compounds. Twenty-five English-speaking children between 3;7 and…

Krott, Andrea; Nicoladis, Elena

2005-01-01

48

Assessment of Association between Consanguinity and Fertility in Asian Populations  

Microsoft Academic Search

Although a high proportion of marriages in Asia are consanguineous (i.e. contracted between close biological relatives), with some notable exceptions, there is a dearth of demographic and anthropological literature on the association between consanguinity and fertility. This paper presents an overview of the prevalence of consanguineous marriages in selected South and Southeast Asian countries, followed by an assessment of the

Rafat Hussain; Alan H. Bittles

2004-01-01

49

Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy.  

PubMed

We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course. The second group included three patients with a slowly progressive distal myopathy first manifested in the late teens and confined to the tibial and calf muscles. Each of these two phenotypes segregated independently as an autosomal recessive trait, and muscle biopsies showed non-specific myopathic changes. Lastly, two male siblings exhibited an atypical variant of Duchenne muscular dystrophy confirmed by detection of a deletion in the dystrophin gene. To clarify the molecular basis of the polymorphic autosomal recessive form of muscular dystrophy in this kindred, we performed molecular genetic studies on 67 family members and obtained significant evidence for linkage to chromosome 2p. A maximum pairwise lod (logarithm of odds) score of 5.64 was achieved at the zero recombination fraction (i.e. at theta = 0.00) for locus D2S291; multipoint linkage analysis confirmed the most likely location of a mutant gene near D2S291. The patients with LGMD and those with the distal muscular dystrophy phenotype share a common affected homozygous haplotype associated with the same founder chromosome; key recombinants defined D2S286 and D2S292 to be the closest loci flanking the mutant gene. Remarkably, two clinically distinct forms of autosomal recessive muscular dystrophy, LGMD type 2B (LGMD2B) and Miyoshi myopathy, were recently mapped to the same locus. We suggest that all three chromosome 2p-linked conditions may represent allelic disorders, i.e. different phenotypic expressions of a single gene. PMID:9009996

Illarioshkin, S N; Ivanova-Smolenskaya, I A; Tanaka, H; Vereshchagin, N V; Markova, E D; Poleshchuk, V V; Lozhnikova, S M; Sukhorukov, V S; Limborska, S A; Slominsky, P A; Bulayeva, K B; Tsuji, S

1996-12-01

50

Endogamy, consanguinity and community genetics  

Microsoft Academic Search

The population of India is composed of many thousands of subpopulations, divided by geography, language, religion and caste or biraderi (patrilineage) boundaries, with endogamous marriage the norm. The net effect has been the creation of multiple genetic isolates with indi- vidual mutation profiles, but to date the clinical con- sequences of this highly complex differentiation have been largely ignored. In

A. H. BITTLES

2003-01-01

51

Endogamy, consanguinity and community genetics  

Microsoft Academic Search

The population of India is composed of many thousands of subpopulations, divided by geography, language, religion and caste\\u000a or biraderi (patrilineage) boundaries, with endogamous marriage the norm. The net effect has been the creation of multiple\\u000a genetic isolates with individual mutation profiles, but to date the clinical consequences of this highly complex differentiation\\u000a have been largely ignored. In contrast, the

Alan Bittles

2002-01-01

52

Socioeconomic, demographic and legal influences on consanguinity and kinship in northern coastal Sweden 1780-1899.  

PubMed

Most studies on consanguinity have been conducted on contemporary populations and have focused on the prevalence and types of preferred intra-familial marriage. With its comprehensive birth, marriage and deaths records dating back to the late 17th century, and the legal bar on first cousin marriage removed in the mid-19th century, Sweden offers unique opportunities to examine the factors that determine by whom, where and why consanguineous marriages were contracted. The present study covers the period 1780-1899 and presents a detailed portrait of cousin and sibling exchange marriages in the Skellefteå region of northern coastal Sweden. The combined prevalence of first, second and third cousin marriage increased from 2.3% in 1790-1810 to 8.8% in 1880-1899, and multi-generation consanguinity also increased significantly over the study period. The distribution and prevalence of first cousin marriages was strikingly non-random, with a significantly greater propensity for consanguinity among land-owning families, especially involving first-born sons, within specific pedigrees, and in a number of more remote inland communities. Additional factors associated with a greater likelihood of consanguineous marriage included physical or mental disability among males, and among females the prior birth of an illegitimate child. Besides the inherent interest in the social and demographic structure of this region of northern Sweden during the course of the 19th century, in future studies it will be important to determine the degree to which the observed patterns of consanguineous and sibling exchange marriages in these past generations could have influenced present-day genetic structure. PMID:21418728

Egerbladh, I; Bittles, A H

2011-03-22

53

A silent revolution: The internationalisation of large Spanish family firms  

Microsoft Academic Search

This article studies the dominant role played by large family firms in the internationalisation of the Spanish economy. Based on new empirical evidence from circa 150 historical and internationalised family firms, the article integrates concepts and theories from recent literature on internationalisation, international entrepreneurship, sociology, and family business. The main argument is that in Spain, as in other European, South

Nuria Puig; Paloma Fernández Pérez

2009-01-01

54

Birth Defects and Parental Consanguinity in Norway  

Microsoft Academic Search

The study compares frequencies of birth defects between immigrant groups and the rest of the Norwegian population in Norway and estimates the influence of consanguinity and socioeconomic factors on these frequencies. The authors studied all 1.56 million births in Norway from 1967 to 1993. Of these, 7,494 children had two Pakistani parents, 84,688 had one Norwegian and one immigrant parent,

Camilla Stoltenberg; Per Magnus; Rolv Terje Lie; Anne Kjersti Daltveit; Lorentz M. Irgens

55

[Nephrogenic diabetes insipidus in a large family].  

PubMed

Hereditary nephrogenic diabetes insipidus is a rare disease. We describe here three brothers with this disease from a big family consisting of 10 siblings. The case is undoubtedly X-linked because the sufferers are only boys, one of them with a different father. The illness was noticed rather late, namely, at the ages of approximately 7, 6 and 5 years. Possibly, this is a particular characteristic of this family, because the disease is usually diagnosed before the age of two years. In the oldest brother (at present 15 years old) epicystotomy was performed at the time of diagnosis because of polyuria, hydroureteronephrosis and bladder hypotonia; the intervention caused a urinary tract infection leading to chronic pyelonephritis and renal scarring. No urologic intervention was necessary in the younger brothers, because their illness was noticed and treatment started somewhat earlier. This case shows that polydipsia and polyuria should always be assessed properly to disclose their causes. PMID:16528130

Kaltenis, Petras; Jankauskiene, Augustina

2006-01-01

56

A new locus for autosomal recessive limb-girdle muscular dystrophy in a large consanguineous Tunisian family maps to chromosome 19q13.3  

Microsoft Academic Search

Autosomal recessive limb-girdle muscular dystrophies represent a genetically heterogeneous group of diseases characterized by a progressive involvement of skeletal muscles. They show a wide spectrum of clinical courses, varying from very mild to severe. Eight loci responsible for autosomal recessive limb-girdle muscular dystrophies have been mapped and six defective genes identified. In this study, we report the clinical data, muscle

A. Driss; R. Amouri; C. Ben Hamida; S. Souilem; N. Gouider-Khouja; M. Ben Hamida; F. Hentati

2000-01-01

57

Consanguinity and Birth Defects in the Jerusalem Perinatal Study Cohort  

Microsoft Academic Search

Background: While parental consanguinity is known to increase the risk of birth defects in offspring, it is hard to quantify this risk in populations where consanguinity is prevalent. Methods: To support ongoing studies of cancer and of psychiatric disease, we studied relationships of consanguinity to 1,053 major birth defects in 29,815 offspring, born in 1964–1976. To adjust for confounding variables

S. Harlap; K. Kleinhaus; M. C. Perrin; R. Calderon-Margalit; O. Paltiel; L. Deutsch; O Manor; E. Tiram; R. Yanetz; Y. Friedlander

2008-01-01

58

The Large Poor Family-a Housing GAP.  

National Technical Information Service (NTIS)

In the seven cities studied, 103,000 large families had incomes so low that they were unable to afford decent private housing. Public programs provide housing for only 20,000 of these families, leaving a shortage of 83,000 units. If all 12,000 units now p...

W. Smart W. Rybeck H. E. Shuman

1968-01-01

59

Institutions Behind Family Ownership and Control in Large Firms  

Microsoft Academic Search

abstract There is a major debate regarding the role of concentrated family ownership and control in large firms, with three positions suggesting that such concentration is (1) good, (2) bad, or (3) irrelevant for firm value. Why are there such differences? We theorize that the impact of family ownership and control on firm value is associated with the level of

Mike W. Peng; Yi Jiang

2010-01-01

60

Little Brother Joins the Large Family  

NASA Astrophysics Data System (ADS)

On the night of 15 December 2006, the fourth and last-to-be-installed VLTI Auxiliary Telescope (AT4) obtained its 'First Light'. The first images demonstrate that AT4 will be able to deliver the excellent image quality already delivered by the first three ATs. It will soon join its siblings to perform routinely interferometric measurements. ESO PR Photo 51a/06 ESO PR Photo 51a/06 VLT Auxiliary Telescope The VLT is composed of four 8.2-m Unit Telescope (Antu, Kueyen, Melipal and Yepun). They have been progressively put into service together with a vast suite of the most advanced astronomical instruments and are operated every night in the year. Contrary to other large astronomical telescopes, the VLT was designed from the beginning with the use of interferometry as a major goal. The VLT Interferometer (VLTI) combines starlight captured by two or three 8.2- VLT Unit Telescopes, dramatically increasing the spatial resolution and showing fine details of a large variety of celestial objects. ESO PR Photo 51b/06 ESO PR Photo 51b/06 One AT Under the Sky However, most of the time the large telescopes are used for other research purposes. They are therefore only available for interferometric observations during a limited number of nights every year. Thus, in order to exploit the VLTI each night and to achieve the full potential of this unique setup, some other (smaller), dedicated telescopes were included into the overall VLT concept. These telescopes, known as the VLTI Auxiliary Telescopes (ATs), are mounted on tracks and can be placed at precisely defined "parking" observing positions on the observatory platform. From these positions, their light beams are fed into the same common focal point via a complex system of reflecting mirrors mounted in an underground system of tunnels. The Auxiliary Telescopes are real technological jewels. They are placed in ultra-compact enclosures, complete with all necessary electronics, an air conditioning system and cooling liquid for thermal control, compressed air for enclosure seals, a hydraulic plant for opening the dome shells, etc. Each AT is also fitted with a transporter that lifts the telescope and relocates it from one station to another. It moves around with its own housing on the top of Paranal, almost like a snail. The VLTI is arguably the world's most advanced optical device of this type. It has already demonstrated its powerful capabilities by addressing several key scientific issues, such as determining the size and the shape of a variety of stars (ESO PR 22/02, PR 14/03, PR 31/03, and PR 09/06), measuring distances to stars (ESO PR 25/04), probing the innermost regions of the proto-planetary discs around young stars (ESO PR 27/04 and PR 35/06) or making the first detection by infrared interferometry of an extragalactic object (ESO PR 17/03).

2006-12-01

61

The changing profile of consanguinity rates in Bahrain, 1990-2009.  

PubMed

Consanguineous marriage is traditional and respected in most communities of North Africa, the Middle East and West Asia, including Bahrain, with intra-familial unions accounting for 20-50+% of all marriages. Significant secular changes in consanguinity rates have been reported in recent decades in different populations. Among parents of 14,237 newborns in Bahrain in 2008-2009, the total consanguinity and first cousin marriage rates over a period of four months in 2008 were 10.9% and 6.9% respectively, while during all of 2009 the rates were 11.4% and 6.8% respectively. The study confirms that over a ten-year period first cousin marriage rates in Bahrain have declined from 24% to nearly 7%. Although advice against cousin marriages was not attempted at any stage in the comprehensive community genetics programmes in Bahrain, increasing the literacy of the public and of the health care providers on prevention strategies for genetic diseases could have contributed to this decline in consanguinity rate in Bahrain. PMID:22123433

Al-Arrayed, Shaikha; Hamamy, Hanan

2011-11-29

62

Does consanguinity lead to decreased incidence of breast cancer?  

Microsoft Academic Search

Background: In the Middle East region, consanguinity remains to be a central feature where it has shown an increasing trend. Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both environmental and genetic factors. Aim: The aim of this study was to examine the possible effect of consanguinity on the risk of

Abdulbari Bener; Hanadi Rafii El Ayoubi; Awab Ibrahim Ali; Aisha Al-Kubaisi; Haya Al-Sulaiti

2010-01-01

63

Consanguinity and the Risk of Congenital Heart Disease  

PubMed Central

Consanguineous unions have been associated with an increased susceptibility to various forms of inherited disease. Although consanguinity is known to contribute to recessive diseases, the potential role of consanguinity in certain common birth defects is less clear, particularly since the disease pathophysiology may involve genetic and environmental/epigenetic factors. In this study we ask whether consanguinity affects one of the most common birth defects, congenital heart disease, and identify areas for further research into these birth defects, since consanguinity may now impact health on a near-global basis. A systematic review of consanguinity in congenital heart disease was performed, focusing on non-syndromic disease, with the methodologies and results from studies of different ethnic populations compared. The risks for congenital heart disease have been assessed and summarized collectively and by individual lesion. The majority of studies support the view that consanguinity increases the prevalence of congenital heart disease, however the study designs differed dramatically. Only a few (n = 3) population-based studies that controlled for potential sociodemographic confounding were identified, and data on individual cardiac lesions were limited by case numbers. Overall the results suggest that the risk for congenital heart disease is increased in consanguineous unions in the studied populations, principally at first cousin level and closer, a factor that should be considered in empiric risk estimates in genetic counseling. However, for more precise risk estimates a better understanding of the underlying disease factors is needed.

Shieh, Joseph T.C.; Bittles, Alan H.; Hudgins, Louanne

2012-01-01

64

Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia  

Microsoft Academic Search

Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness.\\u000a Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms\\u000a of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP

Rebecca Schüle; Elisabeth Brandt; Kathrin N. Karle; Maria Tsaousidou; Stephan Klebe; Sven Klimpe; Michaela Auer-Grumbach; Andrew H. Crosby; Christian A. Hübner; Ludger Schöls; Thomas Deufel; Christian Beetz

2009-01-01

65

A Novel Mutation in the Sodium\\/Iodide Symporter Gene in the Largest Family with Iodide Transport Defect  

Microsoft Academic Search

We previously reported nine children with an autosomally reces- sive form of congenital hypothyroidism due to an iodide transport defect in a large Hutterite family with extensive consanguinity living in central Canada. Since the original report, we have diagnosed con- genital hypothyroidism by newborn TSH screening in 9 additional children from the family. We performed direct sequencing of the PCR

SHINJI KOSUGI; SHELLY BHAYANA; HEATHER J. DEAN

2010-01-01

66

Non-DYT1 dystonia in a large Italian family  

Microsoft Academic Search

A large non-Jewish Italian family affected by idiopathic torsion dystonia with autosomal dominant transmission and almost complete penetrance is reported. The prevalent phenotype was characterised by early onset with cranial-cervical involvement and progression to a segmental distribution; progression to generalisation was also found. Among 45 people examined, 14 were considered definitely or probably affected by idiopathic torsion dystonia. Eight definitely

A R Bentivoglio; N Del Grosso; A Albanese; E Cassetta; P Tonali; M Frontali

1997-01-01

67

Does consanguinity affect the severity of pre-eclampsia?  

Microsoft Academic Search

To determine whether consanguinity is more likely to be associated with severe forms of pre-eclampsia\\/eclampsia. Presuming a pure genetic contribution, we speculated that consanguineous marriages would increase the occurrence of severe forms of pre-eclampsia\\/eclampsia, through an expected increased chance for homozygosity to the putative gene. The study is a clinical case series on pre-eclamptic\\/eclamptic primiparae delivered at Princess Badea Teaching

Francis L. Badria; Z. O. Amarin

2003-01-01

68

Phenotypic Variation in a Large Family with Autosomal Dominant Hypocalcaemia  

Microsoft Academic Search

Background\\/Aims: Autosomal dominant hypocalcaemia (ADH) is caused by activating mutations in the calcium- sensing receptor (CASR). We aimed to describe the phenotypic variation within a large family with ADH, especially kidney and cerebral basal ganglia calcifications. Methods: Fifteen related subjects carrying the CASR mutation T151M participated in a cross-sectional study of calcium homeostasis, renal ultrasonography, cerebral CT, bone mineral density,

J. I. Sørheim; E. S. Husebye; B. G. Nedrebø; E. Svarstad; J. Lind; H. Boman; K. Løvås

2010-01-01

69

New Sequences with Low Correlation and Large Family Size  

NASA Astrophysics Data System (ADS)

In direct-sequence code-division multiple-access (DS-CDMA) communication systems and direct-sequence ultra wideband (DS-UWB) radios, sequences with low correlation and large family size are important for reducing multiple access interference (MAI) and accepting more active users, respectively. In this paper, a new collection of families of sequences of length pn-1, which includes three constructions, is proposed. The maximum number of cyclically distinct families without GMW sequences in each construction is ?(pn-1)/n·?(pm-1)/m, where p is a prime number, n is an even number, and n=2m, and these sequences can be binary or polyphase depending upon choice of the parameter p. In Construction I, there are pn distinct sequences within each family and the new sequences have at most d+2 nontrivial periodic correlation {-pm-1, -1, pm-1, 2pm-1,…,dpm-1}. In Construction II, the new sequences have large family size p2n and possibly take the nontrivial correlation values in {-pm-1, -1, pm-1, 2pm-1,…,(3d-4)pm-1}. In Construction III, the new sequences possess the largest family size p(d-1)n and have at most 2d correlation levels {-pm-1, -1,pm-1, 2pm-1,…,(2d-2)pm-1}. Three constructions are near-optimal with respect to the Welch bound because the values of their Welch-Ratios are moderate, WR_??_d, WR_??_3d-4 and WR_??_2d-2, respectively. Each family in Constructions I, II and III contains a GMW sequence. In addition, Helleseth sequences and Niho sequences are special cases in Constructions I and III, and their restriction conditions to the integers m and n, pm?2 (mod 3) and n?0 (mod 4), respectively, are removed in our sequences. Our sequences in Construction III include the sequences with Niho type decimation 3·2m-2, too. Finally, some open questions are pointed out and an example that illustrates the performance of these sequences is given.

Zeng, Fanxin

70

Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia.  

PubMed

Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP. One sporadic patient showing HSP as well as optic atrophy carried a homozygous nonsense mutation. Compound heterozygosity was observed in a recessive family with a clinically pure phenotype. A heterozygous missense change segregated in a small dominant family. We also found a significant association of a known coding polymorphism with cerebellar signs complicating a primary HSP phenotype. Our findings suggest CYP7B1 alterations to represent a rather frequent cause of HSP that should be considered in patients with various clinical presentations. PMID:18855023

Schüle, Rebecca; Brandt, Elisabeth; Karle, Kathrin N; Tsaousidou, Maria; Klebe, Stephan; Klimpe, Sven; Auer-Grumbach, Michaela; Crosby, Andrew H; Hübner, Christian A; Schöls, Ludger; Deufel, Thomas; Beetz, Christian

2008-10-15

71

Maternally inherited mitochondrial DNA disease in consanguineous families  

Microsoft Academic Search

Mitochondrial respiratory chain disease represents one of the most common inborn errors of metabolism and is genetically heterogeneous, with biochemical defects arising from mutations in the mitochondrial genome (mtDNA) or the nuclear genome. As such, inheritance of mitochondrial respiratory chain disease can either follow dominant or recessive autosomal (Mendelian) inheritance patterns, the strictly matrilineal inheritance observed with mtDNA point mutations

Charlotte L Alston; Langping He; Andrew A Morris; Imelda Hughes; Christian de Goede; Douglass M Turnbull; Robert McFarland; Robert W Taylor

2011-01-01

72

Familial interstitial pulmonary fibrosis: A large family with atypical clinical features  

PubMed Central

A large kindred of familial pulmonary fibrosis is reported. Six members from the first two generations of this particular kindred were described more than 40 years previously; six more individuals from the third and fourth generations have also been evaluated. The proband, now 23 years of age, has mild disease; the other 11 documented affected family members all died from their disease at an average age of 37 years (range 25 to 50 years). The pathology was that of usual interstitial pneumonia, as is typical in idiopathic pulmonary fibrosis. However, the initial radiographic pattern in many of these individuals was upper lobe and nodular and, along with the young age, was atypical for idiopathic pulmonary fibrosis. Several genetic abnormalities have been associated with familial pulmonary fibrosis. The present study examined the genes coding for surfactant protein-C, ATP-binding cassette protein A3 and telomerase, and found no abnormalities.

Chibbar, Ranji; Gjevre, John A; Shih, Francis; Neufeld, Heather; Lemire, Edmond G; Fladeland, Derek A; Cockcroft, Donald W

2010-01-01

73

Consanguinity and susceptibility to infectious diseases in humans  

PubMed Central

Studies of animal populations suggest that low genetic heterozygosity is an important risk factor for infection by a diverse range of pathogens, but relatively little research has looked to see whether similar patterns exist in humans. We have used microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increases risk of infection. Our results indicate that inbred individuals are more common among our infected cases for TB and hepatitis, but only in populations where consanguineous marriages are common. No effect was found either for leprosy, which is thought to be oligogenic, or for hepatitis in Italy where consanguineous marriages are rare. Our results suggest that consanguinity is an important risk factor in susceptibility to infectious diseases in humans.

Lyons, Emily J.; Frodsham, Angela J.; Zhang, Lyna; Hill, Adrian V.S.; Amos, William

2009-01-01

74

Examining BCL-2 family function with large unilamellar vesicles.  

PubMed

The BCL-2 (B cell CLL/Lymphoma) family is comprised of approximately twenty proteins that collaborate to either maintain cell survival or initiate apoptosis(1). Following cellular stress (e.g., DNA damage), the pro-apoptotic BCL-2 family effectors BAK (BCL-2 antagonistic killer 1) and/or BAX (BCL-2 associated X protein) become activated and compromise the integrity of the outer mitochondrial membrane (OMM), though the process referred to as mitochondrial outer membrane permeabilization (MOMP)(1). After MOMP occurs, pro-apoptotic proteins (e.g., cytochrome c) gain access to the cytoplasm, promote caspase activation, and apoptosis rapidly ensues(2). In order for BAK/BAX to induce MOMP, they require transient interactions with members of another pro-apoptotic subset of the BCL-2 family, the BCL-2 homology domain 3 (BH3)-only proteins, such as BID (BH3-interacting domain agonist)(3-6). Anti-apoptotic BCL-2 family proteins (e.g., BCL-2 related gene, long isoform, BCL-xL; myeloid cell leukemia 1, MCL-1) regulate cellular survival by tightly controlling the interactions between BAK/BAX and the BH3-only proteins capable of directly inducing BAK/BAX activation(7,8). In addition, anti-apoptotic BCL-2 protein availability is also dictated by sensitizer/de-repressor BH3-only proteins, such as BAD (BCL-2 antagonist of cell death) or PUMA (p53 upregulated modulator of apoptosis), which bind and inhibit anti-apoptotic members(7,9). As most of the anti-apoptotic BCL-2 repertoire is localized to the OMM, the cellular decision to maintain survival or induce MOMP is dictated by multiple BCL-2 family interactions at this membrane. Large unilamellar vesicles (LUVs) are a biochemical model to explore relationships between BCL-2 family interactions and membrane permeabilization(10). LUVs are comprised of defined lipids that are assembled in ratios identified in lipid composition studies from solvent extracted Xenopus mitochondria (46.5% phosphatidylcholine, 28.5% phosphatidylethanoloamine, 9% phosphatidylinositol, 9% phosphatidylserine, and 7% cardiolipin)(10). This is a convenient model system to directly explore BCL-2 family function because the protein and lipid components are completely defined and tractable, which is not always the case with primary mitochondria. While cardiolipin is not usually this high throughout the OMM, this model does faithfully mimic the OMM to promote BCL-2 family function. Furthermore, a more recent modification of the above protocol allows for kinetic analyses of protein interactions and real-time measurements of membrane permeabilization, which is based on LUVs containing a polyanionic dye (ANTS: 8-aminonaphthalene-1,3,6-trisulfonic acid) and cationic quencher (DPX: p-xylene-bis-pyridinium bromide)(11). As the LUVs permeabilize, ANTS and DPX diffuse apart, and a gain in fluorescence is detected. Here, commonly used recombinant BCL-2 family protein combinations and controls using the LUVs containing ANTS/DPX are described. PMID:23070252

Asciolla, James J; Renault, Thibaud T; Chipuk, Jerry E

2012-10-05

75

Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred  

PubMed Central

The biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1–13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans.

Gulsuner, Suleyman; Tekinay, Ayse Begum; Doerschner, Katja; Boyaci, Huseyin; Bilguvar, Kaya; Unal, Hilal; Ors, Aslihan; Onat, O. Emre; Atalar, Ergin; Basak, A. Nazli; Topaloglu, Haluk; Kansu, Tulay; Tan, Meliha; Tan, Uner; Gunel, Murat; Ozcelik, Tayfun

2011-01-01

76

SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly  

Microsoft Academic Search

Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family\\u000a sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of\\u000a ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based\\u000a homozygosity mapping and high-resolution microarray-based

Masoud Garshasbi; Mohammad Mahdi Motazacker; Kimia Kahrizi; Farkhondeh Behjati; Seyedeh Sedigheh Abedini; Sahar Esmaeeli Nieh; Saghar Ghasemi Firouzabadi; Christian Becker; Franz Rüschendorf; Peter Nürnberg; Andreas Tzschach; Reza Vazifehmand; Fikret Erdogan; Reinhard Ullmann; Steffen Lenzner; Andreas W. Kuss; H. Hilger Ropers; Hossein Najmabadi

2006-01-01

77

Consanguinity and complex cardiac anomalies with situs ambiguus  

Microsoft Academic Search

A survey of British born Asian and English populations of children with congenital cardiac anomalies showed an increased incidence in the Muslim Asian population of complex lesions with visceral heterotaxia. There is a very high incidence of parental consanguinity among Muslim Asian children with complex congenital cardiac anomalies that is even higher than in the general Muslim Asian population of

A R Gatrad; A P Read; G H Watson

1984-01-01

78

Identification of a novel ZNF469 mutation in a large family with Ehlers-Danlos phenotype.  

PubMed

Brittle cornea syndrome (BCS) is a genetically heterogeneous disorder characterized by extreme corneal fragility and thinning, which may lead to spontaneous or trauma-induced corneal rupture. BCS-1 and BCS-2 are caused by recessive mutations in ZNF469 and PRDM5, respectively. Both genes play a role in the regulatory pathway of corneal development and maintenance. We report a consanguineous family with five patients affected with the cardinal ocular features of BCS and significant musculoskeletal findings primarily in the form of joint hypermobility and severe kyphoscoliosis. The patients had thin velvety skin, hallux valgus, variable sensorineural hearing loss and arachnodactyly. Interestingly, one of the patients additionally had phenylketonuria and showed a milder ophthalmological and musculoskeletal phenotype than his affected siblings. The urinary pyridinoline and deoxypyridinoline concentrations and their ratios were mildly elevated indicating increased bone-collagen turnover. A novel homozygous 14 bp duplication in exon 2 of ZNF469 (c.8817_8830dup) was uncovered by direct sequencing. This family highlights the phenotypic overlap between BCS and Ehlers-Danlos syndrome. PMID:23010198

Al-Owain, Mohammed; Al-Dosari, Mohammed S; Sunker, Asma; Shuaib, Taghreed; Alkuraya, Fowzan S

2012-09-23

79

Consanguinity and other marriage market effects of a wealth shock in bangladesh.  

PubMed

This paper uses a wealth shock from the construction of a flood protection embankment in rural Bangladesh coupled with data on the universe of all 52,000 marriage decisions between 1982 and 1996 to examine changes in marital prospects for households protected by the embankment relative to unprotected households living on the other side of the river. We use difference-in-difference specifications to document that brides from protected households commanded larger dowries, married wealthier households, and became less likely to marry biological relatives. Financial liquidity-constrained households appear to use within-family marriage (in which one can promise ex-post payments) as a form of credit to meet up-front dowry demands, but the resultant wealth shock for households protected by the embankment relaxed this need to marry consanguineously. Our results shed light on the socioeconomic roots of consanguinity, which carries health risks for offspring but can also carry substantial benefits for the families involved. PMID:23619998

Mobarak, Ahmed Mushfiq; Kuhn, Randall; Peters, Christina

2013-10-01

80

Recessive versus imprinted disorder: consanguinity can impede establishing the diagnosis of autosomal dominant pseudohypoparathyroidism type Ib  

PubMed Central

Hypocalcemia and hyperphosphatemia with low/normal parathyroid hormone (PTH) levels can be observed in hypoparathyroidism (HP), a disorder that may follow an autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. Similar biochemical changes are also observed in pseudohypoparathyroidism (PHP) type Ia and Ib, but affected patients usually show elevated PTH levels indicative of hormonal resistance. Features of Albright’s hereditary osteodystrophy (AHO) are typically not observed in patients affected by familial forms of PHP-Ib, which are most frequently caused by maternally inherited, heterozygous microdeletions within STX16 and are associated with isolated loss of methylation at GNAS exon A/B. We established the molecular defect in two children of consanguineous Turkish parents, who presented with hypocalcemia, hyperphosphatemia, and low 25-OH vitamin D levels, but initially normal or only mildly elevated PTH levels, i.e. findings that do not readily exclude HP. After normalizing serum magnesium levels, hypocalcemia and hyperphosphatemia persisted, and PTH levels increased, suggesting PTH-resistance rather than PTH-deficiency. Because of the absence of AHO and parental consanguinity, an AR form of PHP-Ib appeared plausible, which had previously been suggested for sporadic cases. However, loss of GNAS methylation was restricted to exon A/B, which led to the identification of the 3-kb STX16 microdeletion. The same mutation was also detected in the healthy mother, who did not show any GNAS methylation abnormality, indicating that her deletion resides on the paternal allele. Our findings emphasize the importance of considering a parentally imprinted, autosomal dominant disorder even if consanguinity suggests an autosomal recessive mode of inheritance.

Turan, Serap; Akin, Leyla; Akcay, Teoman; Adal, Erdal; Sarikaya, Sevil; Bastepe, Murat; Juppner, Harald

2010-01-01

81

Measuring Family Outcomes Early Intervention: Findings from a Large-Scale Assessment  

ERIC Educational Resources Information Center

This article reports data from a large-scale assessment using the Family Outcomes Survey with families participating in early intervention. The study was designed to determine how families describe themselves with regard to outcomes achieved, the extent to which outcomes are interrelated, and the extent to which child, family, and program factors…

Raspa, Melissa; Bailey, Donald B., Jr.; Olmsted, Murrey G.; Nelson, Robin; Robinson, Nyle; Simpson, Mary Ellen; Guillen, Chelsea; Houts, Renate

2010-01-01

82

Genetic Counseling in Southern Iran: Consanguinity and Reason for Referral  

Microsoft Academic Search

Population based genetic counseling that promotes public health goals is an appropriate health care service. The genetic counseling\\u000a center in Shiraz, southern Iran serves most of the clients in the region. During a 4-year period, 2,686 couples presented\\u000a for genetic counseling. Data files revealed that 85% had consanguineous relationships (1.5% double first cousin, 74% first\\u000a cousin, 8% second cousin, 1.5%

Mohsen Fathzadeh; Mohammad Ali Babaie Bigi; Masood Bazrgar; Majid Yavarian; Hamid Reza Tabatabaee; Seyed Mohammad Akrami

2008-01-01

83

Familial hiatal hernia in a large five generation family confirming true autosomal dominant inheritance  

Microsoft Academic Search

BACKGROUNDFamilial hiatal hernia has only rarely been documented.AIMSTo describe the pattern of inheritance of familial hiatal hernia within an affected family.SUBJECTSThirty eight members of a family pedigree across five generations.METHODSAll family members were interviewed and investigated by barium meal for evidence of a hiatal hernia.RESULTSTwenty three of 38 family members had radiological evidence of a hiatal hernia. No individual with

I J Carré; B T Johnston; P S Thomas; P J Morrison

1999-01-01

84

Genetic counselling in family planning.  

PubMed

The family planning program is not restricted to population control; it also aims at the wider aspect of family welfare and human health. A large number of human diseases are due to genetic abnormalities. Examples are mongolism (Down's syndrome), ovarian dysgenesis (Turner's syndrome), nonfunctional testes (Klinefelter's syndrome), chronic myeloid leukemia, anemia, thalassemia, congenital malformations, and schizophrenia. Mental defects include imbeciles and the feebleminded. Constitutional diseases include diabetes, idiopathic epilepsy, pernicious anemia, and some thyroid abnormalities. Some chronic diseases also have a significant genetic component in their etiology, such as asthma and other allergies. About half of the stillbirths and embryonic wastage are suspected of being due to genetic malformations. Consanguinity has an important bearing on malformations and developmental anomalies. In India, where consanguinity is more frequent, malformations per 1000 births were 8.6 and 3.1 in 2 centers studied. Neural tube defects, harelip, cleft palate, and malformations of the gut and of limbs were prevalent. The population that needs genetic counseling is not large. Persons suffering from hereditary dise ases having a high risk of transmission should be advised to refrain fro m having children. A correct diagnosis, complete family history, and kn owledge of the literature on inherited disease is needed by the counselo rs. Family planning programs should include genetic counseling. PMID:12254320

Kumar, P

1968-11-01

85

Large P(T) jets observed in Chacaltaya gamma ray families  

Microsoft Academic Search

Large PT jets in high-energy gamma-ray families observed in Chacaltaya emulsion chambers at Sigma-E(gamma) = 100-1,000 TeV are studied. Through jet-cluster analysis it is found that families with large PT jets exist which cannot be from random jet production, but must be from interaction of exotic type with large PT.

H. Semba

1983-01-01

86

Familial gigantiform cementoma: classification and presentation of a large pedigree.  

PubMed

Very few cases of gigantiform cementoma have been reported, and those associated with a positive family history are especially rare. Confusion exists about the relationship of gigantiform cementoma to florid osseous dysplasia, cementifying fibroma, and diffuse chronic sclerosing osteomyelitis. It has been unclear whether gigantiform cementoma should be accorded the status of a separate entity. In this article, we report our findings on a family that, over five generations, has exhibited clinical, radiographic, and/or histologic findings consistent with the designation familial gigantiform cementoma. This pedigree consists of 55 members. Significant heterogeneity in expression of this trait was noted. The pattern of occurrence of the trait is consistent with an autosomal dominant mode of inheritance with variable expressivity of the phenotype. We suggest that familial gigantiform cementoma should be recognized as a separate entity. PMID:2594322

Young, S K; Markowitz, N R; Sullivan, S; Seale, T W; Hirschi, R

1989-12-01

87

Interplay of Socio-economic Factors, Consanguinity, Fertility, and Offspring Mortality in Monastir, Tunisia  

PubMed Central

Aim To assess the association among social status, prevalence of consanguineous marriages, and the effects of consanguinity on reproductive behavior and mortality in Tunisia. Methods The study included data on a total of 1741 live-births born from November 1989 to October 1990 in the maternity ward of the University-Hospital Fattouma Bourguiba of Monastir, Tunisia. After delivery, women filled out a questionnaire on the age of the parents at marriage, the number of pregnancies and abortions, the number of neonatal and post-neonatal deaths, and deaths of children under 5 years. Three categories of marriages were distinguished as follows: marriages between first cousins, marriages between cousins of other degree, and non consanguineous marriages. Results Consanguineous marriages represented 432 (24.81%) of the unions. Most consanguineous marriages were contracted between first cousins (n?=?303; 70.13%). Consanguineous couples had a lower age at marriage and a higher fertility index than non-consanguineous couples. The rates of spontaneous abortions and stillbirths were not correlated with consanguinity. However, higher rates of neonatal and post-neonatal deaths, and deaths of children younger than 5 years were observed in consanguineous couples. Conclusion Fertility index and mortality, especially in the first year of life, were significantly higher in consanguineous marriages. This important socio-economical factor needs to be considered in assessing equity on health in specific social and cultural contexts.

Kerkeni, Emna; Monastiri, Kamel; Seket, Besma; Guediche, Mohamed Neji; Ben Cheikh, Hassen

2007-01-01

88

Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population  

PubMed Central

Mucopolysaccharidosis type I (MPS I) was a group of rare autosomal recessive disorder caused by the deficiency of the lysosomal enzyme, alpha -L -iduronidase, and the resulting accumulation of undergraded dematan sulfate and heparan sulfate. MPS I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counseling and also impedes the selection and evaluation of patients undergoing therapy bone marrow transplantation. Aim of the study consanguinity rates have been determined among 14 families with mucopolysaccharidosis type I, seen in the pediatric departments of different geographic areas of Tunisia (Central and Southern areas) for the period August 2004 - August 2011 in order to investigate the relation between consanguinity and this disorder. Patients and methods Clinical and molecular analyses confirmed the diagnosis for MPS type I in the studied families. Results Most of the Tunisian MPS I patients have been identified at the homozygous status: p.P533R mutation (7 homozygous and one double heterozygous p.L578Q/p.P533R patients; 41.66% of all the investigated MPSI patients), p.F177S (1 homozygous patient; 5.55%), p.L530fs (1 patient; 5.55%), p.Y581X (2 patients; 11.11%), p.F602X (3 patients; 16.66%), p.R628X (1 patient; 5.55%). Another mutation: p.L578Q has been identified at the heterozygous status in the only double heterozygous p.L578Q/p.P533R case. Part of the mutations was the result of a founder effect. These described points are the consequences of the high rate of consanguinity. Conclusion The high frequency of p.P533R mutation could be explained by the high degree of inbreeding. This is due to the richness of the genetic background of the studied population. A multidisciplinary approach is essential to develop adequate preventive program adapted to the social, cultural, and economic context.

2011-01-01

89

Consanguinity and its effect on fetal growth and development: a south Indian study  

Microsoft Academic Search

The effect of consanguinity on fetal growth and development was studied in 3700 consecutive births (live and stillborn); 26% of the total births were to consanguineous couples. Hindus had a higher frequency of consanguineous marriages, uncle-niece unions being the commonest type, whereas Moslems preferred first cousin marriages. The incidence of congenital malformations was 39.1\\/1000 births with a significantly higher incidence

M L Kulkarni; M Kurian

1990-01-01

90

Asararenes--a family of large aromatic macrocycles.  

PubMed

We announce the establishment of a new family of macrocycles--the asararenes, which are based on para-methylene linked "asarol methyl ether" (1,2,4,5-tetramethoxybenzene) units. Macrocycles with 6-12 aromatic units have been synthesized and isolated in a single step from asarol methyl ether and paraformaldehyde. Even larger rings, with up to 15 asarol methyl ether units, have been observed by high-resolution mass spectrometry. Single-crystal X-ray structures of asar[6]-, asar[7]-, asar[8]-, asar[9]-, asar[10]- and asar[11]arene highlight the diverse structural features of this family of macrocycles. While the cavities of the asar[6-8]arene macrocycles are mostly filled with methoxyl groups, the asar[9]- and asar[10]arene rings contain accessible cavities and self-assemble into infinite channels filled with solvent molecules in the solid state. These solid-state structures highlight the potential of this family of macrocycles for a wide range of potential applications. PMID:23417890

Schneebeli, Severin T; Cheng, Chuyang; Hartlieb, Karel J; Strutt, Nathan L; Sarjeant, Amy A; Stern, Charlotte L; Stoddart, J Fraser

2013-02-18

91

Diagnosis of Bardet-Biedl Syndrome in Consecutive Pregnancies Affected with Echogenic Kidneys and Polydactyly in a Consanguineous Couple  

PubMed Central

Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathic human genetic disorder with variable expression that is difficult to diagnose in pregnancy without known risk factors. Homozygosity testing has been shown to be a useful tool in identifying BBS mutations and candidate genes in affected individuals. We present the first case of prenatal diagnosis of BBS in consecutive pregnancies aided by homozygosity testing via SNP microarray analysis. This case demonstrates a novel approach to the evaluation of recurrent echogenic kidneys in consanguineous couple with no significant family history.

Baker, Tieneka M.; Sturm, Erica L.; Turner, Clesson E.; Petersen, Scott M.

2013-01-01

92

Broad scan linkage analysis in a large Tourette family pedigree  

SciTech Connect

Attempts to find a gene causing Tourette syndrome (TS) using linkage analysis have been unsuccessful even though as much as 65% of the autosomal genetic map has been excluded by the pooled results from several laboratories collaborating worldwide. One reason for this failure may be the misclassification of affection status of marry-in spouses. Specifically, we have found that six unrelated spouses in our Utah TS pedigree suffer from TS, obsessive-compulsive disorder or chronic motor tics. In light of these findings we decided to conduct a complete genomic scan from this Utah kindred with polymorphic markers in three related sibships in which there was no assortative mating. A linkage study assuming autosomal dominant inheritance was done using tetranucleotide repeat markers developed at the University of Utah. We selected markers that were less than 300 bp in size and that gave a heterozygosity of over 70% upon analysis in 4 CEPH families. Results to date with 95 markers run at an interval of 30 cM (covering 61% of the genome) show no evidence of linkage. We intend to extend the coverage to 100% of the genome. Pending completion of this scan, failure to provide evidence of linkage in our TS pedigree might then be attributed to phenotypic misclassification or erroneous assumptions regarding the genetic model of transmission.

Peiffer, A.; Leppert, M. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States); Wetering, B.J.M. van der [Univ. Hospital Rotterdam (Netherlands)

1994-09-01

93

The effect of reproductive compensation on recessive disorders within consanguineous human populations  

Microsoft Academic Search

We investigate the effects of consanguinity and population substructure on genetic health using the UK Asian population as an example. We review and expand upon previous treatments dealing with the deleterious effects of consanguinity on recessive disorders and consider how other factors, such as population substructure, may be of equal importance. For illustration, we quantify the relative risks of recessive

A D J Overall; M Ahmad; R A Nichols

2002-01-01

94

Autosomal Dominant Retinitis Pigmentosa in a Large Family: A Clinical and Molecular Genetic Study  

Microsoft Academic Search

Purpose. To characterize the pedigree, visual function phenotype, and responsible mutation in a large family with autosomal dominant retinitis pigmentosa. Methods. Pedigree data were obtained by personal interviews and corroborated with commu- nity records. One hundred twenty-eight members of the family were examined clinically, and a subset of 12 affected subjects was further studied with dark- and light-adapted static perimetry

Delia J. Rosas; Jennifer P. Macke; Jeremy Nathans

1994-01-01

95

Linkage study of a large family with autosomal dominant polycystic kidney disease with reduced expression  

Microsoft Academic Search

We describe a large three generation family with autosomal dominant polycystic kidney disease (PKD). Ultrasonographic screening of 60 family members revealed 20 individuals, whose age ranged from ten to eighty years, with one or several cysts in only one kidney and 7 individuals with cysts in both kidneys. Transmission of unilateral cysts seems to be autosomal dominant, although there are

Lucien Bachner; Marie Claude Vinet; Roger Lacave; Marie Claude Babron; Eric Rondeau; Jean Daniel Sraer; Dominique Chevet; Jean-Claude Kaplan

1990-01-01

96

Access to Higher Education: Empirical Analysis of Data on Large Families  

Microsoft Academic Search

The paper contributes to Russian empirical literature on determinants of higher education using data from a small regional survey of large families. The binary probit estimation results are consistent with the traditional set of hypotheses. The educational choice of a child is affected by family characteristics, in the first place by the educational attainment of parents, as well as by

Maria Gorban

2010-01-01

97

Fertility Related Attitudes of Minority Mothers with Large and Small Families.  

ERIC Educational Resources Information Center

|The relationship between certain attitudes and the levels of fertility in five cultural groups was explored in this study. The group studied were blacks, Cubans, American Indians, migrant Chicanos, and white Protestants. Mothers, aged 35-45, with one or two children (small family) or five children (large family) were compared. Attitudes measured…

Linn, Margaret W.; And Others

98

Genetic screening in a large family with juvenile onset primary open angle glaucoma  

Microsoft Academic Search

AIMSA number of genetic loci have been implicated in the pathogenesis of primary open angle glaucoma (POAG). The aim of this study was to identify the genetic cause of POAG in a large Scottish family and, if possible, offer genetic screening and advice to family members.METHODSFamily members were examined to determine their disease status. Base excision sequence scanning was carried

Adam P Booth; Rashida Anwar; Hua Chen; Amanda J Churchill; Jeffrey Jay; Jon Polansky; Alexander F Markham

2000-01-01

99

Functional and structural analysis of members of the TorD family, a large chaperone family dedicated to molybdoproteins.  

PubMed

The trimethylamine N-oxide (TMAO) reductase TorA, a DMSO reductase family member, is a periplasmic molybdoenzyme of Escherichia coli. The cytoplasmic protein TorD acts as a chaperone for TorA, allowing the efficient insertion of the molybdenum cofactor into the apoform of the enzyme prior to its secretion. This paper demonstrates that TorD is a member of a large family of prokaryotic proteins that are structurally related. Moreover, their genes generally belong to operons also encoding molybdoenzymes of the DMSO reductase family. Both the TorD and the DMSO reductase families present a similar phylogenetic organization, suggesting a co-evolution of these two families of proteins. This hypothesis is also supported by the fact that the TorD and DmsD chaperones cannot replace each other and thus appear dedicated to specific molybdopartners. Interestingly, it was found that the positive effect of TorD on TorA maturation, and the partial inhibitory effect of DmsD and homologues, are independent of the TorA signal sequence. PMID:15073303

Ilbert, Marianne; Méjean, Vincent; Iobbi-Nivol, Chantal

2004-04-01

100

The first case of CDK5RAP2-related primary microcephaly in a non-consanguineous patient identified by next generation sequencing.  

PubMed

Primary autosomal recessive microcephaly (MCPH) is a genetically heterogeneous condition characterized by congenital microcephaly and intellectual disability. To date, 10 MCPH loci have been identified and due to the genetic heterogeneity of this condition, molecular testing for MCPH can be complicated. Our methods involved employing a next generation sequencing panel of MCPH-related genes allowing for the evaluation of multiple disease loci simultaneously. Next generation sequencing analysis of a 6year old female with primary microcephaly identified novel compound heterozygous mutations (c.524_528del and c.4005-1G>A) in the CDK5RAP2 gene. A review of the published literature to date reveals that only three mutations have been previously reported in the CDK5RAP2 gene in the homozygous state in three Northern Pakistani and one Somali consanguineous MCPH families. Our patient represents the first non-consanguineous Caucasian individual to have been identified with CDK5RAP2-related MCPH. As only a handful of patients have been reported in the literature with CDK5RAP2-related MCPH, we anticipate the identification of individuals with CDK5RAP2 mutations from all ethnic backgrounds will continue. Our patient contributes to the ethnic and genotypic spectrum of CDK5RAP2-related MCPH and supports the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations. Our results also highlight the utility of multi-gene sequencing panels to elucidate the etiology of genetically heterogeneous conditions. PMID:23726037

Tan, Christopher A; Topper, Scott; Ward Melver, Catherine; Stein, Jennifer; Reeder, Amanda; Arndt, Kelly; Das, Soma

2013-05-28

101

Autosomal dominant transmission of gouty arthritis with renal disease in a large Japanese family.  

PubMed Central

Six generations of a Japanese family had gouty arthritis and progressive nephropathy. Data on nine of 51 women (18%) and 15 of 66 men (23%) with either asymptomatic hyperuricaemia, gouty arthritis, or renal insufficiency were obtained. Renal function in four men and one woman with hyperuricaemia or gouty arthritis was also examined. Urinary excretion of uric acid was decreased in all subjects examined, including the young. Erythrocyte phosphoribosylpyrophosphate synthetase and hypoxanthine-guanine phosphoribosyltransferase activities determined in 10 patients were normal. Some patients had been treated with allopurinol to reduce serum uric acid concentrations, but the treatment did not prevent progression of renal impairment. Transmission of the disease in this large family is considered to be autosomal dominant. The data suggest that the disease in this family is the same entity as that described by other workers--that is, familial urate nephropathy. As far as is known this is the largest family with this disease so far reported.

Yokota, N; Yamanaka, H; Yamamoto, Y; Fujimoto, S; Eto, T; Tanaka, K

1991-01-01

102

Are family ownership and control in large firms good, bad, or irrelevant?  

Microsoft Academic Search

Family ownership and control play an important role in large firms in Asia. There is a puzzle regarding the relationship between\\u000a concentrated family ownership and control on the one hand and firm performance on the other hand. Three positions suggest\\u000a that such concentration may be good, bad, or irrelevant for firm performance. This article reports two studies to shed further

Yi Jiang; Mike W. Peng

2011-01-01

103

Phenocopies in a large GCH1 mutation positive family with dopa responsive dystonia: confusing the picture?  

PubMed Central

Objective: To study a large Canadian family with presumed DRD. Methods: The clinical features of the family were collected before molecular genetic mutational analysis. Results: All nine individuals in whom a clinical diagnosis of DRD was definite or probable were heterozygous for a GCH1 gene deletion. However, eight of nine possibly clinically affected members did not carry the GCH1 mutation. Conclusions: Great care must be taken in diagnosing DRD even in families with the classic phenotype, because of potential phenocopies of the disease.

Grimes, D; Barclay, C; Duff, J; Furukawa, Y; Lang, A

2002-01-01

104

OrthoRBH: A streamlined pipeline for mining large gene family sequences in related species  

PubMed Central

Plant and animal genomes are replete with large gene families, making the task of ortholog identification difficult and labor intensive. OrthoRBH is an automated reciprocal blast pipeline tool enabling the rapid identification of specific gene families of interest in related species, streamlining the collection of homologs prior to downstream molecular evolutionary analysis. The efficacy of OrthoRBH is demonstrated with the identification of the 13-member PYR/PYL/RCAR gene family in Hordeum vulgare using Oryza sativa query sequences. OrthoRBH runs on the Linux command line and is freely available at SourceForge. Availability http://sourceforge.net/projects/ orthorbh/

Ziemann, Mark; Kamboj, Atul; Bhave, Mrinal

2013-01-01

105

A large gene family for putative variant antigens shared by human and rodent malaria parasites.  

PubMed Central

A major mechanism whereby malaria parasites evade the host immune response to give chronic infections in patients' blood for months, or even years, is antigenic variation. In order to generate variant antigens, parasites require large multigene families. Although several gene families involved in these phenomena have been identified in the human malaria Plasmodium falciparum, to date no variant antigen gene families have been identified in malaria species that will infect widely used rodent laboratory hosts. Here we present, for the first time, to our knowledge, a large multigene family conserved in both rodent and human malarias, which is a strong candidate as a major variant antigen gene family. In each of four species of Plasmodium, three rodent malarias and the human pathogen P. vivax, homologues of the gene family were found to have a conserved three-exon structure. In the rodent malaria P. chabaudi, transcription of members of the gene family was developmentally regulated with maximum expression in late trophozoite stages, which is the developmental stage known to express variant antigen proteins.

Janssen, Christoph S; Barrett, Michael P; Turner, C Michael R; Phillips, R Stephen

2002-01-01

106

Biomarkers Associated with Clinical Phenotypes of Hand Osteoarthritis in a Large Multigenerational Family: the CARRIAGE Family Study  

PubMed Central

Objective To evaluate biological markers as potential quantitative traits of clinical osteoarthritis (OA) in a large multigenerational family in the Carolinas of the U.S. known as the CARRIAGE family. Methods During a series of three family reunions over 6 years, we ascertained 365 family members. We performed clinical hand examinations (n=287), and obtained sera (n=278) for seven OA-related biomarkers (PIIANP, CPII, C2C, COMP, HA, hs-CRP and glycated serum protein). Three hand OA definitions were evaluated - clinical ACR and GOGO criteria, and any single hand joint involvement. Non-hand OA was defined as a negative hand examination for OA but varying prevalence of joint symptoms; the control group was defined as having neither symptoms nor evidence for clinical hand OA. Results Mean ln HA, ln COMP, and ln hs-CRP were significantly higher in the hand OA group, compared with the non-hand OA or control group. Adjusted for age and sex, mean ln PIIANP (a collagen II synthesis marker) was significantly lower in the hand OA group compared with the other groups. Among those without clinical hand OA, Glycated serum protein was associated with hand joint symptoms. Conclusions This is the first report, to our knowledge, showing an association of OA biomarkers and hand OA based on physical examination alone. Analyses using these biomarkers as quantitative traits could reveal novel genetic loci and facilitate exploration of the genetic susceptibility to OA.

Chen, Hsiang-Cheng; Shah, Svati; Stabler, Thomas V; Li, Yi-Ju; Kraus, Virginia Byers

2012-01-01

107

The roles of segmental and tandem gene duplication in the evolution of large gene families in Arabidopsis thaliana  

Microsoft Academic Search

BACKGROUND: Most genes in Arabidopsis thaliana are members of gene families. How do the members of gene families arise, and how are gene family copy numbers maintained? Some gene families may evolve primarily through tandem duplication and high rates of birth and death in clusters, and others through infrequent polyploidy or large-scale segmental duplications and subsequent losses. RESULTS: Our approach

Steven B Cannon; Arvind Mitra; Andrew Baumgarten; Nevin D Young; Georgiana May

2004-01-01

108

Heritability of quantitative traits associated with type 2 diabetes mellitus in large multiplex families from South India  

Microsoft Academic Search

India is a major contributor to the global public health burden of diabetes. We have undertaken a family study of large multiplex families from Chennai, South India, and report on the familial aggregation of quantitative traits associated with type 2 diabetes mellitus in these pedigrees. Five hundred twenty-four individuals older than 19 years from 26 large multiplex pedigrees were ascertained.

Rasika A. Mathias; Mohan Deepa; Raj Deepa; Alexander F. Wilson; Vishwanathan Mohan

2009-01-01

109

The relationship between consanguineous marriage and death in fetus and infants  

PubMed Central

Background: Given the high prevalence of consanguineous marriages in rural and urban areas of Iran, the aim of this study was to identify its role in increasing fetal and infant deaths. Materials ans Methods: This was a cross-sectional study in which 494 mothers with more than one exceptional child (mentally retarded and physically-dynamically disabled) or with normal children were selected based on multi-stage random sampling method. Data was gathered using the features of parents with more than one exceptional child questionnaire. The validity and reliability of this questionnaire was acceptable. Hierarchical log-linear method was used for statistical analysis. Results: Consanguineous marriage significantly increased the number of births of exceptional children. Moreover, there was a significant relation between the history of fetal/infant death and belonging to the group. There was a significant relation between consanguineous marriage and the history of fetal/infant death which means consanguineous marriage increased the prevalence of fetal/infant death in parents with exceptional children rather than in parents with normal children. Conclusions: The rate of fetal/infant death in exceptional births of consanguineous marriages was higher than that of non-consanguineous marriages.

Mohammadi, Majid Mehr; Hooman, Heidar Ali; Afrooz, Gholam Ali; Daramadi, Parviz Sharifi

2012-01-01

110

Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: Doppler sonographic screening in a large family  

Microsoft Academic Search

Background\\/Aims: The prevalence of hepatic vascular malformations in hereditary hemorrhagic telangiectasia has been estimated in the literature on clinical criteria, thus giving unreliable data. In our study the presence of hepatic vascular malformations in hereditary hemorrhagic telangiectasia was evaluated in a large Italian family by using Doppler sonography as screening technique. Doppler sonographic findings were compared to computed tomography and

Elisabetta Buscarini; Luigi Buscarini; Cesare Danesino; Mauro Piantanida; Giuseppe Civardi; Pietro Quaretti; Sandro Rossi; Michele Di Stasi; Matteo Silva

1997-01-01

111

Genetic heterogeneity in psoriasis vulgaris based on linkage analyses of a large family material  

SciTech Connect

Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscore over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.

Wahlstroem, J.; Swanbeck, G.; Inerot, A. [ Univ. of Goeteborg (Sweden)] [and others

1994-09-01

112

Evaluating the feasibility of using candidate DNA barcodes in discriminating species of the large Asteraceae family  

PubMed Central

Background Five DNA regions, namely, rbcL, matK, ITS, ITS2, and psbA-trnH, have been recommended as primary DNA barcodes for plants. Studies evaluating these regions for species identification in the large plant taxon, which includes a large number of closely related species, have rarely been reported. Results The feasibility of using the five proposed DNA regions was tested for discriminating plant species within Asteraceae, the largest family of flowering plants. Among these markers, ITS2 was the most useful in terms of universality, sequence variation, and identification capability in the Asteraceae family. The species discriminating power of ITS2 was also explored in a large pool of 3,490 Asteraceae sequences that represent 2,315 species belonging to 494 different genera. The result shows that ITS2 correctly identified 76.4% and 97.4% of plant samples at the species and genus levels, respectively. In addition, ITS2 displayed a variable ability to discriminate related species within different genera. Conclusions ITS2 is the best DNA barcode for the Asteraceae family. This approach significantly broadens the application of DNA barcoding to resolve classification problems in the family Asteraceae at the genera and species levels.

2010-01-01

113

Challenges in the care for consanguineous couples: an exploratory interview study among general practitioners and midwives  

PubMed Central

Background It is often suggested that an effort must be made to increase awareness among consanguineous couples of their reproductive risk, and to refer them for genetic counseling if needed. Primary care professionals are considered most appropriate for addressing the subject and identifying couples at risk during consultations in their practice. This Dutch study aims to explore the experiences, attitudes and beliefs of such professionals regarding their care for consanguineous couples. Methods Sixteen semi-structured interviews were conducted with midwives and general practitioners. Results Although most primary care professionals considered it their task to inform couples about the risks of consanguinity, during consultations the topic was generally only briefly touched upon and quickly abandoned. Important reasons for this were professionals’ beliefs about religious and social values of couples, their low perception of the couples’ reproductive risk and expected limited feasibility of referral. Feelings of embarrassment regarding addressing consanguinity did not seem to play a significant role. Conclusions Primary care professional beliefs about their clients’ religious and social values, their attitudes toward the risk, and perceived limited options for referral seem to conflict with the professional norm to address the topic of consanguinity.

2012-01-01

114

Are consanguineous marriage and swaddling the risk factors of developmental dysplasia of the hip?  

PubMed

The purpose of this study was to investigate prospectively the effects of swaddling and consanguineous marriage on developmental dysplasia of the hip and associated risk factors. We screened by ultrasound 265 infants using the Graf method. The Pediatrics Department referred all newborn infants with suspected instability or a recognized risk factor to the orthopedic clinic. Risk factors of developmental dysplasia of the hip were searched and noted in these patients. Swaddling and consanguineous marriage were also determined and noted. We observed 164 of 265 infants (61.9 %) who had been swaddled and that 64 of 265 infants' parents were in a consanguineous marriage (24.2 %). In the statistical analysis that was conducted for swaddling and consanguineous marriage, highly significant differences were found. Our study showed that the rate of developmental dysplasia of the hip is very high, 11.7 %, in our region, eastern Turkey. Also, we commonly see improper swaddling and consanguineous marriage in our region, which affects many infants. PMID:23080296

Guner, Sukriye Ilkay; Guner, Savas; Peker, Erdal; Ceylan, Mehmet Fethi; Guler, Ayse; Turktas, Ugur; Kaki, Bar?s

2012-10-19

115

Trends in the frequencies of consanguineous marriages in the Israeli Arab community.  

PubMed

To assess the trends in the frequency of consanguineous marriages in the Israeli Arab population in the last 40 years, we conducted a two-part study. For the first part, we re-analyzed data from a nationwide study carried out in 1992, and for the second part, we undertook a new survey in 1998 in four locations: Taibe, Tira, Kalansuwa and Kafr Bara. Data regarding the frequency of consanguineous marriage in these four locations for the years 1961-1985 was extracted from the original survey, and for the years 1986-1998, from new questionnaires. The frequency of consanguineous marriage was highest in the period 1961 1965 (50.6%), but by the period 1981-1985 it had decreased to 40.6%. Over the whole time span of the 1992 study, a significant decrease was observed between the periods 1961-1975 and 1976-1985 (p < 0.0001). In the four-location study, there was a significant decrease in the frequency of consanguineous marriage from 52.9%, in the period 1961-1970 to 32.8% in the period 1991-1998 (p = 0.0006). We conclude that the custom of consanguineous marriage in the studied population is still extremely high, and preventive measures should be taken to decrease its frequency and associated complications. PMID:11005142

Jaber, L; Halpern, G J; Shohat, T

2000-08-01

116

Religious Support, Motives for Having Large Families, and Psychological Functioning Among Religious Jewish Mothers  

Microsoft Academic Search

The effects of religious support, maternal motivations for having large families, and their interactions on psychological\\u000a functioning were assessed in a sample of 79 religious Israeli Jewish mothers of six or more children. Religious support from\\u000a religious leaders, community, and G-d—as well as faith-focused maternal motivation—were all positively related to adaptive\\u000a psychological functioning. In contrast, self-focused maternal motivation was negatively

Jeffery P. Bjorck; Aryeh Lazar

2011-01-01

117

PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning  

Microsoft Academic Search

Noonan syndrome (NS, MIM 163950) is an autosomal dominant condition characterised by facial dysmorphy, congenital cardiac defects and short stature. Recently missense mutations in PTPN11, the gene encoding the nonreceptor protein tyrosine phosphatase SHP-2 on 12q24, were identified in 50% of analysed Noonan cases. A large four-generation Belgian family with NS and some features suggestive of cardio-facio-cutaneous syndrome (CFC) was

Els Schollen; Gert Matthijs; Marc Gewillig; Jean-Pierre Fryns; Eric Legius

2003-01-01

118

V804M RET mutation and familial medullary thyroid carcinoma: Report of a large family with expression of the disease only in the homozygous gene carriers  

Microsoft Academic Search

Background. Only 9 families with familial medullary thyroid carcinoma due to V804M mutation have been reported until now. We describe a large kindred with not only heterozygous but also homozygous members with the V804M mutation. This is, to our knowledge, the first report of a homozygous RET mutation. Methods. Fifty-three members from 4 successive generations of a family with a

Albert Lecube; Cristina Hernandez; Josep Oriola; Rosa Galard; Enrique Gémar; Jorge Mesa; Rafael Simó

2002-01-01

119

Genome-scale phylogenetic function annotation of large and diverse protein families.  

PubMed

The Statistical Inference of Function Through Evolutionary Relationships (SIFTER) framework uses a statistical graphical model that applies phylogenetic principles to automate precise protein function prediction. Here we present a revised approach (SIFTER version 2.0) that enables annotations on a genomic scale. SIFTER 2.0 produces equivalently precise predictions compared to the earlier version on a carefully studied family and on a collection of 100 protein families. We have added an approximation method to SIFTER 2.0 and show a 500-fold improvement in speed with minimal impact on prediction results in the functionally diverse sulfotransferase protein family. On the Nudix protein family, previously inaccessible to the SIFTER framework because of the 66 possible molecular functions, SIFTER achieved 47.4% accuracy on experimental data (where BLAST achieved 34.0%). Finally, we used SIFTER to annotate all of the Schizosaccharomyces pombe proteins with experimental functional characterizations, based on annotations from proteins in 46 fungal genomes. SIFTER precisely predicted molecular function for 45.5% of the characterized proteins in this genome, as compared with four current function prediction methods that precisely predicted function for 62.6%, 30.6%, 6.0%, and 5.7% of these proteins. We use both precision-recall curves and ROC analyses to compare these genome-scale predictions across the different methods and to assess performance on different types of applications. SIFTER 2.0 is capable of predicting protein molecular function for large and functionally diverse protein families using an approximate statistical model, enabling phylogenetics-based protein function prediction for genome-wide analyses. The code for SIFTER and protein family data are available at http://sifter.berkeley.edu. PMID:21784873

Engelhardt, Barbara E; Jordan, Michael I; Srouji, John R; Brenner, Steven E

2011-07-22

120

Genome-scale phylogenetic function annotation of large and diverse protein families  

PubMed Central

The Statistical Inference of Function Through Evolutionary Relationships (SIFTER) framework uses a statistical graphical model that applies phylogenetic principles to automate precise protein function prediction. Here we present a revised approach (SIFTER version 2.0) that enables annotations on a genomic scale. SIFTER 2.0 produces equivalently precise predictions compared to the earlier version on a carefully studied family and on a collection of 100 protein families. We have added an approximation method to SIFTER 2.0 and show a 500-fold improvement in speed with minimal impact on prediction results in the functionally diverse sulfotransferase protein family. On the Nudix protein family, previously inaccessible to the SIFTER framework because of the 66 possible molecular functions, SIFTER achieved 47.4% accuracy on experimental data (where BLAST achieved 34.0%). Finally, we used SIFTER to annotate all of the Schizosaccharomyces pombe proteins with experimental functional characterizations, based on annotations from proteins in 46 fungal genomes. SIFTER precisely predicted molecular function for 45.5% of the characterized proteins in this genome, as compared with four current function prediction methods that precisely predicted function for 62.6%, 30.6%, 6.0%, and 5.7% of these proteins. We use both precision-recall curves and ROC analyses to compare these genome-scale predictions across the different methods and to assess performance on different types of applications. SIFTER 2.0 is capable of predicting protein molecular function for large and functionally diverse protein families using an approximate statistical model, enabling phylogenetics-based protein function prediction for genome-wide analyses. The code for SIFTER and protein family data are available at http://sifter.berkeley.edu.

Engelhardt, Barbara E.; Jordan, Michael I.; Srouji, John R.; Brenner, Steven E.

2011-01-01

121

Genomewide Linkage Scan for Split-Hand/Foot Malformation with Long-Bone Deficiency in a Large Arab Family Identifies Two Novel Susceptibility Loci on Chromosomes 1q42.2-q43 and 6q14.1  

PubMed Central

Split–hand/foot malformation with long-bone deficiency (SHFLD) is a rare, severe limb deformity characterized by tibia aplasia with or without split-hand/split-foot deformity. Identification of genetic susceptibility loci for SHFLD has been unsuccessful because of its rare incidence, variable phenotypic expression and associated anomalies, and uncertain inheritance pattern. SHFLD is usually inherited as an autosomal dominant trait with reduced penetrance, although recessive inheritance has also been postulated. We conducted a genomewide linkage analysis, using a 10K SNP array in a large consanguineous family (UR078) from the United Arab Emirates (UAE) who had disease transmission consistent with an autosomal dominant inheritance pattern. The study identified two novel SHFLD susceptibility loci at 1q42.2-q43 (nonparametric linkage [NPL] 9.8, P=.000065) and 6q14.1 (NPL 7.12, P=.000897). These results were also supported by multipoint parametric linkage analysis. Maximum multipoint LOD scores of 3.20 and 3.78 were detected for genomic locations 1q42.2-43 and 6q14.1, respectively, with the use of an autosomal dominant mode of inheritance with reduced penetrance. Haplotype analysis with informative crossovers enabled mapping of the SHFLD loci to a region of ?18.38 cM (8.4 Mb) between single-nucleotide polymorphisms rs1124110 and rs535043 on 1q42.2-q43 and to a region of ?1.96 cM (4.1 Mb) between rs623155 and rs1547251 on 6q14.1. The study identified two novel loci for the SHFLD phenotype in this UAE family.

Naveed, Mohammed; Nath, Swapan K.; Gaines, Mathew; Al-Ali, Mahmoud T.; Al-Khaja, Najib; Hutchings, David; Golla, Jeffrey; Deutsch, Samuel; Bottani, Armand; Antonarakis, Stylianos E.; Ratnamala, Uppala; Radhakrishna, Uppala

2007-01-01

122

Parental Consanguinity and the Risk of Primary Immunodeficiency Disorders: Report from the Kuwait National Primary Immunodeficiency Disorders Registry  

Microsoft Academic Search

Background: It is proposed that consanguineous marriages increase the risk of primary immunodeficiency disorders (PID). The aim of this study is to review the frequency and pattern of parental consanguinity among PID patients and to determine its effects on the distribution of different PID, the patients’ performance status and the risk of death. Method: The data was obtained from the

Waleed Al-Herz; Kamal K. Naguib; Luigi D. Notarangelo; Raif S. Geha; Amal Alwadaani

2011-01-01

123

UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family  

PubMed Central

Background The primary objective of this study is to identify novel copy number variations (CNVs) associated with familial ankylosing spondylitis (AS). A customized genome-wide microarray was designed to detect CNVs and applied to a multiplex AS family with six (6) affected family members. CNVs were detected using the built-in DNA analytics aberration detection method-2 (ADM-2) algorithm. Gene enrichment analysis was performed to observe the segregation. Subsequent validation was performed using real time quantitative fluorescence polymerase reaction (QF-PCR). The frequency of copy number variation for the UGT2B17 gene was then performed on two well-defined AS cohorts. Fisher exact test was performed to quantify the association. Results Our family-based analysis revealed ten gene-enriched CNVs that segregate with all six family members affected with AS. Based on the proposed function and the polymorphic nature of the UGT2B17 gene, the UGT2B17 gene CNV was selected for validation using real time QF-PCR with full concordance. The frequency of two copies of the UGT2B17 gene CNV was 0.41 in the Newfoundland AS cases and 0.35 in the Newfoundland controls (OR = 1.26(0.99-1.59); p < 0.05)), whereas the frequency of two (2) copies of the UGT2B17 gene CNV was 0.40 in the Alberta AS cases and 0.39 in the Alberta controls (OR = 1.05(95% CI: 0.83-1.33); p < 0.71)). Conclusions A genome-wide microarray interrogation of a large multiplex AS family revealed segregation of the UGT2B17 gene CNV among all affected family members. The association of the UGT2B17 CNV with AS is particularly interesting given the recent association of this CNV with osteoporosis and the proposed function as it encodes a key enzyme that inhibits androgens. However, two copies of the UGT2B17 gene CNV were only marginally significant in a uniplex AS cohort from Newfoundland but not in a uniplex AS cohort from Alberta.

2013-01-01

124

Consanguinity: A Risk Factor for Preterm Birth at Less Than 33 Weeks' Gestation  

PubMed Central

Consanguinity promotes homozygosity of recessive susceptibility gene variants and can be used to investigate a recessive component in diseases whose inheritance is uncertain. The objective of this study was to assess the association between consanguinity and preterm birth (PTB), stratified by gestational age and clinical presentation (spontaneous vs. medically indicated). Data were collected on 39,745 singleton livebirths without major birth defects, admitted to 19 hospitals in Lebanon, from September 2003 to December 2007. Deliveries before completed 33 weeks’ gestation and deliveries at 33–36 weeks’ gestation were compared, with respect to cousin marriage, with those after completed 36 weeks’ gestation by using multinomial multiple logistic regression. Overall, infants of consanguineous parents had a statistically significant 1.6-fold net increased risk of being born at less than 33 weeks’ gestation compared with infants of unrelated parents. This association was statistically significant only with spontaneous PTB. There was no increased risk of being born at 33–36 weeks’ gestation associated with consanguinity for both clinical presentations of PTB. Our findings support a genetic contribution to early onset PTB and suggest that early PTB should be targeted in future genetic studies rather than the classic lumping of all births less than 37 weeks’ gestation.

Mumtaz, Ghina; Nassar, Anwar H.; Mahfoud, Ziyad; El-Khamra, Akaber; Al-Choueiri, Nathalie; Adra, Abdallah; Murray, Jeffrey C.; Zalloua, Pierre; Yunis, Khalid A.

2010-01-01

125

The Effect of Consanguineous Marriage on Reading Disability in the Arab Community  

ERIC Educational Resources Information Center

|The present study examined the effect of consanguineous marriage in the Arab community on reading disabilities of offspring. It examined whether the rate of reading disabilities was higher among offspring of first-cousin parents than offspring of unrelated parents; and whether reading-disabled children of first-cousin parents were more disabled…

Abu-Rabia, Salim; Maroun, Lateefeh

2005-01-01

126

The Prevalence of Attention Deficit Hyperactivity Symptoms in Schoolchildren in a Highly Consanguineous Community  

Microsoft Academic Search

Objective: The objective of the present study was to find the prevalence of attention deficit hyperactivity (ADH) symptoms in a sample of primary schoolchildren in Qatar and investigate the behaviour of the children with and without ADH symptoms in a highly consanguineous community. Subjects and Methods: A total of 2,500 primary school students, aged 6–12 years, were randomly selected from

Abdulbari Bener; Razna Al Qahtani; Ahmad S. Teebi; Mohammed Bessisso

2008-01-01

127

Clinic and genetic evaluation of variegate porphyria (VP) in a large family from the Balearic Islands.  

PubMed

Variegate porphyria (VP) (an autosomal dominant disease), is clinically characterized by skin photosensitivity and/or acute neurovisceral crises and biochemically by high levels of faecal protoporphyrin and coproporphyrin. It results from the partial deficiency of protoporphyrinogen oxidase (PPOX gene). Genetic heterogeneity has been reported in this gene, although no genotype-phenotype correlation has been evidenced. We have sequenced 27 members of a single large Majorcan family with several individuals that exhibit VP symptoms: two of the eight patients had only skin symptoms (25%), one patient had only acute visceral crises (12.5%), one patient had both manifestations (12.5%) and the rest were completely asymptomatic (50%). In eight individuals, a T>A transversion at the intron 6 consensus splicing site was found (IVS6+2T>A), but only four of them presented clinical symptoms. We have also detected four polymorphic positions, three non-coding and one non-synonymous coding: c.-414A>C; IVS2+121G>C; c.1188G>A and IVS12+34C>T. Although IVS12+34C>T change has been reported to cause VP, generalized linear model (GLM) analyses showed no significant association between these SNPs and phenotypic manifestations. Only three mtDNA haplogroups were detected in this family: H, K and U(5a1). Two of them are relatively common in Balearic Islands. Our family evidenced a positive correlation between the clinically overt VP and haplogroup H. Thus, it seems that, in this family, the haplogroup H could be involved in the expression of the disease. The GLM analyses evidenced an association between haplogroup H, mutation IVS6+2T>A and clinically overt variegate porphyria. PMID:19229653

Bonnin, A; Picornell, A; Orfila, J; Castro, J A; Ramon, M M

2009-02-20

128

Signals of supersymmetry with inaccessible first two families at the Large Hadron Collider  

SciTech Connect

We investigate the signals of supersymmetry in a scenario where only the third family squarks and sleptons can be produced at the Large Hadron Collider, in addition to the gluino, charginos, and neutralinos. The final states in such cases are marked by a multiplicity of top or bottom quarks. We study, in particular, the case when the top squark, bottom squark, and gluino masses are near the TeV scale due to which, the final state t's and b's are very energetic. We point out the difficulty in b tagging and identifying energetic tops and suggest several event selection criteria which allow the signals to remain significantly above the standard model background. We show that such scenarios with gluino mass up to 2 TeV can be successfully probed at the Large Hadron Collider. Information on tan{beta} can also be obtained by looking at associated Higgs production in the cascades of accompanying neutralinos. We also show that a combined analysis of event rates in the different channels and the effective mass distribution allows one to differentiate this scenario from the one where all three sfermion families are accessible.

Desai, Nishita; Mukhopadhyaya, Biswarup [Regional Centre for Accelerator-based Particle Physics, Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad-211 019 (India)

2009-09-01

129

Annotation and analysis of a large cuticular protein family with the R&R Consensus in Anopheles gambiae  

Microsoft Academic Search

BACKGROUND: The most abundant family of insect cuticular proteins, the CPR family, is recognized by the R&R Consensus, a domain of about 64 amino acids that binds to chitin and is present throughout arthropods. Several species have now been shown to have more than 100 CPR genes, inviting speculation as to the functional importance of this large number and diversity.

R Scott Cornman; Toru Togawa; W Augustine Dunn; Ningjia He; Aaron C Emmons; Judith H Willis

2008-01-01

130

A large and functionally diverse family of Fad2 genes in safflower (Carthamus tinctorius L.)  

PubMed Central

Background The application and nutritional value of vegetable oil is highly dependent on its fatty acid composition, especially the relative proportion of its two major fatty acids, i.e oleic acid and linoleic acid. Microsomal oleoyl phosphatidylcholine desaturase encoded by FAD2 gene is known to introduce a double bond at the ?12 position of an oleic acid on phosphatidylcholine and convert it to linoleic acid. The known plant FAD2 enzymes are encoded by small gene families consisting of 1-4 members. In addition to the classic oleate ?12-desaturation activity, functional variants of FAD2 that are capable of undertaking additional or alternative acyl modifications have also been reported in a limited number of plant species. In this study, our objective was to identify FAD2 genes from safflower and analyse their differential expression profile and potentially diversified functionality. Results We report here the characterization and functional expression of an exceptionally large FAD2 gene family from safflower, and the temporal and spatial expression profiles of these genes as revealed through Real-Time quantitative PCR. The diversified functionalities of some of the safflower FAD2 gene family members were demonstrated by ectopic expression in yeast and transient expression in Nicotiana benthamiana leaves. CtFAD2-1 and CtFAD2-10 were demonstrated to be oleate desaturases specifically expressed in developing seeds and flower head, respectively, while CtFAD2-2 appears to have relatively low oleate desaturation activity throughout the plant. CtFAD2-5 and CtFAD2-8 are specifically expressed in root tissues, while CtFAD2-3, 4, 6, 7 are mostly expressed in the cotyledons and hypocotyls in young safflower seedlings. CtFAD2-9 was found to encode a novel desaturase operating on C16:1 substrate. CtFAD2-11 is a tri-functional enzyme able to introduce a carbon double bond in either cis or trans configuration, or a carbon triple (acetylenic) bond at the ?12 position. Conclusions In this study, we isolated an unusually large FAD2 gene family with 11 members from safflower. The seed expressed FAD2 oleate ?12 desaturase genes identified in this study will provide candidate targets to manipulate the oleic acid level in safflower seed oil. Further, the divergent FAD2 enzymes with novel functionality could be used to produce rare fatty acids, such as crepenynic acid, in genetically engineered crop plants that are precursors for economically important phytoalexins and oleochemical products.

2013-01-01

131

Members of a large retroposon family are determinants of post-transcriptional gene expression in Leishmania.  

PubMed

Trypanosomatids are unicellular protists that include the human pathogens Leishmania spp. (leishmaniasis), Trypanosoma brucei (sleeping sickness), and Trypanosoma cruzi (Chagas disease). Analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. Using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the Leishmania major genome two new large families of small elements--LmSIDER1 (785 copies) and LmSIDER2 (1,073 copies)--that fulfill all the characteristics of extinct trypanosomatid retroposons. LmSIDERs are approximately 70 times more abundant in L. major compared to T. brucei and are found almost exclusively within the 3'-untranslated regions (3'UTRs) of L. major mRNAs. We provide experimental evidence that LmSIDER2 act as mRNA instability elements and that LmSIDER2-containing mRNAs are generally expressed at lower levels compared to the non-LmSIDER2 mRNAs. The considerable expansion of LmSIDERs within 3'UTRs in an organism lacking transcriptional control and their role in regulating mRNA stability indicate that Leishmania have probably recycled these short retroposons to globally modulate the expression of a number of genes. To our knowledge, this is the first example in eukaryotes of the domestication and expansion of a family of mobile elements that have evolved to fulfill a critical cellular function. PMID:17907803

Bringaud, Frédéric; Müller, Michaela; Cerqueira, Gustavo Coutinho; Smith, Martin; Rochette, Annie; El-Sayed, Najib M A; Papadopoulou, Barbara; Ghedin, Elodie

2007-09-01

132

Hypertrophic cardiomyopathy in three generations of a large Norwegian family. A clinical, echocardiographic, and genetic study.  

PubMed Central

Hypertrophic cardiomyopathy is a heart muscle disease with an obscure aetiology. Data from four generations of a large family (71 members) are presented. The occurrence of hypertrophic cardiomyopathy among members of the two oldest generations was compatible with a pattern of autosomal dominant inheritance. Seven out of 14 siblings in the second generation had definite signs of or were clinically suspected of having hypertrophic cardiomyopathy. The severity and distribution of left ventricular hypertrophy varied, but three (21%) brothers in generation II showed the classic picture of left ventricular outflow obstruction. Four siblings (29%) died suddenly aged 11, 22, 38, and 40 years. A high incidence of the disease would have been expected in the two younger generations (41 members, aged 1-31 years), but only two, a 16 year old boy and a 17 year old girl had signs of asymmetric septal hypertrophy. Current diagnostic procedures, including M mode and cross sectional echocardiography, are not sufficiently sensitive to identify young family members who may have preclinical hypertrophic cardiomyopathy. No evidence for close genetic linkage between a postulated locus for hypertrophic cardiomyopathy and the major histocompatibility complex (antigens HLA-A, HLA-B, and HLA-DR) was found. Images Fig. 2 Fig. 3

Haugland, H; Ohm, O J; Boman, H; Thorsby, E

1986-01-01

133

Evidence for oligogenic inheritance of type 1 diabetes in a large Bedouin Arab family.  

PubMed Central

Based on a genomic search for linkage, a locus contributing to type 1 diabetes in a large Bedouin Arab family (19 affected relatives) maps to the long arm of chromosome 10 (10q25; nonparametric linkage = 4.99; P = 0.00004). All affected relatives carry one or two high-risk HLA-DR3 haplotypes that are rarely found in other family members. One chromosome 10 haplotype, the B haplotype, was transmitted from a heterozygous parent to 13 of 13 affected offspring compared to 10 of 23 unaffected siblings. Recombination events occurring on this haplotype place the susceptibility locus in an 8-cM interval between markers D10S1750 and D10S1773. Two adjacent markers, D10S592 and D10S554, showed evidence of linkage disequilibrium with the disease locus. A 273-bp allele at D10S592 was transmitted to 8 of 10 affected offspring compared to 3 of 14 unaffected siblings, and a 151-bp allele at D10S554 was transmitted to 15 of 15 affected offspring compared with 10 of 24 unaffected siblings. D10S554 and D10S592 and the closest flanking markers are contained in a 1,240-kb yeast artificial chromosome, a region small enough to proceed with positional cloning.

Verge, C F; Vardi, P; Babu, S; Bao, F; Erlich, H A; Bugawan, T; Tiosano, D; Yu, L; Eisenbarth, G S; Fain, P R

1998-01-01

134

A preliminary report of Norplant implant insertions in a large urban family planning program.  

PubMed

During the 21-month period between August 1, 1991, and April 30, 1993, 2,358 women received Norplant system insertions in either Parkland Memorial Hospital or the Dallas Maternal Health and Family Planning clinics. Forty-three percent of these women were teenagers with 14% 16 years of age or less. Overall, 431 patients received Norplant implants insertions postpartum prior to discharge from the hospital. To date, 138 Norplant systems have been removed, with the proportion of contraceptive implant removals among teenagers being essentially the same as that in more mature women. Of the reasons given by women discontinuing the Norplant system, an unanticipated high incidence of pain in the arm containing the implants, hair loss, and mood changes were noted. We have found the Norplant system to be a highly effective and highly acceptable contraceptive method for a large number of indigent women. PMID:8222663

Crosby, U D; Schwarz, B E; Gluck, K L; Heartwell, S F

1993-10-01

135

Germline BHD-Mutation Spectrum and Phenotype Analysis of a Large Cohort of Families with Birt-Hogg-Dub? Syndrome  

PubMed Central

Birt-Hogg-Dubé syndrome (BHD), a genodermatosis characterized by multiple hamartomas of the hair follicle (fibrofolliculoma), predisposes individuals to an increased risk of developing renal neoplasms and spontaneous pneumothorax. Previously, we localized the BHD locus (also known as FLCN) to chromosome 17p11.2 by linkage analysis and subsequently identified germline mutations in a novel gene in probands from eight of the nine families with BHD in our screening panel. Affected members of five of the families inherited an insertion/deletion of a cytosine in a C8 tract in exon 11. This mutation was also identified by exon 11 screening in probands from 22 of 52 additional families with BHD and therefore represents a hypermutable “hotspot” for mutation in BHD. Here, we screened the remaining 30 families from this large BHD cohort by direct sequence analysis and identified germline BHD mutations in 84% (51/61) of all families with BHD recruited to our study. Mutations were located along the entire length of the coding region, including 16 insertion/deletion, 3 nonsense, and 3 splice-site mutations. The majority of BHD mutations were predicted to truncate the BHD protein, folliculin. Among patients with a mutation in the exon 11 hotspot, significantly fewer renal tumors were observed in patients with the C-deletion than those with the C-insertion mutation. Coding-sequence mutations were not found, however, in probands from two large families with BHD whose affected members shared their family’s BHD-affected haplotype. Of the 53 families with BHD whose members inherited either a germline mutation or the affected haplotype, 24 (45%) had at least one member with renal neoplasms. Three families classified with familial renal oncocytoma were identified with BHD mutations, which represents the first disease gene associated with this rare form of renal neoplasm. This study expands the BHD-mutation spectrum and evaluates genotype-phenotype correlations among families with BHD.

Schmidt, Laura S.; Nickerson, Michael L.; Warren, Michelle B.; Glenn, Gladys M.; Toro, Jorge R.; Merino, Maria J.; Turner, Maria L.; Choyke, Peter L.; Sharma, Nirmala; Peterson, James; Morrison, Patrick; Maher, Eamonn R.; Walther, McClellan M.; Zbar, Berton; Linehan, W. Marston

2005-01-01

136

Functional divergence of the glutathione S-transferase supergene family in Physcomitrella patens reveals complex patterns of large gene family evolution in land plants.  

PubMed

Plant glutathione S-transferases (GSTs) are multifunctional proteins encoded by a large gene family that play major roles in the detoxification of xenobiotics and oxidative stress metabolism. To date, studies on the GST gene family have focused mainly on vascular plants (particularly agricultural plants). In contrast, little information is available on the molecular characteristics of this large gene family in nonvascular plants. In addition, the evolutionary patterns of this family in land plants remain unclear. In this study, we identified 37 GST genes from the whole genome of the moss Physcomitrella patens, a nonvascular representative of early land plants. The 37 P. patens GSTs were divided into 10 classes, including two new classes (hemerythrin and iota). However, no tau GSTs were identified, which represent the largest class among vascular plants. P. patens GST gene family members showed extensive functional divergence in their gene structures, gene expression responses to abiotic stressors, enzymatic characteristics, and the subcellular locations of the encoded proteins. A joint phylogenetic analysis of GSTs from P. patens and other higher vascular plants showed that different class GSTs had distinct duplication patterns during the evolution of land plants. By examining multiple characteristics, this study revealed complex patterns of evolutionary divergence among the GST gene family in land plants. PMID:23188805

Liu, Yan-Jing; Han, Xue-Min; Ren, Lin-Ling; Yang, Hai-Ling; Zeng, Qing-Yin

2012-11-27

137

Whole genome analysis in a consanguineous family with early onset Alzheimer's disease  

Microsoft Academic Search

Early-onset Alzheimer's disease (EOAD) is a clinically and genetically heterogeneous condition in which the typical features appear significantly earlier in life (before 65 years). Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in autosomal dominant forms of EOAD. However, in about 50% of Mendelian cases and in most of the sporadic EOAD patients, no mutations have been

J. Clarimón; R. Djaldetti; A. Lleó; R. J. Guerreiro; J. L. Molinuevo; C. Paisán-Ruiz; T. Gómez-Isla; R. Blesa; A. Singleton; J. Hardy

2009-01-01

138

Several Families of Sequences with Low Correlation and Large Linear Span  

NASA Astrophysics Data System (ADS)

In DS-CDMA systems and DS-UWB radios, low correlation of spreading sequences can greatly help to minimize multiple access interference (MAI) and large linear span of spreading sequences can reduce their predictability. In this letter, new sequence sets with low correlation and large linear span are proposed. Based on the construction Trm1[Trnm(?bt+?i?dt)]r for generating p-ary sequences of period pn-1, where n=2m, d=upm±v, b=u±v, ?i?GF(pn), and p is an arbitrary prime number, several methods to choose the parameter d are provided. The obtained sequences with family size pn are of four-valued, five-valued, six-valued or seven-valued correlation and the maximum nontrivial correlation value is (u+v-1)pm-1. The simulation by a computer shows that the linear span of the new sequences is larger than that of the sequences with Niho-type and Welch-type decimations, and similar to that of [10].

Zeng, Fanxin; Zhang, Zhenyu

139

Family Strengthening Writ Large: On becoming a Nation that Promotes Strong Families and Successful Youth. Policy Brief No. 24  

ERIC Educational Resources Information Center

Culture and systemic change are paramount to achieving significant and long-lasting gains in child and youth wellbeing and, in time, securing the future of our nation. This brief, based on a high-level synthesis of eight years of experience and research in place-based family strengthening, makes the case for a national transformation to a society…

Online Submission, 2007

2007-01-01

140

A 5-year survey of biopsy proven kidney diseases in Lebanon: significant variation in prevalence of primary glomerular diseases by age, population structure and consanguinity  

PubMed Central

Background. Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years’ detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon. Methods. Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents’ consanguinity were recorded when feasible. Results. The mean age at renal biopsy was 36.76 ± 20 years (range 1–84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001). Conclusions. Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important implications for formulating renal health policies and designing research studies in this population.

Karnib, Hussein H.; Gharavi, Ali G.; Aftimos, Georges; Mahfoud, Ziyad; Saad, Reem; Gemayel, Elias; Masri, Badiaa; Assaad, Shafika; Badr, Kamal F.; Ziyadeh, Fuad N.

2010-01-01

141

A high prevalence of consanguineous and severe congenital hypothyroidism in an Iranian population.  

PubMed

To determine the incidence of permanent congenital hypothyroidism (CH) in Tehran and Damavand, cord blood spots were collected from February 1998-August 2002 and infants with TSH > or =20 mU/l were recalled. CH was confirmed in neonates (aged > or =7 days) with serum TSH >10 mU/l and T4 <84 nmol/l. Cases were followed up until September 2003. Dysgenesis was detected by thyroid imaging. In eutopic cases, serum TSH and T4 measurements following levothyroxine discontinuation (2-3 years of age) confirmed dyshormonogenesis and transient CH. Of 35,067 neonates, 373 (1.06%) were recalled and 25 (1:1,403 births) had permanent CH (six had transient CH and four remain unknown). Dysgenesis was detected in 18 (1:1,948 births) and dyshormonogenesis in seven (1:5,010 births) infants. Parental consanguinity was present in 10 (55.6%) dysgenetic, three (42.9%) dyshormonogenetic, and overall 6,648 (28.6%) of 23,227 screened infants. Odds ratio (95%CI(OR)) of consanguinity in permanent CH and dysgenesis was 2.75 (1.17-6.47) and 3.74 (1.33-10.52), respectively. The high prevalence of parental consanguinity in infants with permanent CH warrants genetic assessment. PMID:15506679

Ordookhani, Arash; Mirmiran, Parvin; Moharamzadeh, Masoud; Hedayati, Mehdi; Azizi, Fereidoun

2004-09-01

142

SDR and MDR: completed genome sequences show these protein families to be large, of old origin, and of complex nature  

Microsoft Academic Search

Short-chain dehydrogenases\\/reductases (SDR) and medium-chain dehydrogenases\\/reductases (MDR) are protein families originally distinguished from characterisations of alcohol dehydrogenase of these two types. Screening of completed genome sequences now reveals that both these families are large, wide-spread and complex. In Escherichia coli alone, there are no fewer than 17 MDR forms, identified as open reading frames, considerably extending previously known MDR relationships

Hans Jörnvall; Jan-Olov Höög; Bengt Persson

1999-01-01

143

Extraordinary diversity among members of the large gene family, 185\\/333, from the purple sea urchin, Strongylocentrotus purpuratus  

Microsoft Academic Search

BACKGROUND: Recent analysis of immune-related genes within the sea urchin genome revealed a number of large gene families with vertebrate homologues, such as the Toll-like and NOD\\/NALP-like receptor families and C-type lectins in addition to a rudimentary complement system. Therefore, the immune response of the purple sea urchin appears to be more complex than previously believed. Another component of the

Katherine M Buckley; L Courtney Smith

2007-01-01

144

Intense paramagnon excitations in a large family of high-temperature superconductors  

NASA Astrophysics Data System (ADS)

Motivated by the search for the mechanism of high-temperature superconductivity, an intense research effort has been focused on the evolution of the spin excitation spectrum upon doping from the antiferromagnetic insulating to the superconducting states of the cuprates. Because of technical limitations, however, the experimental investigation of doped cuprates has been largely focused on excitations with energies <=100 meV in a small range of momentum space [1]. Here we take advantage of the recent developments of high-resolution resonant inelastic x-ray scattering [2,3] to show that a large family of superconductors, encompassing the model compounds YBa2Cu4O8 and YBa2Cu3O7, exhibits damped spin excitations - or paramagnons - with dispersions and spectral weights closely similar to those of magnons in undoped, antiferromagnetically ordered cuprates over much of the Brillouin zone. The results are in excellent agreement with the spin excitations obtained by exact diagonalization of the t-J Hamiltonian on finite-sized clusters. A numerical solution of the Eliashberg equations based on the experimental spin excitation spectrum of YBa2Cu3O7 reproduces its superconducting transition temperature Tc within a factor of two. The discovery of a well-defined, surprisingly simple spin excitation branch over a wide range of doping levels thus strongly supports magnetic Cooper pairing models for the cuprates [4]. [4pt] [1] M. Fujita et al. arXiv/condmat:1108.4431[0pt] [2] G. Ghiringhelli et al., Review of Scientific Instruments, 77, (2006).[0pt] [3] L. Braicovich et al., Phys. Rev. Lett., 104, 077002 (2010).[0pt] [4] M. Le Tacon et al., Nature Physics 7, 725 (2011).

Le Tacon, Mathieu

2012-02-01

145

Application of a high-throughput genotyping method for loci exclusion in non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa  

PubMed Central

Purpose Retinitis pigmentosa (RP) is the most common form of inherited blindness, caused by progressive degeneration of photoreceptor cells in the retina, and affects approximately 1 in 3,000 people. Over the past decade, significant progress has been made in gene therapy for RP and related diseases, making genetic characterization increasingly important. Recently, high-throughput technologies have provided an option for reasonably fast, cost-effective genetic characterization of autosomal recessive RP (arRP). The current study used a single nucleotide polymorphism (SNP) genotyping method to exclude up to 28 possible disease-causing genes in 31 non-consanguineous Australian families affected by arRP. Methods DNA samples were collected from 59 individuals affected with arRP and 74 unaffected family members from 31 Australian families. Five to six SNPs were genotyped for 28 genes known to cause arRP or the related disease Leber congenital amaurosis (LCA). Cosegregation analyses were used to exclude possible causative genes from each of the 31 families. Bidirectional sequencing was used to identify disease-causing mutations in prioritized genes that were not excluded with cosegregation analyses. Results Two families were excluded from analysis due to identification of false paternity. An average of 28.9% of genes were excluded per family when only one affected individual was available, in contrast to an average of 71.4% or 89.8% of genes when either two, or three or more affected individuals were analyzed, respectively. A statistically significant relationship between the proportion of genes excluded and the number of affected individuals analyzed was identified using a multivariate regression model (p<0.0001). Subsequent DNA sequencing resulted in identification of the likely disease-causing gene as CRB1 in one family (c.2548 G>A) and USH2A in two families (c.2276 G>T). Conclusions This study has shown that SNP genotyping cosegregation analysis can be successfully used to refine and expedite the genetic characterization of arRP in a non-consanguineous population; however, this method is effective only when DNA samples are available from more than one affected individual.

Paterson, Rachel L.; McLaren, Terri L.; Hewitt, Alex W.; Hoffmann, Ling; Lamey, Tina M.

2012-01-01

146

Family-based designs in the age of large-scale gene-association studies  

Microsoft Academic Search

Both population-based and family-based designs are commonly used in genetic association studies to locate genes that underlie complex diseases. The simplest version of the family-based design — the transmission disequilibrium test — is well known, but the numerous extensions that broaden its scope and power are less widely appreciated. Family-based designs have unique advantages over population-based designs, as they are

Christoph Lange; Nan M. Laird

2006-01-01

147

The phenotypic expression of three MSH2 mutations in large Newfoundland families with Lynch syndrome  

Microsoft Academic Search

To compare the phenotypic expression of three different MSH2 mutations causing Lynch syndrome, 290 family members at 50% risk of inheriting a mutation were studied. Two truncating mutations\\u000a of the MSH2 gene have been identified in Newfoundland: an exon 8 deletion in five families (N=74 carriers) and an exon 4–16 deletion in one family (N=65 carriers). The third mutation was

Susan Stuckless; Patrick S. Parfrey; Michael O. Woods; Janet Cox; G. William Fitzgerald; Jane S. Green; Roger C. Green

2007-01-01

148

Contribution of large genomic BRCA1 alterations to early-onset breast cancer selected for family history and tumour morphology: a report from The Breast Cancer Family Registry  

PubMed Central

Introduction Selecting women affected with breast cancer who are most likely to carry a germline mutation in BRCA1 and applying the most appropriate test methodology remains challenging for cancer genetics services. We sought to test the value of selecting women for BRCA1 mutation testing on the basis of family history and/or breast tumour morphology criteria as well as the value of testing for large genomic alterations in BRCA1. Methods We studied women participating in the Breast Cancer Family Registry (BCFR), recruited via population-based sampling, who had been diagnosed with breast cancer before the age of 40 years who had a strong family history of breast or ovarian cancer (n = 187) and/or a first primary breast tumour with morphological features consistent with carrying a BRCA1 germline mutation (n = 133; 37 met both criteria). An additional 184 women diagnosed before the age of 40 years who had a strong family history of breast or ovarian cancer and who were not known to carry a germline BRCA1 mutation were selected from among women who had been recruited into the BCFR from clinical genetics services. These 467 women had been screened for BRCA1 germline mutations, and we expanded this testing to include a screen for large genomic BRCA1 alterations using Multiplex Ligation-dependent Probe Amplification. Results Twelve large genomic BRCA1 alterations were identified, including 10 (4%) of the 283 women selected from among the population-based sample. In total, 18 (12%), 18 (19%) and 16 (43%) BRCA1 mutations were identified in the population-based groups selected on the basis of family history only (n = 150), the group selected on the basis of tumour morphology only (n = 96) and meeting both criteria (n = 37), respectively. Conclusions Large genomic alterations accounted for 19% of all BRCA1 mutations identified. This study emphasises the value of combining information about family history, age at diagnosis and tumour morphology when selecting women for germline BRCA1 mutation testing as well as including a screen for large genomic alterations.

2011-01-01

149

Whole Exome Sequencing Identifies a Causal RBM20 Mutation in a Large Pedigree With Familial Dilated Cardiomyopathy.  

PubMed

Background- Whole exome sequencing is a powerful technique for Mendelian disease gene discovery. However, variant prioritization remains a challenge. We applied whole exome sequencing to identify the causal variant in a large family with familial dilated cardiomyopathy of unknown pathogenesis. Methods and Results- A large family with autosomal dominant, familial dilated cardiomyopathy was identified. Exome capture and sequencing were performed in 3 remotely related, affected subjects predicted to share <0.1% of their genomes by descent. Shared variants were filtered for rarity, evolutionary conservation, and predicted functional significance, and remaining variants were filtered against 71 locally generated exomes. Variants were also prioritized using the Variant Annotation Analysis and Search Tool. Final candidates were validated by Sanger sequencing and tested for segregation. There were 664 shared heterozygous nonsense, missense, or splice site variants, of which 26 were rare (minor allele frequency ?0.001 or not reported) in 2 public databases. Filtering against internal exomes reduced the number of candidates to 2, and of these, a single variant (c.1907 G>A) in RBM20, segregated with disease status and was absent in unaffected internal reference exomes. Bioinformatic prioritization with Variant Annotation Analysis and Search Tool supported this result. Conclusions- Whole exome sequencing of remotely related dilated cardiomyopathy subjects from a large, multiplex family, followed by systematic filtering, identified a causal RBM20 mutation without the need for linkage analysis. PMID:23861363

Wells, Quinn S; Becker, Jason R; Su, Yan R; Mosley, Jonathan D; Weeke, Peter; D'Aoust, Laura; Ausborn, Natalie L; Ramirez, Andrea H; Pfotenhauer, Jean P; Naftilan, Allen J; Markham, Larry; Exil, Vernat; Roden, Dan M; Hong, Charles C

2013-07-16

150

BoS : A Large and Diverse Family of Short Interspersed Elements (SINEs) in Brassica oleracea  

Microsoft Academic Search

Short interspersed elements (SINEs) are nonautonomous non-LTR retrotransposons that populate eukaryotic genomes. Numerous SINE families have been identified in animals, whereas only a few have been described in plants. Here we describe a new family of SINEs, named BoS, that is widespread in Brassicaceae and present at ~2000 copies in Brassica oleracea. In addition to sharing a modular structure and

Xiaoyu Zhang; Susan R. Wessler

2005-01-01

151

Trinucleotide expansions in the SCA7 gene in a large family with spinocerebellar ataxia and craniocervical dystonia  

Microsoft Academic Search

Spinocerebellar ataxia type 7 is a rare autosomal dominant cerebellar ataxia (ADCA). Herein, we describe the molecular and clinical findings in patients within six generations of a large Chinese family with spinocerebellar ataxia. To identify the genetic cause(s), 4 affected patients and 26 asymptomatic relatives were recruited for the study. Molecular screening of the SCA1 and SCA7 genes was carried

Yan Lin; Jia-Yong Zheng; Yan-Hui Jin; Yan-Chen Xie; Zi-Bing Jin

2008-01-01

152

Genetic heterogeneity and consanguinity lead to a "double hit": Homozygous mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa  

PubMed Central

Purpose Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP, hearing loss, and vestibular dysfunction. Methods The underlying cause of the appearance of syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family was studied with whole-genome homozygosity mapping followed by whole exome sequencing. Results The family was found to segregate novel mutations of two different genes: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B), which causes nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at a young age (9 months). However, this early diagnosis may be biased, as two of his older siblings had already been diagnosed, leading to increased awareness. At the age of 32 months, he had relatively good vision with normal visual fields. Further testing of visual function and structure at different ages in the three siblings is needed to determine whether the two RP-causing genes mutated in this youngest sibling confer increased disease severity. Conclusions This report further supports the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, this report provides a unique opportunity to study the clinical implications of the coexistence of pathogenic mutations in two RP-causative genes in a human patient.

Goldenberg-Cohen, Nitza; Banin, Eyal; Zalzstein, Yael; Cohen, Ben; Rotenstreich, Ygal; Rizel, Leah; Basel-Vanagaite, Lina

2013-01-01

153

Multicentric Castleman Disease in an HHV8-Infected Child Born to Consanguineous Parents With Systematic Review  

PubMed Central

Childhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection.

Moshous, Despina; Cassar, Olivier; Reguerre, Yves; Byun, Minji; Pedergnana, Vincent; Canioni, Danielle; Gessain, Antoine; Oksenhendler, Eric; Fieschi, Claire; Mahlaoui, Nizar; Riviere, Jean-Pierre; Herbigneaux, Rose-Marie; Muszlak, Matthias; Arnaud, Jean-Pierre; Fischer, Alain; Picard, Capucine; Blanche, Stephane; Plancoulaine, Sabine

2012-01-01

154

Reconstruction of Oomycete Genome Evolution Identifies Differences in Evolutionary Trajectories Leading to Present-Day Large Gene Families  

PubMed Central

The taxonomic class of oomycetes contains numerous pathogens of plants and animals but is related to nonpathogenic diatoms and brown algae. Oomycetes have flexible genomes comprising large gene families that play roles in pathogenicity. The evolutionary processes that shaped the gene content have not yet been studied by applying systematic tree reconciliation of the phylome of these species. We analyzed evolutionary dynamics of ten Stramenopiles. Gene gains, duplications, and losses were inferred by tree reconciliation of 18,459 gene trees constituting the phylome with a highly supported species phylogeny. We reconstructed a strikingly large last common ancestor of the Stramenopiles that contained ?10,000 genes. Throughout evolution, the genomes of pathogenic oomycetes have constantly gained and lost genes, though gene gains through duplications outnumber the losses. The branch leading to the plant pathogenic Phytophthora genus was identified as a major transition point characterized by increased frequency of duplication events that has likely driven the speciation within this genus. Large gene families encoding different classes of enzymes associated with pathogenicity such as glycoside hydrolases are formed by complex and distinct patterns of duplications and losses leading to their expansion in extant oomycetes. This study unveils the large-scale evolutionary dynamics that shaped the genomes of pathogenic oomycetes. By the application of phylogenetic based analyses methods, it provides additional insights that shed light on the complex history of oomycete genome evolution and the emergence of large gene families characteristic for this important class of pathogens.

Seidl, Michael F.; Van den Ackerveken, Guido; Govers, Francine; Snel, Berend

2012-01-01

155

Family dinner and disordered eating behaviors in a large cohort of adolescents.  

PubMed

We aimed to examine longitudinal associations between family dinner and disordered eating behaviors among adolescents. We studied 7535 females and 5913 males, 9 to 14 years of age in 1996. We performed multivariable logistic regression to assess the associations of previous year family dinner with 1-year incidence of each of 3 outcomes: purging, binge eating, and frequent dieting. Compared to those who ate family dinner "never or some days," female adolescents who ate family dinner at least most days were less likely to initiate purging, binge eating, and frequent dieting. Estimates of association among males were similar in direction and magnitude, although lower frequency of the outcomes resulted in less precise estimates and fewer statistically significant results. PMID:20390605

Haines, Jess; Gillman, Matthew W; Rifas-Shiman, Sheryl; Field, Alison E; Austin, S Bryn

156

Histone recognition and large-scale structural analysis of the human bromodomain family.  

PubMed

Bromodomains (BRDs) are protein interaction modules that specifically recognize ?-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family. PMID:22464331

Filippakopoulos, Panagis; Picaud, Sarah; Mangos, Maria; Keates, Tracy; Lambert, Jean-Philippe; Barsyte-Lovejoy, Dalia; Felletar, Ildiko; Volkmer, Rudolf; Müller, Susanne; Pawson, Tony; Gingras, Anne-Claude; Arrowsmith, Cheryl H; Knapp, Stefan

2012-03-30

157

Achieving patient and family engagement through the implementation and evolution of advisory councils across a large health care system.  

PubMed

Over the past decade, hospitals and health care systems have responded to the call for increased patient engagement and person-centered care. Organizations across the country have developed models and tools to assist in the effort toward patient and family engagement in health care delivery. In addition, current literature and trends suggest that patient satisfaction and quality outcomes are improved when patients and families become partners in their own health care and the delivery of that care. However, to formalize a patient-centric structure and process across a large health care system that is aimed at patient and family engagement can be a daunting activity. Utilizing well-established tools, Catholic Health Initiatives was successful in implementing the structures to deploy the ideas of patients and families in multiple facilities and care settings across 19 states. Nursing leaderships, in partnership with patients and their families within this health care delivery system, were the key contributors to the implementation of formalized patient and family advisory councils in hospitals across the enterprise. PMID:23744470

Haycock, Camille; Wahl, Carol

158

A Consanguinity Related Autosomal Translocation which Leads to Premature Ovarian Failure  

PubMed Central

The premature ovarian failures with underlying chromosomal abnormalities are normally X-linked, although their associations with the autosomal and the Robertsonian translocations are also possible. Here, we are reporting a case of premature ovarian failure which was associated with a translocation between the long arm of chromosome 7 at q11.23 and the short arm of chromosome 5 at p15.3. The proband was a 26-year-old Malay woman who presented with premature ovarian failure, who was referred for cytogenetic testing due to the suspicion of a chromosomal anomaly. Her physical examination revealed that she had no abdominal or pelvic masses and that she had normal secondary sexual characteristics. Her medical history as well, revealed no points for concern. However, a consanguineous relationship existed, as the patient’s paternal grandmother and maternal grandfather were biological cousins. Our present case indicated that region p15.3 of chromosome 5 and region q11.23 of chromosome 7 possibly carried essential genes for the ovarian function and that they postulated a link between the consanguinity and the chromosomal abnormalities.

Yik, Mot Yee; Zain, Murizah Mohd; Zakaria, Zubaidah; Yusoff, Narazah Mohd

2013-01-01

159

Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families  

PubMed Central

Introduction: A significant proportion of high-risk breast cancer families are not explained by mutations in known genes. Recent genome-wide searches (GWS) have not revealed any single major locus reminiscent of BRCA1 and BRCA2, indicating that still unidentified genes may explain relatively few families each or interact in a way obscure to linkage analyses. This has drawn attention to possible benefits of studying populations where genetic heterogeneity might be reduced. We thus performed a GWS for linkage on nine Icelandic multiple-case non-BRCA1/2 families of desirable size for mapping highly penetrant loci. To follow up suggestive loci, an additional 13 families from other Nordic countries were genotyped for selected markers. Methods: GWS was performed using 811 microsatellite markers providing about five centiMorgan (cM) resolution. Multipoint logarithm of odds (LOD) scores were calculated using parametric and nonparametric methods. For selected markers and cases, tumour tissue was compared to normal tissue to look for allelic loss indicative of a tumour suppressor gene. Results: The three highest signals were located at chromosomes 6q, 2p and 14q. One family contributed suggestive LOD scores (LOD 2.63 to 3.03, dominant model) at all these regions, without consistent evidence of a tumour suppressor gene. Haplotypes in nine affected family members mapped the loci to 2p23.2 to p21, 6q14.2 to q23.2 and 14q21.3 to q24.3. No evidence of a highly penetrant locus was found among the remaining families. The heterogeneity LOD (HLOD) at the 6q, 2p and 14q loci in all families was 3.27, 1.66 and 1.24, respectively. The subset of 13 Nordic families showed supportive HLODs at chromosome 6q (ranging from 0.34 to 1.37 by country subset). The 2p and 14q loci overlap with regions indicated by large families in previous GWS studies of breast cancer. Conclusions: Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.

2010-01-01

160

A large duplication in LIPH underlies autosomal recessive hypotrichosis simplex in four Middle Eastern families.  

PubMed

Autosomal recessive hypotrichosis simplex (ARHS) manifests with paucity of hair appearing during early childhood. We assessed four affected families. We initially genotyped three of these families for a panel of microsatellite markers spanning all ARHS-associated loci and obtained data suggesting linkage to 3q27, encompassing LIPH, which had previously been shown to be associated with ARHS. Accordingly, a homozygous duplication mutation in exon 2 of this gene (c.280_369dup; p.Gly94_Lys123dup) was found to segregate with the disease in all the families. Through the identification of the first duplication mutation in the human LIPH gene, we provide further evidence supporting a role for the phospholipase signalling pathway in hair growth and differentiation. PMID:18820939

Nahum, Sagi; Pasternack, Sandra M; Pforr, Jana; Indelman, Margarita; Wollnik, Bernd; Bergman, Reuven; Nöthen, Markus M; König, Arne; Khamaysi, Ziyad; Betz, Regina C; Sprecher, Eli

2008-09-27

161

Aquaporins Constitute a Large and Highly Divergent Protein Family in Maize  

Microsoft Academic Search

Aquaporins (AQPs) are an ancient family of channel proteins that transport water and neutral solutes through a pore and are found in all eukaryotes and most prokaryotes. A comparison of the amino acid sequences and phylogenetic analysis of 31 full-length cDNAs of maize (Zea mays) AQPs shows that they comprise four different groups of highly divergent proteins. We have classified

Francois Chaumont; Francois Barrieu; Eva Wojcik; Maarten J. Chrispeels; Rudolf Jung

2001-01-01

162

Intracellular Positioning of Isoforms Explains an Unusually Large Adenylate Kinase Gene Family in the Parasite  

Microsoft Academic Search

Adenylate kinases occur classically as cytoplasmic and mitochondrial enzymes, but the expression of seven adenylate kinases in the flagellated protozoan parasite Trypanosoma brucei (order, Kinetoplastida; family, Trypanosomatidae) easily exceeds the number of isoforms previously observed within a single cell and raises questions as to their location and function. We show that a requirement to target adenylate kinase into glycosomes, which

Michael L. Ginger; E. Solange Ngazoa; Claudio A. Pereira; Timothy J. Pullen; Mostafa Kabiri; Katja Becker; Dietmar Steverdingc

163

A novel deletion in TNNI2 causes distal arthrogryposis in a large Chinese family with marked variability of expression  

Microsoft Academic Search

Distal arthrogryposis (DA) is composed of a group of clinically and genetically heterogeneous disorders, characterized by multiple congenital contractures of the limbs. Point mutations in three genes encoding contractile fast-twitch myofibers, TPM2, TNNI2 and TNNT3, were recently identified in DA type 1 (DA1; MIM 108120) and DA type 2B (DA2B; MIM 601680). We have described a large Chinese DA family

Miao Jiang; Xiuli Zhao; Weitian Han; Chaoying Bian; Xuefu Li; Ge Wang; Yang Ao; Yunqing Li; Dongxu Yi; Yang Zhe; Wilson H. Y. Lo; Xue Zhang; Jianxin Li

2006-01-01

164

Ovarian dysfunction and FMR1 alleles in a large Italian family with POF and FRAXA disorders: case report  

Microsoft Academic Search

BACKGROUND: The association between premature ovarian failure (POF) and the FMR1 repeat number (41> CGGnFMR1 alleles. CASE PRESENTATION: We describe the coexistence in a large Italian kindred of Fragile X syndrome and familial POF in females with ovarian dysfunctions who carried normal or expanded FMR1 alleles. Genetic analysis of the FMR1 gene in over three generations of females revealed that

Maria Giuseppina Miano; Carmela Laperuta; Pietro Chiurazzi; Michele D'Urso; Matilde Valeria Ursini

2007-01-01

165

A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails  

Microsoft Academic Search

BACKGROUND: Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD. METHODS: Here, a large Chinese family with CCD and hyperplastic nails was recruited. The clinical features displayed a significant intrafamilial variation.

Shaohua Tang; Qiyu Xu; Xueqin Xu; Jicheng Du; Xuemei Yang; Yusheng Jiang; Xiaoqin Wang; Nancy Speck; Taosheng Huang

2007-01-01

166

A Moroccan family with autosomal recessive sensorineural hearing loss caused by a mutation in the gap junction protein gene connexin 26 (GJB2)  

Microsoft Academic Search

We report a mutation in the connexin 26 gene (Cx26) in a consanguineous Moroccan family linked to the DFNA3\\/DFNB1 locus on human chromosome 13q11-q12. Affected subjects display congenital, bilateral, sensorineural hearing loss. We have previously identified Cx26 mutations in consanguineous Pakistani families. This current finding indicates that Cx26 mutations are not restricted to ethnically and geographically distinct populations. This is

N J Lench; A F Markham; R F Mueller; D P Kelsell; R J Smith; P J Willems; I Schatteman; H Capon; P J Van De Heyning; G Van Camp

1998-01-01

167

Alcohol-responsive myoclonic dystonia in a large family: dominant inheritance and phenotypic variation.  

PubMed

Alcohol-responsive myoclonic dystonia is reported in 26 individuals in a six-generation family, thus indicating autosomal dominant inheritance. Twenty affected family members aged between 3 and 56 years were examined on one occasion. Myoclonus in arms, shoulder, and neck distribution was seen in 17, with occasional generalized jerks in 14. Leg dystonia/hemidystonia was seen in two infant cases, writer's cramp in seven, torticollis/retrocollis in two, and finger tremor in three. The onset of myoclonus was regularly reported from 2 to 3 years of age, the onset of leg dystonia/hemidystonia from 6 to 18 months of age, writer's cramp from early school age, and neck dystonia from late teenage. The effect of alcohol had been noted in 10 individuals, and seven of them abused alcohol. Once established, the neurological signs did not progress significantly. Leg dystonia resolved in two juvenile members. Two adult members had recovered from myoclonus: one elderly man and one posthemorrhagic spastic hemiplegic man. Extensive family investigation is necessary to clarify the clinical variation of this autosomal dominant disorder of involuntary movements. PMID:2259350

Kyllerman, M; Forsgren, L; Sanner, G; Holmgren, G; Wahlström, J; Drugge, U

1990-01-01

168

Evolution of a Large, Conserved, and Syntenic Gene Family in Insects  

PubMed Central

The Osiris gene family, first described in Drosophila melanogaster, is clustered in the genomes of all Drosophila species sequenced to date. In D. melanogaster, it explains the enigmatic phenomenon of the triplo-lethal and haploinsufficient locus Tpl. The synteny of Osiris genes in flies is well conserved, and it is one of the largest syntenic blocks in the Drosophila group. By examining the genome sequences of other insects in a wide range of taxonomic orders, we show here that the gene family is well-conserved and syntenic not only in the diptera but across the holometabolous and hemimetabolous insects. Osiris gene homologs have also been found in the expressed sequence tag sequences of various other insects but are absent from all groups that are not insects, including crustacea and arachnids. It is clear that the gene family evolved by gene duplication and neofunctionalization very soon after the divergence of the insects from other arthropods but before the divergence of the insects from one another and that the sequences and synteny have been maintained by selection ever since.

Shah, Neethu; Dorer, Douglas R.; Moriyama, Etsuko N.; Christensen, Alan C.

2012-01-01

169

Aspects of pre-eclamptic toxaemia of pregnancy, consanguinity, twinning in Ankara.  

PubMed Central

It appears that women classed as having pre-eclamptic toxaemia are less frequently consanguineous with their husbands than all other mothers and in particular those mothers classed as having pregnancies complicated by chronic hypertensive disease. Search revealed no evidence for possible biases which could have stimulated such findings. Further evidence is advanced suggesting that, though pre-eclamptic toxaemia is more common in all types of twin pregnancies than in single births, it is more common where the twins are dizygous than where they are monozygous. It is pointed out that both these findings would be expected if there was a contribution to the aetiology of pre-eclamptic toxaemia by maternal/fetal immunological incompatibility. However, if such a mechanism exists it is not always determined at the same gene locus.

Stevenson, A C; Say, B; Ustaoglu, S; Durmus, Z

1976-01-01

170

Large scale genotype-phenotype analyses indicate that novel prognostic tools are required for families with facioscapulohumeral muscular dystrophy  

PubMed Central

Facioscapulohumeral muscular dystrophy has been genetically linked to reduced numbers (?8) of D4Z4 repeats at 4q35 combined with 4A(159/161/168) DUX4 polyadenylation signal haplotype. However, we have recently reported that 1.3% of healthy individuals carry this molecular signature and 19% of subjects affected by facioscapulohumeral muscular dystrophy do not carry alleles with eight or fewer D4Z4 repeats. Therefore, prognosis for subjects carrying or at risk of carrying D4Z4 reduced alleles has become more complicated. To test for additional prognostic factors, we measured the degree of motor impairment in a large group of patients affected by facioscapulohumeral muscular dystrophy and their relatives who are carrying D4Z4 reduced alleles. The clinical expression of motor impairment was assessed in 530 subjects, 163 probands and 367 relatives, from 176 unrelated families according to a standardized clinical score. The associations between clinical severity and size of D4Z4 allele, degree of kinship, gender, age and 4q haplotype were evaluated. Overall, 32.2% of relatives did not display any muscle functional impairment. This phenotype was influenced by the degree of relation with proband, because 47.1% of second- through fifth-degree relatives were unaffected, whereas only 27.5% of first-degree family members did not show motor impairment. The estimated risk of developing motor impairment by age 50 for relatives carrying a D4Z4 reduced allele with 1–3 repeats or 4–8 repeats was 88.7% and 55%, respectively. Male relatives had a mean score significantly higher than females (5.4 versus 4.0, P = 0.003). No 4q haplotype was exclusively associated with the presence of disease. In 13% of families in which D4Z4 alleles with 4–8 repeats segregate, the diagnosis of facioscapulohumeral muscular dystrophy was reported only in one generation. In conclusion, this large-scale analysis provides further information that should be taken into account when counselling families in which a reduced allele with 4–8 D4Z4 repeats segregates. In addition, the reduced expression of disease observed in distant relatives suggests that a family’s genetic background plays a role in the occurrence of facioscapulohumeral muscular dystrophy. These results indicate that the identification of new susceptibility factors for this disease will require an accurate classification of families.

Scionti, Isabella; Sera, Francesco; Govi, Monica; D'Amico, Roberto; Frambolli, Ilaria; Mele, Fabiano; Filosto, Massimiliano; Vercelli, Liliana; Ruggiero, Lucia; Berardinelli, Angela; Angelini, Corrado; Antonini, Giovanni; Bucci, Elisabetta; Cao, Michelangelo; Daolio, Jessica; Di Muzio, Antonio; Di Leo, Rita; Galluzzi, Giuliana; Iannaccone, Elisabetta; Maggi, Lorenzo; Maruotti, Valerio; Moggio, Maurizio; Mongini, Tiziana; Morandi, Lucia; Nikolic, Ana; Pastorello, Ebe; Ricci, Enzo; Rodolico, Carmelo; Santoro, Lucio; Servida, Maura; Siciliano, Gabriele; Tomelleri, Giuliano

2013-01-01

171

Ovarian dysfunction and FMR1 alleles in a large Italian family with POF and FRAXA disorders: case report  

PubMed Central

Background The association between premature ovarian failure (POF) and the FMR1 repeat number (41> CGGn< 200) has been widely investigated. Current findings suggest that the risk estimation for POF can be calculated in the offspring of women with pre-mutated FMR1 alleles. Case presentation We describe the coexistence in a large Italian kindred of Fragile X syndrome and familial POF in females with ovarian dysfunctions who carried normal or expanded FMR1 alleles. Genetic analysis of the FMR1 gene in over three generations of females revealed that six carried pre-mutated alleles (61–200), of which two were also affected by POF. However a young woman, who presented a severe ovarian failure with early onset, carried normal FMR1 alleles (<40). The coexistence within the same family of two dysfunctional ovarian conditions, one FMR1-related and one not FMR1-related, suggests that the complexity of familial POF conditions is larger than expected. Conclusion Our case study represents a helpful observation and will provide familial cases with heterogeneous etiology that could be further studied when candidate genes in addition to the FMR1 premutation will be available.

Miano, Maria Giuseppina; Laperuta, Carmela; Chiurazzi, Pietro; D'Urso, Michele; Ursini, Matilde Valeria

2007-01-01

172

Myotonia congenita with strabismus in a large family with a mutation in the SCN4A gene  

PubMed Central

Background/Aims To determine the genetic basis of myotonia congenita (MC) and strabismus in a large Caucasian family. Methods Seven patients making up four generations of a family with MC and strabismus were recruited. All patients had at least one standard ophthalmic examination, including best-corrected visual acuity, refraction, and ocular motility measurements. CLCN1 and SCN4A genes were sequenced and analysed for mutations. Results Five out of the seven family members were diagnosed with MC by clinical history and electromyography. Ophthalmic history and exam revealed eyelid myotonia and strabismus. All patients with MC were diagnosed with strabismus between the ages of 3 and 6 and required surgical restoration of ocular alignment. Sequencing results revealed a c. 1333G>A; p. Val445Met mutation in the SCN4A gene. Conclusion There are few reports describing eyelid myotonia and strabismus in patients diagnosed with MC. We found significant ocular involvement in a family with a mutation in SCN4A. Future studies may confirm that MC with significant ocular involvement can be used to direct genetic analysis.

Du, H; Grob, S R; Zhao, L; Lee, J; El-Sahn, M; Hughes, G; Luo, J; Schaf, K; Duan, Y; Quach, J; Wei, X; Shaw, P; Granet, D; Zhang, K

2012-01-01

173

Impact of new genomic tools on the practice of clinical genetics in consanguineous populations: the Saudi experience.  

PubMed

Consanguinity is practiced by around one tenth of the world population but its global distribution is far from uniform. In countries where consanguinity is common, a corresponding increase in the frequency of autosomal recessive diseases is usually observed owing to increased risk of homozygosity for ancestral haplotypes (autozygosity or identity by descent) that harbor pathogenic alleles. The burden of these diseases becomes more apparent as the healthcare system makes gains in its fight against communicable diseases in these countries. Recent advances in molecular genetics make it possible to leverage the mechanism by which consanguinity predisposes to the occurrence of autosomal recessive diseases in order to uncover the causal mutations at an efficient and cost-effective way compared to outbred populations. The identification of these mutations at an unprecedented scale has the potential to significantly reshape the practice of clinical genetics in these populations and to offer opportunities for innovative public health policies. This review discusses the impact that new genomic tools have had on a sample patient population and how they can inform future public health policies in ways that might be relevant to other consanguineous populations. PMID:23451714

Alkuraya, F S

2013-03-17

174

Nonimmune hydrops fetalis in two cases of consanguineous parents and associated with hereditary spherocytosis and hemophagocytic hystiocytosis  

Microsoft Academic Search

Nonimmune hydrops fetalis may occur as a result of different etiological conditions and in about one-third of cases no cause could be identified. Here, we report two cases of nonimmune hydrops fetalis associated with hereditary spherocytosis and hemophagocytic hystiocytosis. We think that babies with hydrops fetalis born of consanguineous parents should be examined for hereditary diseases, and that these rare

S Yetgin; S Aytac; F Gurakan; M Yurdakok

2007-01-01

175

Autoimmune Thyroiditis and Diabetes: Dissecting the Joint Genetic Susceptibility in a Large Cohort of Multiplex Families  

PubMed Central

Context: Epidemiological data support a shared genetic susceptibility to autoimmune thyroid disease (AITD) and type 1 diabetes (T1D). Both diseases frequently occur within the same family and in the same individual. Patients developing both T1D and AITD are considered to have an autoimmune polyglandular syndrome type 3 variant (APS3v). Objective: The goals of this study were to identify the joint susceptibility loci/genes for T1D and AITD. Settings: The study was conducted at an academic medical center. Participants and Main Outcome Measures: We used whole genome and candidate gene approaches in a data set of 88 families multiplex for T1D and AITD (448 individuals). Results: We identified three loci, on chromosomes 2p, 6p, and Xp, showing linkage when individuals with either T1D or AITD were classified as affected. The 6p locus contained the human leukocyte antigen class II genes, and the Xp locus contained the FOXP3 gene. Three loci, on 2q, 6p (human leukocyte antigen class II), and Xp, showed evidence for linkage when only APS3v individuals (T1D+AITD) were classified as affected. Analysis of positional candidate genes strongly supported CTLA-4 as the gene on 2q associated with APS3v and FOXP3 as the gene on Xp associated with T1D or AITD and APS3v. In addition, the PTPN22 and insulin variable number tandem repeat genes showed significant associations with T1D or AITD in our families. Conclusions: Our results demonstrate a strong shared genetic susceptibility to T1D and AITD, with most shared genes involved in immune regulation, suggesting that immune dysregulation plays an important role in the joint susceptibility to T1D and AITD.

Villano, Maria Justina B.; Huber, Amanda K.; Greenberg, David A.; Golden, Brian K.; Concepcion, Erlinda; Tomer, Yaron

2009-01-01

176

An efficient parallel approach for identifying protein families in large-scale metagenomic data sets  

Microsoft Academic Search

Metagenomics is the study of environmental microbial communities using state-of-the-art genomic tools. Recent advancements in high-throughput technologies have enabled the accumulation of large volumes of metagenomic data that was until a couple of years back was deemed impractical for generation. A primary bottleneck, however, is in the lack of scalable algorithms and open source software for large-scale data processing. In

Changjun Wu; Ananth Kalyanaraman

2008-01-01

177

Evaluating the feasibility of using candidate DNA barcodes in discriminating species of the large Asteraceae family  

Microsoft Academic Search

BACKGROUND: Five DNA regions, namely, rbcL, matK, ITS, ITS2, and psbA-trnH, have been recommended as primary DNA barcodes for plants. Studies evaluating these regions for species identification in the large plant taxon, which includes a large number of closely related species, have rarely been reported. RESULTS: The feasibility of using the five proposed DNA regions was tested for discriminating plant

Ting Gao; Hui Yao; Jingyuan Song; Yingjie Zhu; Chang Liu; Shilin Chen

2010-01-01

178

Study of large inbred Friedreich ataxia families reveals a recombination between D9S15 and the disease locus  

SciTech Connect

Friedreich ataxia is a neurodegenerative disorder with autosomal recessive inheritance. Precise linkage mapping of the Friedreich ataxia locus (FRDA) in 9q13-q21 should lead to the isolation of the defective gene by positional cloning. The two closest DNA markers, D9S5 and D9S15, show very tight linkage to FRDA, making difficult the ordering of the three loci. The authors present a linkage study of three large Friedreich ataxia families of Tunisian origin, with several multiallelic markers around D9S5 and D9S15. Haplotype data were used to investigate genetic homogeneity of the disease in these geographically related families. A meiotic recombination was found in a nonaffected individual, which excludes a 150-kb segment, including D9S15, as a possible location for the Freidreich ataxia gene and which should orient the search in the D9S5 region. 16 refs., 1 fig., 1 tab.

Belal, S.; Ben Hamida, C.; Hentati, F.; Ben Hamida, M. (Institut National de Neurologie, Tunis (Tunisia)); Panayides, K.; Ioannou, P.; MIddleton, L.T. (Cyprus Inst. of Neurology and Genetics, Nicosia (Cyprus)); Sirugo, G.; Koenig, S.; Mandel, J.L (LGME-CNRS, Strasbourg (France)); Beckmann, J. (Centre d'Etudes du Polymorphisme Humain, Paris (France))

1992-12-01

179

Bracoviruses Contain a Large Multigene Family Coding for Protein Tyrosine Phosphatases  

PubMed Central

The relationship between parasitic wasps and bracoviruses constitutes one of the few known mutualisms between viruses and eukaryotes. The virions produced in the wasp ovaries are injected into host lepidopteran larvae, where virus genes are expressed, allowing successful development of the parasite by inducing host immune suppression and developmental arrest. Bracovirus-bearing wasps have a common phylogenetic origin, and contemporary bracoviruses are hypothesized to have been inherited by chromosomal transmission from a virus that originally integrated into the genome of the common ancestor wasp living 73.7 ± 10 million years ago. However, so far no conserved genes have been described among different braconid wasp subfamilies. Here we show that a gene family is present in bracoviruses of different braconid wasp subfamilies (Cotesia congregata, Microgastrinae, and Toxoneuron nigriceps, Cardiochilinae) which likely corresponds to an ancient component of the bracovirus genome that might have been present in the ancestral virus. The genes encode proteins belonging to the protein tyrosine phosphatase family, known to play a key role in the control of signal transduction pathways. Bracovirus protein tyrosine phosphatase genes were shown to be expressed in different tissues of parasitized hosts, and two protein tyrosine phosphatases were produced with recombinant baculoviruses and tested for their biochemical activity. One protein tyrosine phosphatase is a functional phosphatase. These results strengthen the hypothesis that protein tyrosine phosphatases are involved in virally induced alterations of host physiology during parasitism.

Provost, Bertille; Varricchio, Paola; Arana, Eloisa; Espagne, Eric; Falabella, Patrizia; Huguet, Elisabeth; La Scaleia, Raffaella; Cattolico, Laurence; Poirie, Marylene; Malva, Carla; Olszewski, Julie A.; Pennacchio, Francesco; Drezen, Jean-Michel

2004-01-01

180

Large scale genotype-phenotype analyses indicate that novel prognostic tools are required for families with facioscapulohumeral muscular dystrophy.  

PubMed

Facioscapulohumeral muscular dystrophy has been genetically linked to reduced numbers (?8) of D4Z4 repeats at 4q35 combined with 4A(159/161/168) DUX4 polyadenylation signal haplotype. However, we have recently reported that 1.3% of healthy individuals carry this molecular signature and 19% of subjects affected by facioscapulohumeral muscular dystrophy do not carry alleles with eight or fewer D4Z4 repeats. Therefore, prognosis for subjects carrying or at risk of carrying D4Z4 reduced alleles has become more complicated. To test for additional prognostic factors, we measured the degree of motor impairment in a large group of patients affected by facioscapulohumeral muscular dystrophy and their relatives who are carrying D4Z4 reduced alleles. The clinical expression of motor impairment was assessed in 530 subjects, 163 probands and 367 relatives, from 176 unrelated families according to a standardized clinical score. The associations between clinical severity and size of D4Z4 allele, degree of kinship, gender, age and 4q haplotype were evaluated. Overall, 32.2% of relatives did not display any muscle functional impairment. This phenotype was influenced by the degree of relation with proband, because 47.1% of second- through fifth-degree relatives were unaffected, whereas only 27.5% of first-degree family members did not show motor impairment. The estimated risk of developing motor impairment by age 50 for relatives carrying a D4Z4 reduced allele with 1-3 repeats or 4-8 repeats was 88.7% and 55%, respectively. Male relatives had a mean score significantly higher than females (5.4 versus 4.0, P = 0.003). No 4q haplotype was exclusively associated with the presence of disease. In 13% of families in which D4Z4 alleles with 4-8 repeats segregate, the diagnosis of facioscapulohumeral muscular dystrophy was reported only in one generation. In conclusion, this large-scale analysis provides further information that should be taken into account when counselling families in which a reduced allele with 4-8 D4Z4 repeats segregates. In addition, the reduced expression of disease observed in distant relatives suggests that a family's genetic background plays a role in the occurrence of facioscapulohumeral muscular dystrophy. These results indicate that the identification of new susceptibility factors for this disease will require an accurate classification of families. PMID:24030947

Ricci, Giulia; Scionti, Isabella; Sera, Francesco; Govi, Monica; D'Amico, Roberto; Frambolli, Ilaria; Mele, Fabiano; Filosto, Massimiliano; Vercelli, Liliana; Ruggiero, Lucia; Berardinelli, Angela; Angelini, Corrado; Antonini, Giovanni; Bucci, Elisabetta; Cao, Michelangelo; Daolio, Jessica; Di Muzio, Antonio; Di Leo, Rita; Galluzzi, Giuliana; Iannaccone, Elisabetta; Maggi, Lorenzo; Maruotti, Valerio; Moggio, Maurizio; Mongini, Tiziana; Morandi, Lucia; Nikolic, Ana; Pastorello, Ebe; Ricci, Enzo; Rodolico, Carmelo; Santoro, Lucio; Servida, Maura; Siciliano, Gabriele; Tomelleri, Giuliano; Tupler, Rossella

2013-09-11

181

Age distribution of human gene families shows significant roles of both large- and small-scale duplications in vertebrate evolution.  

PubMed

The classical (two-round) hypothesis of vertebrate genome duplication proposes two successive whole-genome duplication(s) (polyploidizations) predating the origin of fishes, a view now being seriously challenged. As the debate largely concerns the relative merits of the 'big-bang mode' theory (large-scale duplication) and the 'continuous mode' theory (constant creation by small-scale duplications), we tested whether a significant proportion of paralogous genes in the contemporary human genome was indeed generated in the early stage of vertebrate evolution. After an extensive search of major databases, we dated 1,739 gene duplication events from the phylogenetic analysis of 749 vertebrate gene families. We found a pattern characterized by two waves (I, II) and an ancient component. Wave I represents a recent gene family expansion by tandem or segmental duplications, whereas wave II, a rapid paralogous gene increase in the early stage of vertebrate evolution, supports the idea of genome duplication(s) (the big-bang mode). Further analysis indicated that large- and small-scale gene duplications both make a significant contribution during the early stage of vertebrate evolution to build the current hierarchy of the human proteome. PMID:12032571

Gu, Xun; Wang, Yufeng; Gu, Jianying

2002-05-28

182

Intense paramagnon excitations in a large family of high-temperature superconductors  

Microsoft Academic Search

In the search for the mechanism of high-temperature superconductivity, intense research has been focused on the evolution of the spin excitation spectrum on doping from the antiferromagnetic insulating to the superconducting state of the cuprates. Because of technical limitations, the experimental investigation of doped cuprates has been largely focused on low-energy excitations in a small range of momentum space. Here

M. Le Tacon; G. Ghiringhelli; J. Chaloupka; M. Moretti Sala; V. Hinkov; M. W. Haverkort; M. Minola; M. Bakr; K. J. Zhou; S. Blanco-Canosa; C. Monney; Y. T. Song; G. L. Sun; C. T. Lin; G. M. de Luca; M. Salluzzo; G. Khaliullin; T. Schmitt; L. Braicovich; B. Keimer

2011-01-01

183

Evolution of a large ribosomal RNA multigene family in filamentous fungi: Birth and death of a concerted evolution paradigm  

PubMed Central

In eukaryotes, the primary components of the ribosome are encoded by multicopy nuclear ribosomal RNA (rRNA) genes: 28/26S, 18S, 5.8S, and 5S. Copies of these genes are typically localized within tandem arrays and homogenized within a genome. As a result, nuclear rRNA gene families have become a paradigm of concerted evolution. In filamentous fungi of the subphylum Pezizomycotina, 5S rRNA genes exist as a large and dispersed multigene family, with between 50 and 100 copies per genome. To determine whether these genes defy the concerted evolution paradigm, we examined the patterns of evolution of these genes by using sequences from the complete genomes of four species. Analyses of these sequences revealed (i) multiple 5S gene types within a genome, (ii) interspecies clustering of gene types, (iii) multiple identical gene types shared among species, (iv) multiple pseudogenes within a genome, and (v) presence/absence variation of individual 5S copies in comparisons of closely related species. These results demonstrate that the 5S family in these species is characterized by birth-and-death evolution under strong purifying selection. Furthermore, our results suggest that birth-and-death evolution occurs at different rates in the genera examined, and that the multiplication and movement of 5S genes across the genome are highly dynamic. As such, we hypothesize that a mechanism resembling retroposition controls 5S rRNA gene amplification, dispersal, and integration in the genomes of filamentous fungi.

Rooney, Alejandro P.; Ward, Todd J.

2005-01-01

184

Molecular analysis of recombination in a family with Duchenne muscular dystrophy and a large pericentric X chromosome inversion  

SciTech Connect

It has been demonstrated in animal studies that, in animals heterozygous for pericentric chromosomal inversions, loop formation is greatly reduced during meiosis. This results in absence of recombination within the inverted segment, with recombination seen only outside the inversion. A recent study in yeast has shown that telomeres, rather than centromeres, lead in chromosome movement just prior to meiosis and may be involved in promoting recombination. We studied by cytogenetic analysis and DNA polymorphisms the nature of meiotic recombination in a three-generation family with a large pericentric X chromosome inversion, inv(X)(p21.1q26), in which Duchenne muscular dystrophy (DMD) was cosegregating with the inversion. On DNA analysis there was no evidence of meiotic recombination between the inverted and normal X chromosomes in the inverted segment. Recombination was seen at the telomeric regions, Xp22 and Xq27-28. No deletion or point mutation was found on analysis of the DMD gene. On the basis of the FISH results, we believe that the X inversion is the mutation responsible for DMD in this family. Our results indicate that (1) pericentric X chromosome inversions result in reduction of recombination between the normal and inverted X chromosomes; (2) meiotic X chromosome pairing in these individuals is likely initiated at the telomeres; and (3) in this family DMD is caused by the pericentric inversion. 50 refs., 7 figs., 1 tab.

Shashi, V.; Golden, W.L.; Allinson, P.S. [Univ. of Virginia Health Sciences Center, Charlottesville, VA (United States)] [and others

1996-06-01

185

Consanguinity in Centre d'?tude du Polymorphisme Humain (CEPH) pedigrees  

PubMed Central

A set of Centre d'Étude du Polymorphisme Humain (CEPH) cell lines serves as a large reference collection that has been widely used as a benchmark for allele frequencies in the analysis of genetic variants, to create linkage maps of the human genome, to study the genetics of gene expression, to provide samples to the HapMap and 1000 Genomes projects, and for a variety of other applications. An explicit feature of the CEPH collection is that these multigenerational families represent reference panels of known relatedness, consisting mostly of three-generation pedigrees with large sibships, two parents, and grandparents. We applied identity-by-state (IBS) and identity-by-descent (IBD) methods to high-density genotype data from 186 CEPH individuals in 13 families. We identified unexpected relatedness between nominally unrelated grandparents both within and between pedigrees. For one pair, the estimated Cotterman coefficient of relatedness k1 exceeded 0.2, consistent with one-eighth sharing (eg, first-cousins). Unexpectedly, significant IBD2 values were discovered in both second-degree and parent–child relationships. These were accompanied by regions of homozygosity in the offspring, which corresponded to blocks lacking IBS0 in purportedly unrelated parents, consistent with inbreeding. Our findings support and extend a 1999 report, based on the use of short tandem-repeat polymorphisms, that several CEPH families had regions of homozygosity consistent with autozygosity. We benchmarked our IBD approach (called kcoeff) against both RELPAIR and PREST software packages. Our findings may affect the interpretation of previous studies and the design of future studies that rely on the CEPH resource.

Stevens, Eric L; Heckenberg, Greg; Baugher, Joseph D; Roberson, Elisha DO; Downey, Thomas J; Pevsner, Jonathan

2012-01-01

186

Consanguinity in Centre d'Étude du Polymorphisme Humain (CEPH) pedigrees.  

PubMed

A set of Centre d'Étude du Polymorphisme Humain (CEPH) cell lines serves as a large reference collection that has been widely used as a benchmark for allele frequencies in the analysis of genetic variants, to create linkage maps of the human genome, to study the genetics of gene expression, to provide samples to the HapMap and 1000 Genomes projects, and for a variety of other applications. An explicit feature of the CEPH collection is that these multigenerational families represent reference panels of known relatedness, consisting mostly of three-generation pedigrees with large sibships, two parents, and grandparents. We applied identity-by-state (IBS) and identity-by-descent (IBD) methods to high-density genotype data from 186 CEPH individuals in 13 families. We identified unexpected relatedness between nominally unrelated grandparents both within and between pedigrees. For one pair, the estimated Cotterman coefficient of relatedness k1 exceeded 0.2, consistent with one-eighth sharing (eg, first-cousins). Unexpectedly, significant IBD2 values were discovered in both second-degree and parent-child relationships. These were accompanied by regions of homozygosity in the offspring, which corresponded to blocks lacking IBS0 in purportedly unrelated parents, consistent with inbreeding. Our findings support and extend a 1999 report, based on the use of short tandem-repeat polymorphisms, that several CEPH families had regions of homozygosity consistent with autozygosity. We benchmarked our IBD approach (called kcoeff) against both RELPAIR and PREST software packages. Our findings may affect the interpretation of previous studies and the design of future studies that rely on the CEPH resource. PMID:22274586

Stevens, Eric L; Heckenberg, Greg; Baugher, Joseph D; Roberson, Elisha D O; Downey, Thomas J; Pevsner, Jonathan

2012-01-25

187

A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet-Biedl syndrome in a Pakistani family.  

PubMed

Bardet-Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet-Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet-Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet-Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease. Homozygous regions obtained from SNP array depicted three known genes BBS10, BBS14 and BBS2. Bidirectional sequencing of all coding exons by traditional sequencing of all these three genes showed a homozygous deletion of 10 nucleotides (c.1958_1967del), in BBS10 in both affected brothers. The segregation analysis revealed that the parents, paternal grandfather, maternal grandmother and an unaffected sister were heterozygous for the deletion. Such a large deletion in BBS10 has not been reported previously in any population and is likely to be contributing to the phenotype of Bardet-Biedl Syndrome in this family. PMID:23403234

Agha, Zehra; Iqbal, Zafar; Azam, Maleeha; Hoefsloot, Lies H; van Bokhoven, Hans; Qamar, Raheel

2013-02-09

188

Phenotypic variability in a large Czech family with a dynamin 2-associated Charcot-Marie-Tooth neuropathy.  

PubMed

Mutations in the Dynamin 2 gene (DNM2) cause autosomal dominant centronuclear myopathy or autosomal dominant (AD) Charcot-Marie-Tooth (CMT) disease. Here the authors report one large Czech family with 15 members affected with an AD CMT phenotype of extraordinary variability. Genetic linkage analysis using SNP arrays revealed a locus of about 9.6 Mb on chromosome 19p13.1-13.2. In this critical interval, 373 genes were located. The only gene herein known to be associated with an intermediate type of CMT was Dynamin 2 (DNM2). Subsequent sequence analysis of the DNM2 gene in the index patient revealed a novel missense mutation p.Met580Thr. This missense mutation segregated with the neuropathy, indicating the causal character of this mutation. The phenotype of CMT in this family shows mild to moderate impairment with relatively preserved upper limbs and a very broad range of the onset of clinical symptoms from an early onset around the age of 12 to the late onset during the fifth decade. Electrophysiology showed an intermediate type of peripheral neuropathy. The motor median nerve conduction velocity varied from 36 m/s to normal values with signs of asymmetrical affection of peripheral nerves. No additional symptoms such as cranial nerve involvement, cataract, and signs of neutropenia or myopathy syndrome were observed in any member of the family yet. The progression was slow with no loss of ambulation. The authors suggest that the characterization of clinical variability in a single family may help to direct the genetic analysis directly to the rarely observed DNM2 mutations. PMID:22091729

Haberlová, J; Mazanec, R; Ridzo?, P; Baránková, L; Nürnberg, G; Nürnberg, P; Sticht, H; Huehne, K; Seeman, P; Rautenstrauss, B

2011-12-01

189

MPI-PHYLIP: Parallelizing Computationally Intensive Phylogenetic Analysis Routines for the Analysis of Large Protein Families  

PubMed Central

Background Phylogenetic study of protein sequences provides unique and valuable insights into the molecular and genetic basis of important medical and epidemiological problems as well as insights about the origins and development of physiological features in present day organisms. Consensus phylogenies based on the bootstrap and other resampling methods play a crucial part in analyzing the robustness of the trees produced for these analyses. Methodology Our focus was to increase the number of bootstrap replications that can be performed on large protein datasets using the maximum parsimony, distance matrix, and maximum likelihood methods. We have modified the PHYLIP package using MPI to enable large-scale phylogenetic study of protein sequences, using a statistically robust number of bootstrapped datasets, to be performed in a moderate amount of time. This paper discusses the methodology used to parallelize the PHYLIP programs and reports the performance of the parallel PHYLIP programs that are relevant to the study of protein evolution on several protein datasets. Conclusions Calculations that currently take a few days on a state of the art desktop workstation are reduced to calculations that can be performed over lunchtime on a modern parallel computer. Of the three protein methods tested, the maximum likelihood method scales the best, followed by the distance method, and then the maximum parsimony method. However, the maximum likelihood method requires significant memory resources, which limits its application to more moderately sized protein datasets.

Ropelewski, Alexander J.; Nicholas, Hugh B.; Gonzalez Mendez, Ricardo R.

2010-01-01

190

A systematic search for linkage with nonsyndromic recessive deafness in two large Middle Eastern inbred kindreds excludes more than 30% of the genome  

SciTech Connect

It has been estimated that as many as 35 loci may individually cause autosomal recessive non-syndromic deafness. The extreme genetic heterogeneity, limited clinical differentiation and phenotypic assortative mating in many western countries make many families unsuitable for genetic linkage studies. Recently the first of those loci was mapped (to 13q) in two consanguineous families from northern Tunisia. We are studying two large highly consanguineous Middle Eastern kindreds (a total of 26 deaf in 98 sampled individuals). Examination in each family showed no evidence of clinical heterogeneity and indicated an uncomplicated profound bilateral sensorineural deafness. We have been able to exclude the 13q locus as the cause of deafness in each kindred and have also excluded such `candidate` loci as regions as those causing Usher`s syndrome type 1 (11q13)(11p), Usher`s syndrome type II (1q32-q41), Waardenburg syndrome type I (2q37), branchio-oto-renal syndrome (8q12-q13), Monge`s deafness (5q31), and Treacher Collins syndrome (5q31.3-q33.3). To date, no lod scores greater than 1 have been obtained in either kindred using 150 RFLT`s, VNTR`s and highly polymorphic microsatellite markers (CA repeats and tetranucleotides). By Morton`s criterion a minimum of 30% of the autosomal genome can be excluded for each kindred separately.

Weiss, S.; Korostishevsky, M. [Sackler Faculty of Medicine, Ramat-Aviv (Israel); Frydman, M. [Haim Sheba Medical Center, Tel-Hashomer (Israel)] [and others

1994-09-01

191

Large plasmids of Escherichia coli and Salmonella encode highly diverse arrays of accessory genes on common replicon families.  

PubMed

Plasmids are important in evolution and adaptation of host bacteria, yet we lack a comprehensive picture of their own natural variation. We used replicon typing and RFLP analysis to assess diversity and distribution of plasmids in the ECOR, SARA, SARB and SARC reference collections of Escherichia coli and Salmonella. Plasmids, especially large (?30 kb) plasmids, are abundant in these collections. Host species and genotype clearly impact plasmid prevalence; plasmids are more abundant in ECOR than SAR, but, within ECOR, subgroup B2 strains have the fewest large plasmids. The majority of large plasmids have unique RFLP patterns, suggesting high variation, even within dominant replicon families IncF and IncI1. We found only four conserved plasmid types within ECOR, none of which are widely distributed. Within SAR, conserved plasmid types are primarily serovar-specific, including a pSLT-like plasmid in 13 Typhimurium strains. Conservation of pSLT contrasts with variability of other plasmids, suggesting evolution of serovar-specific virulence plasmids is distinct from that of most enterobacterial plasmids. We sequenced a conserved serovar Heidelberg plasmid but did not detect virulence or antibiotic resistance genes. Our data illustrate the high degree of natural variation in large plasmids of E. coli and Salmonella, even among plasmids sharing backbone genes. PMID:22939841

Williams, Laura E; Wireman, Joy; Hilliard, Valda C; Summers, Anne O

2012-08-24

192

Lack of evidence for increased genetic loading for autism among families of affected femalesA replication from family history data in two large samples  

Microsoft Academic Search

Both the broad and narrow phenotypes of autism have been consistently observed in family members of affected individuals. Additionally, autism spectrum disorders (ASDs) present four times more often in males than in females, for reasons that are currently unknown. In this study, we examined whether there were differences in familial loading of ASD among families of male versus female probands.

Robin P. Goin-Kochel; Anna Abbacchi; John N. Constantino

2007-01-01

193

Larsen syndrome in two generations of an Italian family.  

PubMed Central

This paper describes a familial case of Larsen syndrome. Typical anomalies were present in the propositus and 2 of his 6 daughters. In addition, all patients had progressive deafness and the 2 daughters had cleft palate. The certain exclusion of any consanguinity between the couple, suggests, in this instance, the dominant mode of transmission of the syndrome. Images

Ventruto, V; Festa, F; Sebastio, L; Sebastio, G

1976-01-01

194

Nonimmune hydrops fetalis in two cases of consanguineous parents and associated with hereditary spherocytosis and hemophagocytic hystiocytosis.  

PubMed

Nonimmune hydrops fetalis may occur as a result of different etiological conditions and in about one-third of cases no cause could be identified. Here, we report two cases of nonimmune hydrops fetalis associated with hereditary spherocytosis and hemophagocytic hystiocytosis. We think that babies with hydrops fetalis born of consanguineous parents should be examined for hereditary diseases, and that these rare causes should be taken into account in problematic cases. PMID:17377610

Yetgin, S; Aytac, S; Gurakan, F; Yurdakok, M

2007-04-01

195

Phenotypic variations in a family with retinal dystrophy as result of different mutations in the ABCRgene  

Microsoft Academic Search

AIMSTo describe two phenotypic variations of autosomal recessive retinal dystrophy occurring in a consanguineous family in a pseudodominant pattern, resulting from mutations in the ATP binding cassette transporter (ABCR) gene.METHODSPatients of this family underwent an extensive ophthalmic evaluation, including fundus photography, fluorescein angiography, and electroretinography (ERG). Genetic analysis comprised sequence analysis of the retina specific ABCR gene.RESULTSFive patients presented with

B Jeroen Klevering; Marc van Driel; Dorien J R van de Pol; Alfred J L G Pinckers; Frans P M Cremers; Carel B Hoyng

1999-01-01

196

Large deletions and splicing-site mutations in the STK11 gene in Peutz-Jeghers Chilean families.  

PubMed

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by mucocutaneous melanocytic macules, gastrointestinal hamartomatous polyposis and an increased risk of various neoplasms. Germline mutations in the serine/threonine kinase 11 (STK11) gene have been identified as a cause for PJS. The aim of this study was to characterize the genotype of Chilean PJS patients. Mutation screening of 13 patients from eight PJS families was performed using a single strand conformation polymorphism analysis, DNA sequencing and multiplex ligation-dependent probe amplification assay. The breakpoints of the genomic rearrangements were assessed by a long-range polymerase chain reaction and sequencing. The results revealed the existence of seven different pathogenic mutations in STK11 gene in seven unrelated families, including three point mutations and four large genomic deletions. Three of these point mutations (43%, 3/7) may be considered as novel. Our results showed that a germline mutation is present in STK11 in 88% of probands fulfilling the diagnostic criteria of PJS. In this study, the combination of two different experimental approaches in the screening of the STK11 in PJS, led to a higher percentage of mutation detection. PMID:22775437

Orellana, P; López-Köstner, F; Heine, C; Suazo, C; Pinto, E; Church, J; Carvallo, P; Alvarez, K

2012-08-07

197

The crystal structure of bacteriophage HK97 gp6: defining a large family of head-tail connector proteins.  

PubMed

The final step in the morphogenesis of long-tailed double-stranded DNA bacteriophages is the joining of the DNA-filled head to the tail. The connector is a specialized structure of the head that serves as the interface for tail attachment and the point of egress for DNA from the head during infection. Here, we report the determination of a 2.1 A crystal structure of gp6 of bacteriophage HK97. Through structural comparisons, functional studies, and bioinformatic analysis, gp6 has been determined to be a component of the connector of phage HK97 that is evolutionarily related to gp15, a well-characterized connector component of bacteriophage SPP1. Whereas the structure of gp15 was solved in a monomeric form, gp6 crystallized as an oligomeric ring with the dimensions expected for a connector protein. Although this ring is composed of 13 subunits, which does not match the symmetry of the connector within the phage, sequence conservation and modeling of this structure into the cryo-electron microscopy density of the SPP1 connector indicate that this oligomeric structure represents the arrangement of gp6 subunits within the mature phage particle. Through sequence searches and genomic position analysis, we determined that gp6 is a member of a large family of connector proteins that are present in long-tailed phages. We have also identified gp7 of HK97 as a homologue of gp16 of phage SPP1, which is the second component of the connector of this phage. These proteins are members of another large protein family involved in connector assembly. PMID:19895817

Cardarelli, Lia; Lam, Robert; Tuite, Ashleigh; Baker, Lindsay A; Sadowski, Paul D; Radford, Devon R; Rubinstein, John L; Battaile, Kevin P; Chirgadze, Nickolay; Maxwell, Karen L; Davidson, Alan R

2009-11-04

198

The Prevalence and Impact of Large Sudden Improvements During Adolescent Therapy for Depression: A Comparison Across Cognitive-Behavioral, Family, and Supportive Therapy  

Microsoft Academic Search

This study assessed the treatment specificity and impact on outcome of large, abrupt symptomatic improvements occurring prior to and during cognitive-behavioral, family, and supportive therapy. Eighty-seven depressed adolescents receiving at least 8 therapy sessions were included. Abrupt large decreases in depressive symptoms were identified by changes in weekly Beck Depression Inventory scores. Overall, 28% experienced a pretreatment gain and 39%

Scott T. Gaynor; V. Robin Weersing; David J. Kolko; Boris Birmaher; Jungeun Heo; David A. Brent

2003-01-01

199

Lack of Evidence for Increased Genetic Loading for Autism among Families of Affected Females: A Replication from Family History Data in Two Large Samples  

ERIC Educational Resources Information Center

Both the broad and narrow phenotypes of autism have been consistently observed in family members of affected individuals. Additionally, autism spectrum disorders (ASDs) present four times more often in males than in females, for reasons that are currently unknown. In this study, we examined whether there were differences in familial loading of ASD…

Goin-Kochel, Robin P.; Abbacchi, Anna; Constantino, John N.

2007-01-01

200

Living in a Large Family Does Something For You: Influence of Family on the Achievement of African and Caribbean Women in Science.  

ERIC Educational Resources Information Center

Examines the influence of the family on women's achievement in scientific careers in the sub-Saharan African and Caribbean regions. Concludes that when compared with their North American and European counterparts, there are significant differences in the family experiences of African and Caribbean women scientists. (Author/SAH)

Beoku-Betts, Josephine A.

2000-01-01

201

Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" ?-galactosidase a large deletion.  

PubMed

Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of ?-galactosidase A (?-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased ?-Gal A activity. However, in female heterozygotes, the ?-Gal A activity can range from low to normal due to random X-chromosomal inactivation, and diagnostic confirmation requires identification of the family's ?-Gal A gene mutation. In a young female who had occasional acroparesthesias, corneal opacities, and 15 to 50% of the lower limit of normal leukocyte ?-Gal A activity, ?-Gal A sequencing in two expert laboratories did not identify a confirmatory mutation, presenting a diagnostic dilemma. A renal biopsy proved diagnostic and renewed efforts to detect an ?-Gal A mutation. Subsequent gene dosage analyses identified a large ?-Gal A deletion confirming her heterozygosity, and she was started on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (>50bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are "sequencing cryptic," resolving molecular diagnostic dilemmas. PMID:21641253

Feldt-Rasmussen, Ulla; Dobrovolny, Robert; Nazarenko, Irina; Ballegaard, Martin; Hasholt, Lis; Rasmussen, Ase K; Christensen, Erik I; Sorensen, Soren S; Wibrand, Flemming; Desnick, Robert J

2011-05-14

202

Molecular and neurological characterizations of three Saudi families with lipoid proteinosis  

PubMed Central

Background Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood. It is caused by homozygous or compound heterozygous mutations in the ECM1 gene. The disease is largely uncharacterized in Arab population and the mutation(s) spectrum in the Arab population is largely unknown. We report the neurologic and neuroradiologic characteristics and ECM1 gene mutations of seven individuals with lipoid proteinosis (LP) from three unrelated consanguineous families. Methods Clinical, neurologic, and neuro-ophthalmologic examinations; skin histopathology; brain CT and MRI; and sequencing of the fullECM1 gene. Results All seven affected individuals had skin scarring and hoarseness from early childhood. The two children in Family 1 had worse skin involvement and worse hoarseness than affected children of Families 2 and 3. Both children in Family 1 were modestly mentally retarded, and one had typical calcifications of the amygdalae on CT scan. Affected individuals in Families 2 and 3 had no grossneurologic, neurodevelopmental, or neuroimaging abnormalities. Skin histopathology was compatible with LP in all three families. Sequencing the full coding region of ECM1 gene revealed two novel mutationsin Family 1 (c.1300-1301delAA) and Family 2 (p.Cys269Tyr) and in Family 3 a previously described 1163 bp deletion starting 34 bp into intron 8. Conclusions These individuals illustrate the neurologic spectrum of LP, including variable mental retardation, personality changes, and mesial temporal calcificationand imply that significant neurologic involvement may be somewhat less common than previously thought. The cause of neurologic abnormalities was not clear from either neuroimaging or from what is known about ECM1 function. The severity of dermatologic abnormalities and hoarseness generally correlated with neurologic abnormalities, with Family 1 being somewhat more affected in all spheres than the other two families. Nevertheless, phenotype-genotype correlation was not obvious, possibly because of difficulty quantifying the neurologic phenotype and because of genetic complexity.

2011-01-01

203

Congenital hypothyroidism: increased incidence in Asian families  

Microsoft Academic Search

Screening in the North West health region of England showed a significantly higher incidence of congenital hypothyroidism in Asian families--1\\/918 compared with 1\\/3391 in non-Asians. This could only in part be explained by consanguinity. No differences were found in birth order, season of birth, gestational age, or birth weight between normal infants and those with congenital hypothyroidism. There was a

M Rosenthal; G M Addison; D A Price

1988-01-01

204

Screening of 38 genes identifies mutations in 62% of families with nonsyndromic deafness in Turkey.  

PubMed

More than 60% of prelingual deafness is genetic in origin, and of these up to 95% are monogenic autosomal recessive traits. Causal mutations have been identified in 1 of 38 different genes in a subset of patients with nonsyndromic autosomal recessive deafness. In this study, we screened 49 unrelated Turkish families with at least three affected children born to consanguineous parents. Probands from all families were negative for mutations in the GJB2 gene, two large deletions in the GJB6 gene, and the 1555A>G substitution in the mitochondrial DNA MTRNR1 gene. Each family was subsequently screened via autozygosity mapping with genomewide single-nucleotide polymorphism arrays. If the phenotype cosegregated with a haplotype flanking one of the 38 genes, mutation analysis of the gene was performed. We identified 22 different autozygous mutations in 11 genes, other than GJB2, in 26 of 49 families, which overall explains deafness in 62% of families. Relative frequencies of genes following GJB2 were MYO15A (9.9%), TMIE (6.6%), TMC1 (6.6%), OTOF (5.0%), CDH23 (3.3%), MYO7A (3.3%), SLC26A4 (1.7%), PCDH15 (1.7%), LRTOMT (1.7%), SERPINB6 (1.7%), and TMPRSS3 (1.7%). Nineteen of 22 mutations are reported for the first time in this study. Unknown rare genes for deafness appear to be present in the remaining 23 families. PMID:21117948

Duman, Duygu; Sirmaci, Asli; Cengiz, F Basak; Ozdag, Hilal; Tekin, Mustafa

2010-11-30

205

Congenital hepatic fibrosis with congenital heart disease. A family study with ultrastructural features of the liver.  

PubMed Central

A family with congenital hepatic fibrosis (CHF) and congenital heart disease (CHD) is presented. The consanguineous healthy parents gave birth to 12 children of whom 10 survived. One son had CHF and CHD, one daughter had CHF and a second daughter had CHD. Three other siblings probably had small a ventricular septal defect and another one probably had mild pulmonary valve stenosis. Development of portal hypertension and hypersplenism necessitated performing shunt operation on both siblings suffering from congenital hepatic fibrosis. Ultrastructural findings were giant mitochondria with large laminar inclusions in hepatocytes, and excess of villi and whorls of membranes and collagen fibrils between hepatocytes. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6

Naveh, Y; Roguin, N; Ludatscher, R; Auslaender, L; Schramek, A; Aharon, M

1980-01-01

206

Using Family-Based Imputation in Genome-Wide Association Studies with Large Complex Pedigrees: The Framingham Heart Study  

PubMed Central

Imputation has been widely used in genome-wide association studies (GWAS) to infer genotypes of un-genotyped variants based on the linkage disequilibrium in external reference panels such as the HapMap and 1000 Genomes. However, imputation has only rarely been performed based on family relationships to infer genotypes of un-genotyped individuals. Using 8998 Framingham Heart Study (FHS) participants genotyped with Affymetrix 550K SNPs, we imputed genotypes of same set of SNPs for additional 3121 participants, most of whom were never genotyped due to lack of DNA sample. Prior to imputation, 122 pedigrees were too large to be handled by the imputation software Merlin. Therefore, we developed a novel pedigree splitting algorithm that can maximize the number of genotyped relatives for imputing each un-genotyped individual, while keeping new sub-pedigrees under a pre-specified size. In GWAS of four phenotypes available in FHS (Alzheimer disease, circulating levels of fibrinogen, high-density lipoprotein cholesterol, and uric acid), we compared results using genotyped individuals only with results using both genotyped and imputed individuals. We studied the impact of applying different imputation quality filtering thresholds on the association results and did not found a universal threshold that always resulted in a more significant p-value for previously identified loci. However most of these loci had a lower p-value when we only included imputed genotypes with with ?60% SNP- and ?50% person-specific imputation certainty. In summary, we developed a novel algorithm for splitting large pedigrees for imputation and found a plausible imputation quality filtering threshold based on FHS. Further examination may be required to generalize this threshold to other studies.

Chen, Wei-Min; Larson, Martin G.; Fox, Caroline S.; Vasan, Ramachandran S.; Seshadri, Sudha; O'Donnell, Christopher J.; Yang, Qiong

2012-01-01

207

Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression.  

PubMed

Patient-specific induced pluripotent stem cells (iPSCs) represent a novel system for modeling human genetic disease and could provide a source of cells for large-scale drug-discovery screens. Here we demonstrate the feasibility of performing a primary screen in neural crest precursors derived from iPSCs that were generated from individuals with familial dysautonomia (FD), a rare, fatal genetic disorder affecting neural crest lineages. We tested 6,912 small-molecule compounds and characterized eight that rescued expression of IKBKAP, the gene responsible for FD. One of the hits, SKF-86466, was found to induce IKBKAP transcription through modulation of intracellular cAMP levels and PKA-dependent CREB phosphorylation. SKF-86466 also rescued IKAP protein expression and the disease-specific loss of autonomic neuronal marker expression. Our data implicate alpha-2 adrenergic receptor activity in regulating IKBKAP expression and demonstrate that small-molecule discovery using an iPSC-based disease model can identify candidate drugs for potential therapeutic intervention. PMID:23159879

Lee, Gabsang; Ramirez, Christina N; Kim, Hyesoo; Zeltner, Nadja; Liu, Becky; Radu, Constantin; Bhinder, Bhavneet; Kim, Yong Jun; Choi, In Young; Mukherjee-Clavin, Bipasha; Djaballah, Hakim; Studer, Lorenz

2012-11-25

208

Characterization and evolutionary analysis of a large polygalacturonase gene family in the oomycete plant pathogen Phytophthora cinnamomi.  

PubMed

Polygalacturonases (PGs) are secreted by fungal pathogens during saprophytic and parasitic growth, and their degradation of pectin in the plant cell wall is believed to play a major role in tissue invasion and maceration. In this study, PG activity was demonstrated in culture filtrates of the oomycete plant pathogen, Phytophthora cinnamomi. A P. cinnamomi pg gene fragment amplified using degenerate primers based on conserved regions in fungal and plant PGs was used to isolate 17 complete P. cinnamomi pg genes and pseudogenes from a genomic library and partial sequence for another two genes. Gel blotting of genomic DNA indicated that there may be even more pg genes in the P. cinnamomi genome. P. cinnamomi pg gene sequences were expressed in PG-deficient yeast and found to confer PG activity, thereby confirming their functional identity. The predicted mature P. cinnamomi PGs fall into subgroups that exhibit large differences in the extent of N-glycosylation, isoelectric points, and N- and C-terminal structure. Evidence for birth-and-death and reticulate evolution in the P. cinnamomi pg gene family was obtained, and some codons for surface exposed residues in the P. cinnamomi PGs were shown to have been subject to diversifying selection. Contrary to accepted phylogenies for other proteins, phylogenetic analysis of the P. cinnamomi PGs revealed a closer relationship with PGs from true fungi than with those from plants. PMID:12236597

Götesson, Arvid; Marshall, Jerry S; Jones, David A; Hardham, Adrienne R

2002-09-01

209

Large Repayments Of Premium Subsidies May Be Owed To The IRS If Family Income Changes Are Not Promptly Reported.  

PubMed

Subsidies for health insurance premiums under the Affordable Care Act are refundable tax credits. They can be taken when taxes are filed or in advance, as reductions in monthly premiums that must be reconciled at tax filing. Recipients who take subsidies in advance will receive tax refunds if their subsidies were too small but will have to make repayments if their subsidies were too high. We analyzed predicted repayments and refunds for people receiving subsidies, using California as a case study. We found that many families could owe large repayments to the Internal Revenue Service at their next tax filing. If income changes were reported and credits adjusted in a timely manner throughout the tax year, the number of filers owing repayments would be reduced by 7-41 percent and the median size of repayments reduced by as much as 61 percent (depending on the level of changes reported and the method used to adjust the subsidy amounts). We recommend that the health insurance exchanges mandated by the Affordable Care Act educate consumers about how the subsidies work and the need to promptly report income changes. We also recommend that they provide tools and assistance to determine the amount of subsidies that enrollees should take in advance. PMID:24019357

Jacobs, Ken; Graham-Squire, Dave; Gould, Elise; Roby, Dylan

2013-09-01

210

Sifting through genomes with iterative-sequence clustering produces a large, phylogenetically diverse protein-family resource  

PubMed Central

Background New computational resources are needed to manage the increasing volume of biological data from genome sequencing projects. One fundamental challenge is the ability to maintain a complete and current catalog of protein diversity. We developed a new approach for the identification of protein families that focuses on the rapid discovery of homologous protein sequences. Results We implemented fully automated and high-throughput procedures to de novo cluster proteins into families based upon global alignment similarity. Our approach employs an iterative clustering strategy in which homologs of known families are sifted out of the search for new families. The resulting reduction in computational complexity enables us to rapidly identify novel protein families found in new genomes and to perform efficient, automated updates that keep pace with genome sequencing. We refer to protein families identified through this approach as “Sifting Families,” or SFams. Our analysis of ~10.5 million protein sequences from 2,928 genomes identified 436,360 SFams, many of which are not represented in other protein family databases. We validated the quality of SFam clustering through statistical as well as network topology–based analyses. Conclusions We describe the rapid identification of SFams and demonstrate how they can be used to annotate genomes and metagenomes. The SFam database catalogs protein-family quality metrics, multiple sequence alignments, hidden Markov models, and phylogenetic trees. Our source code and database are publicly available and will be subject to frequent updates (http://edhar.genomecenter.ucdavis.edu/sifting_families/).

2012-01-01

211

Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families  

Microsoft Academic Search

In communities with high rates of consanguinity and consequently high prevalence of recessive phenotypes, homozygosity mapping with SNP arrays is an effective approach for gene discovery. In 20 Palestinian kindreds with prelingual nonsyndromic hearing loss, we generated homozygosity profiles reflecting linkage to the phenotype. Family sizes ranged from small nuclear families with two affected children, one unaffected sibling, and parents

Hashem Shahin; Tom Walsh; Amal Abu Rayyan; Ming K Lee; Jake Higgins; Diane Dickel; Kristen Lewis; James Thompson; Carl Baker; Alex S Nord; Sunday Stray; David Gurwitz; Karen B Avraham; Mary-Claire King; Moien Kanaan

2010-01-01

212

Mapping of a possible X-linked form of familial developmental dysphasia (FDD) in a single large pedigree  

SciTech Connect

Children diagnosed with developmental dysphasia develop speech very late without exhibiting sensory or motor dysfunction, and when they do begin to speak their grammar is abnormal. A large three-generation British pedigree was recently identified in which 16 out of 30 members were diagnosed as dysphasic. Assuming a dominant mode of inheritance with homogeneous phenotypic expression and complete penetrance among affected members, we showed by simulation analysis that this pedigree has the power to detect linkage to marker loci with an average maximum LOD score of 3.67 at {theta}=0.1. Given the absence of male-to-male transmission and a ratio of female to male affecteds (10/6) in this pedigree within the expected range for an X-linked dominant mode of inheritance, we decided to begin a genome-wide linkage analysis with microsatellite markers on the human X chromosome. Fifteen individuals (10 affected) from three generations were genotyped with 35 polymorphic STS`s (Research Genetics) which were approximately uniformly distributed along the X chromosome. Two-point linkage was assessed using the MLINK and ILINK programs from the LINKAGE package. Markers DXS1223, DXS987, DXS996 and DXS1060 on Xp22 showed consistent linkage to the disease locus with a maximum LOD score of 0.86 at a distance of 22 cM for DXS1060. If further analysis with additional markers and additional family members confirms X-linkage, such a localization would provide support for Lehrke`s hypothesis for X-linkage of major intellectual traits including verbal functioning.

Dunne, P.W.; Doody, R.S.; Epstein, H.F. [Baylor College of Medicine, Houston, TX (United States)] [and others

1994-09-01

213

Application of a sensitive collection heuristic for very large protein families: Evolutionary relationship between adipose triglyceride lipase (ATGL) and classic mammalian lipases  

PubMed Central

Background Manually finding subtle yet statistically significant links to distantly related homologues becomes practically impossible for very populated protein families due to the sheer number of similarity searches to be invoked and analyzed. The unclear evolutionary relationship between classical mammalian lipases and the recently discovered human adipose triglyceride lipase (ATGL; a patatin family member) is an exemplary case for such a problem. Results We describe an unsupervised, sensitive sequence segment collection heuristic suitable for assembling very large protein families. It is based on fan-like expanding, iterative database searches. To prevent inclusion of unrelated hits, additional criteria are introduced: minimal alignment length and overlap with starting sequence segments, finding starting sequences in reciprocal searches, automated filtering for compositional bias and repetitive patterns. This heuristic was implemented as FAMILYSEARCHER in the ANNIE sequence analysis environment and applied to search for protein links between the classical lipase family and the patatin-like group. Conclusion The FAMILYSEARCHER is an efficient tool for tracing distant evolutionary relationships involving large protein families. Although classical lipases and ATGL have no obvious sequence similarity and differ with regard to fold and catalytic mechanism, homology links detected with FAMILYSEARCHER show that they are evolutionarily related. The conserved sequence parts can be narrowed down to an ancestral core module consisting of three ?-strands, one ?-helix and a turn containing the typical nucleophilic serine. Moreover, this ancestral module also appears in numerous enzymes with various substrate specificities, but that critically rely on nucleophilic attack mechanisms.

Schneider, Georg; Neuberger, Georg; Wildpaner, Michael; Tian, Sun; Berezovsky, Igor; Eisenhaber, Frank

2006-01-01

214

Is Psychopathology Part of the Phenotypic Spectrum of Myoclonus-dystonia? A Study of a Large Dutch MD Family  

Microsoft Academic Search

Background: Myoclonus-dystonia (M-D) is a movement disorder frequently caused by mutations in the epsilon-sarcoglycan gene (SGCE, DYT11). In several M-D families, psychiatric symptoms accompanying the motor symptoms have been reported, but I shared genetic etiology remains unclear. Objective: To assess neuropsychologic functioning and psychopathology in DYT11 mutation carriers (MC) and their family members using standardized neuropsychologic and psychiatric measures. Methods:

Elisabeth M. J. Foncke; Danielle Cath; Koos Zwinderman; Jan Smit; Ben Schmand; Marina Tijssen

2009-01-01

215

Large mixing angle MSW and atmospheric neutrinos from single right-handed neutrino dominance and U(1) family symmetry  

Microsoft Academic Search

Single right-handed neutrino dominance (SRHND) in the 23 sector of the light effective neutrino mass matrix has been proposed as a natural explanation for the concurrent large 23 mixing angle and large 23 mass hierarchy. In this paper we show how large 12 mixing angles, suitable for the large mixing angle (LMA) MSW solution to the solar neutrino problem, may

S. F. King

2000-01-01

216

A mutation in CTSK gene in an autosomal recessive pycnodysostosis family of Pakistani origin  

Microsoft Academic Search

BACKGROUND: Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures and skull deformities. Mutations in the gene encoding cathepsin K (CTSK), a lysosomal cysteine protease, have been found to be responsible for this disease. OBJECTIVES: To identify pathogenic mutation in a consanguineous Pakistani family with 3 affected individuals demonstrating autosomal recessive pycnodysostosis. METHODS:

Muhammad Naeem; Sabeen Sheikh; Wasim Ahmad

2009-01-01

217

Mal de Meleda: a report of two cases of familial occurrence.  

PubMed

Mal de Meleda is a rare transgressive palmoplantar keratoderma with an estimated prevalence of 1 in 100,000 individuals. It was first described in 1826 by Stulli on the island of Mljet. Its autosomal recessive inheritance was described in 1938, and the defective gene was localized to chromosome 8 qter in 1998. Clinical features are the result of abnormal palmoplantar keratinization and include severe symmetrical transgressive hyperkeratosis and erythema of the feet and hands in a glove-and-sock pattern. Genetic counseling is mandatory in cases of consanguinity. We report two cases of familial occurrence in the offspring of consanguineous parents. PMID:22068784

Morais e Silva, Fernanda Ayres de; Cunha, Thiago Vinicius Ribeiro da; Boeno, Elisangela dos Santos; Steiner, Denise

218

Mutation in the Tight-Junction Gene Claudin 19 (CLDN19) and Familial Hypomagnesemia, Hypercalciuria, Nephrocalcinosis (FHHNC) and Severe Ocular Disease  

Microsoft Academic Search

Background\\/Aims: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare renal tubular disorder complicated by progressive renal failure during childhood or adolescence. Recently, causative mutations in the CLDN19 gene have been identified in FHHNC patients presenting with severe ocular involvement. The aim of the study was to investigate the molecular genetic defect underlying FHHNC in a consanguineous Pakistani family.

Muhammad Naeem; Sofia Hussain; Naureen Akhtar

2011-01-01

219

Providing maternal and child health-family planning services to a large rural population: results of the Bohol Project, Philippines.  

PubMed

The Bohol Project (1975-1979) sought to improve maternal and child health and to increase the use of family planning among a rural Philippine population of 400,000. Research indicated that maternal and child health (MCH) services did become more available during the Project period and coverage of the priority populations improved. Family planning (FP) use, particularly of less effective methods, increased and fertility declined although some change could have been expected even without the Project. Deaths due to neonatal tetanus were almost eliminated by mortality rates did not decline for a number of reasons, including the fact that services were probably not tailored closely enough to local health problems, especially respiratory diseases. The Project showed that it was possible to increase health and family planning services by using low-cost strategies (such as setting up community drug stores) and by employing paramedical workers, in this case, midwives. Preventive MCH-FP services were not overwhelmed by curative services as had been feared. Perhaps the most significant contributions of the Project were the lessons learned about delivering health and family planning services and conducting evaluation research. In general, if developing countries could maintain well-evaluated field laboratories for working out health and family planning delivery approaches before going nationwide, it is likely that time and money would be saved in the long run. PMID:6848001

Williamson, N E; Parado, J P; Maturan, E G

1983-01-01

220

Identification of multiple loci for Alzheimer disease in a consanguineous Israeli-Arab community  

Microsoft Academic Search

We have observed an unusually high prevalence of dementia of the Alzheimer type (DAT) in Wadi Ara, an inbred Arab community in northern Israel comprising ? 850 persons over the age of 60 years. Family studies revealed that more than one-third of the DAT cases are members of one hamula (tribal group) within Wadi Ara. To map chromosomal loci contributing

Lindsay A. Farrer; Abdalla Bowirrat; Robert P. Friedland; Kristin Waraska; Amos D. Korczyn; Clinton T. Baldwin

2003-01-01

221

Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting  

PubMed Central

Background Although the aetiology of moyamoya disease (MMD) has not been fully clarified, genetic analysis of familial MMD (F?MMD) has considerable potential to disclose it. Objective To determine the inheritance pattern and clinical characteristics of F?MMD to enable precise genetic analyses of the disease. Methods 15 highly aggregated Japanese families (52 patients; 38 women and 14 men) with three or more affected members were examined. The difference in categories of age at onset (child onset, adult onset and asymptomatic) between paternal and maternal transmission was compared by ?2 statistics. Results In all families there had been three or more generations without consanguinity, and all types of transmission, including father?to?son, were observed. Among a total of 135 offspring of affected people, 59 (43.7%) were patients with MMD or obligatory carriers. Affected mothers were more likely to produce late?onset (adult?onset or asymptomatic) female offspring (p?=?0.007). Conclusions The mode of inheritance of F?MMD is autosomal dominant with incomplete penetrance. Thus, in future genetic studies on F?MMD, parametric linkage analyses using large families with an autosomal dominant mode of inheritance are recommended. Genomic imprinting may be associated with the disease.

Mineharu, Y; Takenaka, K; Yamakawa, H; Inoue, K; Ikeda, H; Kikuta, K-I; Takagi, Y; Nozaki, K; Hashimoto, N; Koizumi, A

2006-01-01

222

A report of 8 cases with hemoglobin H disease in an Iranian family.  

PubMed

alpha-Thalassemia is a common genetic disorder in Iran. However, no comprehensive data on epidemiology of severe forms of alpha-thalassemia, including hemoglobin H (HbH) or hydrops fetalis, is available in this population. This is a first case report of an Iranian family with large number of HbH individuals. The proband is a 48-year-old woman, referred to our center with anemia and no history of previous blood transfusions. Similar clinical phenotype has been observed in all of her 5 siblings, 2 of her 4 children, and her granddaughter, whose parents are first cousins. A reverse hybridization assay covering 21 alpha globin mutations was performed to determine the genotype in 11 members of this family and a fetus. HbH genotype was identified in 9 individuals, representing 3 generations, including a fetus. The high prevalence of alpha-thalassemia carriers together with the high rate of consanguineous marriages could lead to a large number of individuals with HbH or even hydrops fetalis in Iranian families. Therefore, to avoid the risk of having affected offspring, carrier detection, genetic counseling, and prenatal diagnosis would be of vital importance for individuals with low red blood cell (RBC) indices, normal iron status, and normal HbA(2) level, who are suspected to be alpha-thalassemia carriers. PMID:20670167

Azarkeivan, Azita; Azita, Azarkeivan; Neishabury, Maryam; Hadavi, Valeh; Esteghamat, Fatemehsadat; Fatemehsadat, Esteghamat; Enrahimkhani, Saideh; Najmabadi, Hossein; Hossein, Najmabadi

2010-08-01

223

Familiality of Tourette Syndrome, Obsessive-Compulsive Disorder, and Attention-Deficit\\Hyperactivity Disorder: Heritability Analysis in a Large Sib-Pair Sample  

PubMed Central

Objective Tourette Syndrome (TS) is a neuropsychiatric disorder with a genetic component that is highly comorbid with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). However, the genetic relationships between these disorders have not been clearly elucidated. In this study we examine the familial relationships between TS, OCD, and ADHD in a large sample of TS families. Method Parent-offspring concordance of TS, OCD, and ADHD was examined in 952 individuals from 222 TS-affected sib pair families originally collected for genetic studies using logistic regression with generalized estimating equations (GEE) to control for correlated data. Variance components methods were used to estimate the heritability and genetic and environmental correlations between TS, OCD, and ADHD. Bilineal families where both parents had either TS or OCD were excluded. Results OCD and ADHD were highly heritable in these TS families. We found significant genetic correlations between TS and OCD and between OCD and ADHD, but not between TS and ADHD. We also found significant environmental correlations between TS and ADHD and between OCD and ADHD. Parental OCD+ADHD was associated with offspring OCD+ADHD. Conclusions This study provides further evidence for a genetic relationship between TS and OCD, and suggests that the observed relationship between TS and ADHD may in part be due to a genetic association between OCD and ADHD and in part due to shared environmental factors.

Mathews, Carol A.; Grados, Marco A.

2010-01-01

224

Clinical variability of the cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy phenotype in two siblings of a large family showing the same mutation  

PubMed Central

A 44-year-old Albanian male was consulted and diagnosed with dementia. His magnetic resonance imaging suggested diffuse white matter changes. The suspicion of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was raised, and a genetic analysis confirmed such a suspicion through uncovering a pathogenic mutation at the level of exon 4 (c.475C>T) of chromosome 19. The patient came from a large family of 13 children, all of whom underwent clinical, genetic, and imaging examination. The pathogenic mutation was found present only in his eldest sister (50 years old), and she presented also very suggestive signs of CADASIL in her respective imaging study, but without any clinically significant counterpart. All other siblings were free from clinical and radiological signs of the disorder. Our opinion was that we were dealing with a mutation showing a very low level of penetrance, with only two siblings affected in a large Albanian family with 13 children.

Vyshka, Gentian; Kruja, Jera

2013-01-01

225

A family of extracytoplasmic proteins that allow transport of large molecules across the outer membranes of gram-negative bacteria.  

PubMed Central

Seventeen fully sequenced and two partially sequenced extracytoplasmic proteins of purple, gram-negative bacteria constitute a homologous family termed the putative membrane fusion protein (MFP) family. Each such protein apparently functions in conjunction with a cytoplasmic membrane transporter of the ATP-binding cassette family, major facilitator superfamily, or heavy metal resistance/nodulation/cell division family to facilitate transport of proteins, peptides, drugs, or carbohydrates across the two membranes of the gram-negative bacterial cell envelope. Evidence suggests that at least some of these transport systems also function in conjunction with a distinct outer membrane protein. We report here that the phylogenies of these proteins correlate with the types of transport systems with which they function as well as with the natures of the substrates transported. Characterization of the MFPs with respect to secondary structure, average hydropathy, and average similarity provides circumstantial evidence as to how they may allow localized fusion of the two gram-negative bacterial cell membranes. The membrane fusion protein of simian virus 5 is shown to exhibit significant sequence similarity to representative bacterial MFPs.

Dinh, T; Paulsen, I T; Saier, M H

1994-01-01

226

Intracellular positioning of isoforms explains an unusually large adenylate kinase gene family in the parasite Trypanosoma brucei  

Microsoft Academic Search

Adenylate kinases occur classically as cytoplasmic and mitochondrial enzymes, but the expression of seven adenylate kinases in the flagellated protozoan parasite Trypanosoma brucei (order, Kinetoplastida; family, Trypanosomatidae) easily exceeds the number of isoforms previously observed within a single cell and raises questions as to their location and function. We show that a requirement to target adenylate kinase into glycosomes, which

Michael L Ginger; E Solange Ngazoa; Claudio A Pereira; Timothy J Pullen; Mostafa Kabiri; Katja Becker; Keith Gull; Dietmar Steverding

2005-01-01

227

Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families.  

PubMed Central

Ataxia with vitamin E deficiency (AVED), or familial isolated vitamin E deficiency, is a rare autosomal recessive neurodegenerative disease characterized clinically by symptoms with often striking resemblance to those of Friedreich ataxia. We recently have demonstrated that AVED is caused by mutations in the gene for alpha-tocopherol transfer protein (alpha-TTP). We now have identified a total of 13 mutations in 27 families. Four mutations were found in >=2 independent families: 744delA, which is the major mutation in North Africa, and 513insTT, 486delT, and R134X, in families of European origin. Compilation of the clinical records of 43 patients with documented mutation in the alpha-TTP gene revealed differences from Friedreich ataxia: cardiomyopathy was found in only 19% of cases, whereas head titubation was found in 28% of cases and dystonia in an additional 13%. This study represents the largest group of patients and mutations reported for this often misdiagnosed disease and points to the need for an early differential diagnosis with Friedreich ataxia, in order to initiate therapeutic and prophylactic vitamin E supplementation before irreversible damage develops.

Cavalier, L; Ouahchi, K; Kayden, H J; Di Donato, S; Reutenauer, L; Mandel, J L; Koenig, M

1998-01-01

228

The Human LARGE Gene from 22q12.3-q13.1 Is a New, Distinct Member of the Glycosyltransferase Gene Family  

Microsoft Academic Search

Meningioma, a tumor of the meninges covering the central nervous system, shows frequent loss of material from human chromosome 22. Homozygous and heterozygous deletions in meningiomas defined a candidate region of >1 Mbp in 22q12.3-q13.1 and directed us to gene cloning in this segment. We characterized a new member of the N-acetylglucosaminyltransferase gene family, the LARGE gene. It occupies >664

Myriam Peyrard; Eyal Seroussi; Ann-Christin Sandberg-Nordqvist; Ya-Gang Xie; Fei-Yu Han; Ingegerd Fransson; John Collins; Ian Dunham; Maria Kost-Alimova; Stephan Imreh; Jan P. Dumanski

1999-01-01

229

Microarray-based analysis of gene expression in very large gene families: the cytochrome P450 gene superfamily of Arabidopsis thaliana  

Microsoft Academic Search

Cytochrome P450 (P450s) are heme-thiolate protein products of a very large gene superfamily, present in all kingdoms and involved in a variety of metabolic reactions. P450s are classified according to the degree of amino acid sequence identity, with P450s of the same family defined as having >40% identity, and P450s of the same subfamily having >55% identity. Currently, 273 P450

Wenying Xu; Søren Bak; Adria Decker; Suzanne M Paquette; René Feyereisen; David W Galbraith

2001-01-01

230

The politics of school choice in two countries with large private?dependent sectors (Spain and Chile): family strategies, collective action and lobbying  

Microsoft Academic Search

In many countries choice of school is an increasing concern for families and governments. In Spain and Chile, it is also associated with a long?standing political cleavage on the regulation of large sectors of private?dependent schools. This article analyses both the micro? and the macro?politics of choice in these two countries, where low?status 15?year?old students record a significant segregation. At

Xavier Rambla; Óscar Valiente; Carla Frías

2011-01-01

231

The fucoxanthin-chlorophyll proteins from a chromophyte alga are part of a large multigene family: structural and evolutionary relationships to other light harvesting antennae  

Microsoft Academic Search

A fucoxanthin-chlorophyll protein (FCP) cDNA from the raphidophyte Heterosigma carterae encodes a 210-amino acid polypeptide that has similarity to other FCPs and to the chlorophyll a\\/b-binding proteins (CABs) of terrestrial plants and green algae. The putative transit sequence has characteristics that resemble\\u000a a signal sequence. The Heterosigma fcp genes are part of a large multigene family which includes members encoding

D. G. Durnford; R. Aebersold; B. R. Green

1996-01-01

232

The fragile X syndrome in a large family. III. Investigations on linkage of flanking DNA markers with the fragile site Xq27  

Microsoft Academic Search

In a large family with the fragile X syndrome, we performed linkage investigations with six probes, detecting RFLPs at both sides of the fragile site Xq27. The nearest flanking markers were cX55.7 (DXS105) on the centromeric side (theta = 0.04, lod 5.0) and St14 (DXS52) on the telomeric side (theta = 0.08, lod 4.0). Non-penetrance could be shown by the

H Veenema; N J Carpenter; E Bakker; M H Hofker; A M Ward; P L Pearson

1987-01-01

233

Plexins Are a Large Family of Receptors for Transmembrane, Secreted, and GPI-Anchored Semaphorins in Vertebrates  

Microsoft Academic Search

In Drosophila, plexin A is a functional receptor for semaphorin-1a. Here we show that the human plexin gene family comprises at least nine members in four subfamilies. Plexin-B1 is a receptor for the transmembrane semaphorin Sema4D (CD100), and plexin-C1 is a receptor for the GPI-anchored semaphorin Sema7A (Sema-K1). Secreted (class 3) semaphorins do not bind directly to plexins, but rather

Luca Tamagnone; Stefania Artigiani; Hang Chen; Zhigang He; Guo-li Ming; Hong-jun Song; Alain Chedotal; Margaret L. Winberg; Corey S. Goodman; Mu-ming Poo; Marc Tessier-Lavigne; Paolo M. Comoglio

1999-01-01

234

Autosomal dominant aplasia cutis congenita: report of a large Italian family and no hint for candidate chromosomal regions  

Microsoft Academic Search

\\u000a Abstract We studied a three-generation pedigree in which seven individuals were affected by aplasia cutis congenita, a rare disorder\\u000a characterized by the congenital absence of the epidermis, dermis and subcutaneous tissue of the vertex or occipital region.\\u000a Accurate clinical and formal genetic analysis suggested that this family was affected by the autosomal dominant form of the\\u000a disease, a hereditary condition

Michele Fimiani; Marco Seri; Pietro Rubegni; Roberto Cusano; Giovambattista De Aloe; Paola Forabosco; Marcella Devoto; Lucio Andreassi; Alessandra Renieri

1999-01-01

235

Age-related Macular Degeneration Clinical Features in a Large Family and Linkage to Chromosome 1q  

Microsoft Academic Search

Methods: An ARMD pedigree was identified, and the disease state of family members was documented by stereoscopic fundus photography and was classified us- ing a modified version of the Wisconsin Age-Related Maculopathy Grading System. A genome-wide screen at approximately 6-centimorgan spacing using a DNA- pooling strategy combined with shared-segment analy- sis was used to identify likely chromosomal regions. The entire

Michael L. Klein; Dennis W. Schultz; Al Edwards; Tara C. Matise; Kristal Rust; C. Blair Berselli; Karmen Trzupek; Richard G. Weleber; Jurg Ott; Mary K. Wirtz; Ted S. Acott; Arch Ophthalmol

1998-01-01

236

Frequency of Familial Colon Cancer and Hereditary Nonpolyposis ColorectalCancer (Lynch Syndrome) in a Large Population Database  

Microsoft Academic Search

Background and aims:\\u000aEstimates have been made concerning the fraction of colorectal cancer (CRC) cases that meet Amsterdam I criteria but not Amsterdam II criteria. The aim of this study was to determine in a population setting what fraction of CRC cases can be considered familial high-risk, what fraction of these meet Amsterdam I or II criteria, and what fraction

Richard A. Kerber; Deborah W. Neklason; Wade S. Samowitz; Randall W. Burt

2005-01-01

237

The hemoglobins of Notothenia angustata, a temperate fish belonging to a family largely endemic to the Antarctic Ocean.  

PubMed

The blood of the teleost Notothenia angustata contains a major hemoglobin (Hb 1, over 95% of the total), accompanied by a minor component (Hb 2). The two hemoglobins have identical beta chains and differ in their alpha chains. The primary structure of both hemoglobins has been established through the elucidation of the complete amino acid sequence of the three chains. The study of the oxygen-binding properties shows that Hb 1 displays the Bohr and Root effects and has high affinity for organic phosphates. N. angustata belongs to the family Nototheniidae, suborder Notothenioidei. Unlike the vast majority of nototheniid species, which live in isolation in the Antarctic Ocean and have developed cold adaptation, N. angustata inhabits the waters of southern New Zealand and is not cold adapted. Although some hematological parameters typically favour oxygen transport in a temperate environment, the hemoglobin multiplicity and structural and functional features closely resemble those of the Antarctic species of the same family and suborder. Thus, N. angustata may be considered as a link between temperate and Antarctic habitats. The hypothetical separation history of N. angustata from the Antarctic species of the same family is discussed in the light of the present findings. PMID:1483479

Fago, A; D'Avino, R; Di Prisco, G

1992-12-15

238

The Sensitivity of Diffuse Large B-Cell Lymphoma Cell Lines to Histone Deacetylase Inhibitor-Induced Apoptosis Is Modulated by BCL-2 Family Protein Activity  

PubMed Central

Background Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease and this variation can often be used to explain the response of individual patients to chemotherapy. One cancer therapeutic approach currently in clinical trials uses histone deacetylase inhibitors (HDACi’s) as monotherapy or in combination with other agents. Methodology/Principal Findings We have used a variety of cell-based and molecular/biochemical assays to show that two pan-HDAC inhibitors, trichostatin A and vorinostat, induce apoptosis in seven of eight human DLBCL cell lines. Consistent with previous reports implicating the BCL-2 family in regulating HDACi-induced apoptosis, ectopic over-expression of anti-apoptotic proteins BCL-2 and BCL-XL or pro-apoptotic protein BIM in these cell lines conferred further resistance or sensitivity, respectively, to HDACi treatment. Additionally, BCL-2 family antgonist ABT-737 increased the sensitivity of several DLBCL cell lines to vorinostat-induced apoptosis, including one cell line (SUDHL6) that is resistant to vorinostat alone. Moreover, two variants of the HDACi-sensitive SUDHL4 cell line that have decreased sensitivity to vorinostat showed up-regulation of BCL-2 family anti-apoptotic proteins such as BCL-XL and MCL-1, as well as decreased sensitivity to ABT-737. These results suggest that the regulation and overall balance of anti- to pro-apoptotic BCL-2 family protein expression is important in defining the sensitivity of DLBCL to HDACi-induced apoptosis. However, the sensitivity of DLBCL cell lines to HDACi treatment does not correlate with expression of any individual BCL-2 family member. Conclusions/Significance These studies indicate that the sensitivity of DLBCL to treatment with HDACi’s is dependent on the complex regulation of BCL-2 family members and that BCL-2 antagonists may enhance the response of a subset of DLBCL patients to HDACi treatment.

Thompson, Ryan C.; Vardinogiannis, Iosif; Gilmore, Thomas D.

2013-01-01

239

A Family-Wide RT-PCR Assay for Detection of Paramyxoviruses and Application to a Large-Scale Surveillance Study  

PubMed Central

Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3? end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals.

van Boheemen, Sander; Bestebroer, Theo M.; Verhagen, Josanne H.; Osterhaus, Albert D. M. E.; Pas, Suzan D.; Herfst, Sander; Fouchier, Ron A. M.

2012-01-01

240

A family-wide RT-PCR assay for detection of paramyxoviruses and application to a large-scale surveillance study.  

PubMed

Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3' end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals. PMID:22496880

van Boheemen, Sander; Bestebroer, Theo M; Verhagen, Josanne H; Osterhaus, Albert D M E; Pas, Suzan D; Herfst, Sander; Fouchier, Ron A M

2012-04-04

241

A random sequencing approach for the analysis of the Trypanosoma cruzi genome: general structure, large gene and repetitive DNA families, and gene discovery.  

PubMed

A random sequence survey of the genome of Trypanosoma cruzi, the agent of Chagas disease, was performed and 11,459 genomic sequences were obtained, resulting in approximately 4.3 Mb of readable sequences or approximately 10% of the parasite haploid genome. The estimated total GC content was 50.9%, with a high representation of A and T di- and trinucleotide repeats. Out of the estimated 5000 parasite genes, 947 putative new genes were identified. Another 1723 sequences corresponded to genes detected previously in T. cruzi through expression sequence tag analysis. 7735 sequences had no matches in the database, but the presence of open reading frames that passed Fickett's test suggests that some might contain coding DNA. The survey was highly redundant, with approximately 35% of the sequences included in a few large sequence families. Some of them code for protein families present in dozens of copies, including proteins essential for parasite survival and retrotransposons. Other sequence families include repetitive DNA present in thousands of copies per haploid genome. Some families in the latter group are new, parasite-specific, repetitive DNAs. These results suggest that T. cruzi could constitute an interesting model to analyze gene and genome evolution due to its plasticity in terms of sequence amplification and divergence. Additional information can be found at http://www.iib.unsam.edu.ar/tcruzi.gss. html. PMID:11116094

Agüero, F; Verdún, R E; Frasch, A C; Sánchez, D O

2000-12-01

242

Further evidence that pediatric-onset bipolar disorder comorbid with ADHD represents a distinct subtype: results from a large controlled family study.  

PubMed

We used familial risk analysis to clarify the diagnostic comorbidity between pediatric BP-I disorder and ADHD, testing the hypothesis that pediatric-BP-I disorder comorbid with ADHD represents a distinct subtype. Structured diagnostic interviews were used to obtain DSM-IV psychiatric diagnoses on first-degree relatives (n = 726) of referred children and adolescents satisfying diagnostic criteria for BP-I disorder (n = 239). For comparison, diagnostic information on the first-degree relatives (N = 511) of non-bipolar ADHD children (N = 162) and the first degree relatives (N = 411) of control children (N = 136) with neither ADHD nor BP-I disorder were examined. BP-I disorder and ADHD in probands bred true irrespective of the comorbidity with the other disorder. We also found that the comorbid condition of BP-I disorder plus ADHD also bred true in families, and the two disorders co-segregated among relatives. This large familial risk analysis provides compelling evidence that pediatric BP-I disorder comorbid with ADHD represents a distinct familial subtype. PMID:22979994

Biederman, Joseph; Faraone, Stephen V; Petty, Carter; Martelon, Marykate; Woodworth, K Yvonne; Wozniak, Janet

2012-09-11

243

Isolation of a gene (DLG3) encoding a second member of the discs-large family on chromosome 17q12-q21  

SciTech Connect

The discs-large family is a collection of proteins that have a common structural organization and are thought to be involved in signal transduction and mediating protein-protein interactions at the cytoplasmic surface of the cell membrane. The defining member of this group of proteins is the gene product of the Drosophila lethal (1) discs large (dlg) 1 locus, which was originally identified by the analysis of recessive lethal mutants. Germline mutations in dlg result in loss of apical-basolateral polarity, disruption of normal cell-cell adhesion, and neoplastic overgrowth of the imaginal disc epithelium. We have isolated and characterized a novel human gene, DLG3, that encodes a new member of the discs-large family of proteins. The putative DLG3 gene product has a molecular weight of 66 kDa and contains a discs-large homologous region, an src oncogene homology motif 3, and a domain with homology to guanylate kinase. The DLG3 gene is located on chromosome 17, in the same segment, 17q12-q21, as the related gene, DLG2. The products of the DLG2 and DLG3 genes show 36% identity and 58% similarity to each other, and both show nearly 60% sequence similarity to p55, an erythroid phosphoprotein that is a component of the red cell membrane. We suggest that p55, DLG2, and DLG3 are closely related members of a gene family, whose protein products have a common structural organization and probably a similar function. 25 refs., 3 figs.

Smith, S.A.; Holik, P.; Stevens, J. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

1996-01-15

244

Attitude of Saudi families affected with hemoglobinopathies towards prenatal screening and abortion and the influence of religious ruling (Fatwa)  

Microsoft Academic Search

Hemoglobinopathies are common inherited disorders in Saudi Arabia. Prenatal diagnosis for such diseases is specific and sensitive but not yet implemented in Saudi Arabia. Saudis are Muslims with a very high rate of consanguinity and inherited genetic disorders. To examine the attitude of Saudi families affected with hemoglobinopathies towards prenatal diagnosis and abortion, and to evaluate the effect of education

Fowzan S. Alkuraya; Ramzi A. Kilani

2001-01-01

245

Evidence for linkage and association between autoimmune thyroid diseases and the 18q12-q21 region in a large Tunisian family.  

PubMed

Many studies have shown linkage between IDDM6 locus on 18q12-q21 chromosome and several autoimmune diseases, suggesting that it might harbour susceptibility genes common to autoimmunity. Using 12 families deriving from a large Tunisian multiplex family (the Akr family) from which 38 people were affected with autoimmune thyroid diseases (AITD), and 193 unrelated AITD patients, tested against 100 healthy subjects, we tried to replicate the positive results previously reported for the IDDM6. Akr members were genotyped with eight microsatellite markers harbouring the IDDM6 region. Multipoint non-parametric linkage analysis have shown a clear peak values of NPL score around D18S41 marker (Z = 3.72, P = 0.0001). Family-based association test (FBAT) and transmission disequilibrium test (TDT) have confirmed linkage results. In particular, a significant association with allele 3 of D18S41 and allele 2 of D18S57 markers was found. Case-control studies, using one intragenic microsatellite (locus CTG18.1) marker in the immunoglobulin transcription factor (ITF2) gene, a 5' flanking AC repeat of the anti-apoptotic BCL-2 gene as well as two SNPs at positions +52 and +1955 from transcription start site of BCL-2, showed no significant association between neither genes and AITD. Our study is the first replication of the 18q12-q21 chromosome region as a potential candidate to AITD genetic susceptibility. The Akr family has shown evidence for linkage between IDDM6 locus and AITD. Moreover, case-control study does not support the involvement of ITF2 and BCL2 genes in AITD pathogenesis. PMID:16426239

Hadj Kacem, H; Rebai, A; Kaffel, N; Abid, M; Ayadi, H

2006-02-01

246

To integrate family planning into the building up of mental civilization by offering comprehensive services.  

PubMed

The government of Nangong City, a newly instituted city with a relatively large proportion of agricultural workers has integrated family planning into the building up of mental civilization. As a result, in 1986, the family planning practice rate was 98.4%. One way the government accomplished this was by developing production to eliminate poverty, to show that population development has a significant impact on socioeconomic development. To help change people's attitudes about family planning, the government 1) used publicity, such as speechmaking, mass media, and courses in population theory; 2) awarded those who made contributions; 3) carried out publicity and education in accordance with characteristics of different groups of people; and 4) encouraged bridegrooms to live with their wives' families if the wives' parents had had no son. Another technique the government used as the popularization of scientific knowledge about population theory, physiology and hygiene, birth control, and eugenics and health in births. A 4th method was to popularize knowledge of laws and regulations, such as of early marriage and consanguineous marriage. 5th, the government developed social security undertakings: 1) giving priority to single-child families and 2) taking care of the elderly. Finally, the government improved maternal and child care by 1) providing premarital health care; 2) creating a project for healthier births and better upbringing; 3) family planning workers showing warm concern for reproductive women; and 4) controlling women's diseases and providing health care knowledge, as well as family planning services. These 6 activities have resulted in 1) the decreasing momentum of per capita arable land being controlled, 2) 1-child couples having more time to learn, 3) the development of educational undertakings, 4) a change in people's traditional practices, and 5) improvement in the understanding of patriotism. PMID:12281754

1988-03-01

247

The Cryphonectria parasitica plasmid pUG1 contains a large ORF with motifs characteristic of family B DNA polymerases.  

PubMed Central

The isolation and characterization of the circular mitochondrial plasmid pUG1 from the ascomycete Cryphonectria parasitica is described. The entire sequence (4182 bp) was obtained and high similarities to DNA-dependent DNA polymerases were revealed. Strikingly common features with the DNA polymerases encoded by the Neurospora intermedia plasmids Fiji and LaBelle, such as matches to the conserved motifs A and B and the presence of TTD instead of DTD in motif C, were found, suggesting the existence of a distinct group of members of the B DNA family polymerases. These strong similarities between the plasmids might suggest a common origin of the C.parasitica and the Neurospora plasmids.

Gobbi, E; Carpanelli, A; Firrao, G; Locci, R

1997-01-01

248

The Cryphonectria parasitica plasmid pUG1 contains a large ORF with motifs characteristic of family B DNA polymerases.  

PubMed

The isolation and characterization of the circular mitochondrial plasmid pUG1 from the ascomycete Cryphonectria parasitica is described. The entire sequence (4182 bp) was obtained and high similarities to DNA-dependent DNA polymerases were revealed. Strikingly common features with the DNA polymerases encoded by the Neurospora intermedia plasmids Fiji and LaBelle, such as matches to the conserved motifs A and B and the presence of TTD instead of DTD in motif C, were found, suggesting the existence of a distinct group of members of the B DNA family polymerases. These strong similarities between the plasmids might suggest a common origin of the C.parasitica and the Neurospora plasmids. PMID:9241241

Gobbi, E; Carpanelli, A; Firrao, G; Locci, R

1997-08-15

249

Family caregiving and emotional strain: associations with quality of life in a large national sample of middle-aged and older adults  

Microsoft Academic Search

Purpose  This study examined the quality of life correlates of family caregiving and caregiving strain in a large national epidemiological\\u000a sample.\\u000a \\u000a \\u000a \\u000a Methods  Structured telephone interviews were conducted with 43,099 participants as part of the REasons for Geographic and Racial Differences\\u000a in Stroke (REGARDS) study. Participants completed the 12-item short form health survey (SF-12) and brief measures of depressive\\u000a symptoms, social contacts, and

David L. Roth; Virginia G. Wadley; Ella M. Temple; William E. Haley

2009-01-01

250

Consanguinity around the world: what do the genomic data of the HGDP-CEPH diversity panel tell us?  

PubMed Central

Inbreeding coefficients and consanguineous mating types are usually inferred from population surveys or pedigree studies. Here, we present a method to estimate them from dense genome-wide single-nucleotide polymorphism genotypes and apply it to 940 unrelated individuals from the Human Genome Diversity Panel (HGDP-CEPH). Inbreeding is observed in almost all populations of the panel, and the highest inbreeding levels and frequencies of inbred individuals are found in populations of the Middle East, Central South Asia and the Americas. In these regions, first cousin (1C) marriages are the most frequent, but we also observed marriages between double first cousins (2 × 1C) and between avuncular (AV) pairs. Interestingly, if 2 × 1C marriages are preferred to AV marriages in Central South Asia and the Middle East, the contrary is found in the Americas. There are thus some regional trends but there are also some important differences between populations within a region. Individual results can be found on the CEPH website at ftp://ftp.cephb.fr/hgdp_hbd/.

Leutenegger, Anne-Louise; Sahbatou, Mourad; Gazal, Steven; Cann, Howard; Genin, Emmanuelle

2011-01-01

251

Large-Scale Purification and Characterization of Barley Limit Dextrinase, a Member of the ?-Amylase Structural Family  

Microsoft Academic Search

Cereal Chem. 75(4):473-479 Homogeneous barley limit dextrinase (LD) was isolated on a large scale in a yield of 9 mg\\/kg of 10-day germinated green malt. This represents a 9,400-fold purification and 29% recovery of the activity in a flour extract in 0.2M NaOAc (pH 5.0) containing 5 mM ascorbic acid. The purifica- tion protocol consists of precipitation from the extract

Michael Kristensen; Véronique Planchot; Jun-ichi Abe; Birte Svensson

1998-01-01

252

Identification of a novel BRCA1 large genomic rearrangement in a Spanish breast\\/ovarian cancer family  

Microsoft Academic Search

Background Alterations in BRCA1 gene are responsible for the majority of hereditary breast and\\/or ovarian cancers. However, the frequency of detected germline\\u000a mutations is lower than expected by linkage analysis. Standard PCR-based screening methods are mainly used for detecting mutations,\\u000a but the large genomic rearrangements are commonly overlooked. The purpose of this study was to confirm and characterize a\\u000a novel

Sarai Palanca Suela; Eva Esteban Cardeñosa; Eva Barragán González; Silvestre Oltra Soler; Inma de Juan Jiménez; Isabel Chirivella González; Ángel Segura Huerta; Carmen Guillén Ponce; Eduardo Martínez de Dueñas; Pascual Bolufer Gilabert

2008-01-01

253

Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene  

PubMed Central

Background Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance. Methods Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the EVC/EVC2 locus. The results did not exclude linkage, so samples were sequenced for mutations. Results We identified a c.1868T>C mutation in EVC, which predicts p.L623P, and was homozygous in affected individuals. Conclusion We conclude that this EVC mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. EVC mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.

Ulucan, Hakan; Gul, Davut; Sapp, Julie C; Cockerham, John; Johnston, Jennifer J; Biesecker, Leslie G

2008-01-01

254

A Random Sequencing Approach for the Analysis of the Trypanosoma cruzi Genome: General Structure, Large Gene and Repetitive DNA Families, and Gene Discovery  

PubMed Central

A random sequence survey of the genome of Trypanosoma cruzi, the agent of Chagas disease, was performed and 11,459 genomic sequences were obtained, resulting in ?4.3 Mb of readable sequences or ?10% of the parasite haploid genome. The estimated total GC content was 50.9%, with a high representation of A and T di- and trinucleotide repeats. Out of the estimated 5000 parasite genes, 947 putative new genes were identified. Another 1723 sequences corresponded to genes detected previously in T. cruzi through expression sequence tag analysis. 7735 sequences had no matches in the database, but the presence of open reading frames that passed Fickett's test suggests that some might contain coding DNA. The survey was highly redundant, with ?35% of the sequences included in a few large sequence families. Some of them code for protein families present in dozens of copies, including proteins essential for parasite survival and retrotransposons. Other sequence families include repetitive DNA present in thousands of copies per haploid genome. Some families in the latter group are new, parasite-specific, repetitive DNAs. These results suggest that T. cruzi could constitute an interesting model to analyze gene and genome evolution due to its plasticity in terms of sequence amplification and divergence. Additional information can be found at http://www.iib.unsam.edu.ar/tcruzi.gss.html. [The sequence data described in this paper have been submitted to the dbGSS database under the following GenBank accession nos.: AQ443439–AQ443513, AQ443743–AQ445667, AQ902981–AQ911366, AZ049857–AZ051184, and AZ302116–AZ302563.

Aguero, Fernan; Verdun, Ramiro E.; Frasch, Alberto Carlos C.; Sanchez, Daniel O.

2000-01-01

255

NLRP3 E311K mutation in a large family with Muckle-Wells syndrome - description of a heterogeneous phenotype and response to treatment  

PubMed Central

Introduction Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease characterized by fever, rash, arthralgia, conjunctivitis, sensorineural deafness and potentially life-threatening amyloidosis. The NLRP3/CIAS1 E311K mutation caused a heterogeneous phenotype of MWS in a large family. This study analyzes the clinical spectrum, patterns of inflammatory parameters and reports on response to treatment. Methods A total of 42 patients and family members were screened for the presence of the NLRP3 mutation. Clinical symptoms were reviewed in all family members. Classical (erythrocyte sedimentation rate (ESR, C-reactive protein (CRP)) and novel MWS inflammatory markers (serum amyloid A (SAA), cytokines, cytokine receptor levels) were determined. Patients were treated with the IL-1 inhibitors Anakinra or Canakinumab. Results All 13 clinically affected patients were heterozygous carriers of the amino acid substitution p.Glu311Lys/E311K encoded by exon 3 of the NLRP3 gene, but none of the healthy family members. Disease manifestations varied widely. Except for one child, all carriers suffered from hearing loss and severe fatigue. TNF-?, IL-6, TNF-RI, and TNF-RII levels as well as SAA were elevated in three, two, one, six and ten patients, respectively. Both clinical and laboratory parameters responded quickly and sustainedly to treatment with Anakinra or Canakinumab. Conclusion The NLRP3 E311K mutation is associated with a heterogeneous clinical spectrum, which may expand the view on MWS presentation. The leading symptom was hearing loss. Pericarditis, a rare but severe clinical feature of MWS, was diagnosed in three patients. One patient had a severe course, which led to renal failure secondary to amyloidosis. IL-1 inhibition leads to rapid and sustained improvement of symptoms.

2011-01-01

256

Precise localization of genes on large animal virus genomes: use of lambda gt11 and monoclonal antibodies to map the gene for a cytomegalovirus protein family.  

PubMed Central

We describe an efficient procedure, which uses monoclonal antibodies directed against specific viral proteins, for the precise mapping of genes on large DNA virus genomes. We have used the technique to locate the gene encoding a family of antigenically related DNA-binding proteins on the 240-kilobase-pair human cytomegalovirus (CMV) genome. A random library of CMV DNA fragments was generated using the prokaryotic vector lambda gt11, which expresses open reading frames as beta-galactosidase fusion proteins in infected Escherichia coli. The library was screened with a mixture of monoclonal antibodies directed against the gene products of interest. The coding sequence for infected cell protein 36 (ICP36) was localized to a 2800-base-pair EcoRI fragment (map coordinates 0.228-0.240) on the CMV(Towne) and CMV(AD169) genomes by using DNA from immunoreactive lambda gt11 as probe. A 5000-nucleotide transcript from this region was detected during the early and late phases of the CMV growth cycle. This transcript directed the synthesis of the predominant member of the ICP36 family when hybrid-selected and translated in vitro. Immunoprecipitation of the in vitro translation product with the same monoclonal antibodies used in the initial mapping confirmed the location of the ICP36 gene. These studies establish the utility of the lambda gt11 expression system for rapid and precise mapping of CMV genes (or other large animal virus genes) that encode proteins for which serological reagents exist. Images

Mocarski, E S; Pereira, L; Michael, N

1985-01-01

257

Molecular Analysis of a Large Subtelomeric Nucleotide-Binding-Site-Leucine-Rich-Repeat Family in Two Representative Genotypes of the Major Gene Pools of Phaseolus vulgaris  

PubMed Central

In common bean, the B4 disease resistance (R) gene cluster is a complex cluster localized at the end of linkage group (LG) B4, containing at least three R specificities to the fungus Colletotrichum lindemuthianum. To investigate the evolution of this R cluster since the divergence of Andean and Mesoamerican gene pools, DNA sequences were characterized from two representative genotypes of the two major gene pools of common bean (BAT93: Mesoamerican; JaloEEP558: Andean). Sequences encoding 29 B4-CC nucleotide-binding-site–leucine-rich-repeat (B4-CNL) genes were determined—12 from JaloEEP558 and 17 from BAT93. Although sequence exchange events were identified, phylogenetic analyses revealed that they were not frequent enough to lead to homogenization of B4-CNL sequences within a haplotype. Genetic mapping based on pulsed-field gel electrophoresis separation confirmed that the B4-CNL family is a large family specific to one end of LG B4 and is present at two distinct blocks separated by 26 cM. Fluorescent in situ hybridization on meiotic pachytene chromosomes revealed that two B4-CNL blocks are located in the subtelomeric region of the short arm of chromosome 4 on both sides of a heterochromatic block (knob), suggesting that this peculiar genomic environment may favor the proliferation of a large R gene cluster.

Geffroy, Valerie; Macadre, Catherine; David, Perrine; Pedrosa-Harand, Andrea; Sevignac, Mireille; Dauga, Catherine; Langin, Thierry

2009-01-01

258

Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study.  

PubMed

Genetic association studies of SLC6A4 (SERT) and obsessive-compulsive disorder (OCD) have been equivocal. We genotyped 1241 individuals in 278 pedigrees from the OCD Collaborative Genetics Study for 13 single-nucleotide polymorphisms, for the linked polymorphic region (LPR) indel with molecular haplotypes at rs25531, for VNTR polymorphisms in introns 2 and 7 and for a 381-bp deletion 3' to the LPR. We analyzed using the Family-Based Association Test (FBAT) under additive, dominant, recessive and genotypic models, using both OCD and sex-stratified OCD as phenotypes. Two-point FBAT analysis detected association between Int2 (P = 0.0089) and Int7 (P = 0.0187) (genotypic model). Sex-stratified two-point analysis showed strong association in females with Int2 (P<0.0002), significant after correction for linkage disequilibrium, and multiple marker and model testing (P(Adj) = 0.0069). The SLC6A4 gene is composed of two haplotype blocks (our data and the HapMap); FBAT whole-marker analysis conducted using this structure was not significant. Several noteworthy nonsignificant results have emerged. Unlike Hu et al., we found no evidence for overtransmission of the LPR L(A) allele (genotype relative risk = 1.11, 95% confidence interval: 0.77-1.60); however, rare individual haplotypes containing L(A) with P<0.05 were observed. Similarly, three individuals (two with OCD/OCPD) carried the rare I425V SLC6A4 variant, but none of them passed it on to their six OCD-affected offspring, suggesting that it is unlikely to be solely responsible for the 'OCD plus syndrome', as reported by Ozaki et al. In conclusion, we found evidence of genetic association at the SLC6A4 locus with OCD. A noteworthy lack of association at the LPR, LPR-rs25531 and rare 425V variants suggests that hypotheses about OCD risk need revision to accommodate these new findings, including a possible gender effect. PMID:19806148

Voyiaziakis, E; Evgrafov, O; Li, D; Yoon, H-J; Tabares, P; Samuels, J; Wang, Y; Riddle, M A; Grados, M A; Bienvenu, O J; Shugart, Y Y; Liang, K-Y; Greenberg, B D; Rasmussen, S A; Murphy, D L; Wendland, J R; McCracken, J T; Piacentini, J; Rauch, S L; Pauls, D L; Nestadt, G; Fyer, A J; Knowles, J A

2009-10-06

259

Direct repeats located within a large family of human endogenous retroviral LTRs have transcriptional suppressor activity in human cells  

SciTech Connect

The human genome harbors thousands of sequences that resemble retroviral long terminal repeats (LTRs). These LTR-like elements are associated with full length endogenous retroviral sequences and can also be found as solitary units. Since the U3 regions of retroviral LTRs contain transcriptional regulatory sequences, we have been interested in determining how the presence of endogenous LTRs may affect adjacent gene expression. One endogenous retroviral family, termed HERV-H, has {approximately}1000 copies per haploid genome in addition to {approximately}1000 solitary LTRs. HERV-H LTRs can be grouped into 3 subtypes that vary greatly in their promoter and enhancer activity. The primary feature that distinguishes the 3 LTR subtypes is the sequence of direct repeats located in U3. The most numerous LTR subtype, type 1, has 2 copies of a 47 bp repeat while the next most abundant type, type 2, usually has 5 copies of a different 31 bp repeat. The transcriptional activity of both type 1 and 2 LTRs is limited compared to the activity of a less abundant third subtype, type 1a, which is a much stronger promoter. Type 1a LTRs appear to be a recombinant between types 1 and 2, having only a single type 1 and a single type 2 repeat. In this study, we have analyzed type 1 and 2 repeats for enhancer or suppressor function. Using transient expression of a reporter gene, we have found that a set of type 2 repeats suppresses activity of a type 1a LTR promoter and the human {beta}-globulin promoter. Two sets of the type 1 repeat also have a suppressor effect. Thus, it is possible that type 1 and 2 LTRs in the genome could suppress the expression of nearby genes. Interestingly, HERV-H elements with type 1a LTRs appeared most recently in evolution, being restricted to the great apes and humans. These results suggest that disruption of the repeat structure in type 1a LTRs may be at least partially responsible for their strong promoter activity and their resultant genomic expansion.

Nelson, D.T.; Mager, D.L. [Univ. of British Columbia, Vancouver (Canada)

1994-09-01

260

A Large Family with Carney Complex Caused by the S147G PRKAR1A Mutation Shows a Unique Spectrum of Disease Including Adrenocortical Cancer  

PubMed Central

Context: Most tumors in Carney complex (CNC) are benign, including primary pigmented nodular adrenocortical disease (PPNAD), the main endocrine tumor in CNC. Adrenocortical cancer (AC) has never been observed in the syndrome. Herein, we describe a large Azorean family with CNC caused by a point mutation in the PRKAR1A gene coding for type 1-? (RI?) regulatory subunit of the cAMP-dependent protein kinase A, in which the index patient presented with AC. Objective: We studied the genotype-phenotype correlation in CNC. Design and Setting: We reported on case series and in vitro testing of the PRKAR1A mutation in a tertiary care referral center. Patients: Twenty-two members of a family were investigated for Cushing syndrome and other CNC components; their DNA was sequenced for PRKAR1A mutations. Results: Cushing syndrome due to PPNAD occurred in four patients, including the proposita who presented with AC and three who had Cushing syndrome and/or PPNAD. Lentigines were found in six additional patients who did not have PPNAD. A base substitution (c.439A>G/p.S147G) in PRKAR1A was identified in the proposita, in the three others with PPNAD, in the proposita's twin daughters who had lentigines but no evidence of hypercortisolism, and in five other family members, including one without lentigines or evidence of hypercortisolism. Unlike in other RI? defects, loss of heterozygosity was not observed in AC. The S147G mutation was compared to other expressed PRKAR1A mutations; it led to decreased cAMP and catalytic subunit binding by RI? and increased protein kinase A activity in vitro. Conclusions: In a large family with CNC, one amino acid substitution caused a spectrum of adrenal disease that ranged from lack of manifestations to cancer. PPNAD and AC were the only manifestations of CNC in these patients, in addition to lentigines. These data have implications for counseling patients with CNC and are significant in documenting the first case of AC in the context of PPNAD.

Anselmo, Joao; Medeiros, Sandra; Carneiro, Victor; Greene, Elizabeth; Levy, Isaac; Nesterova, Maria; Lyssikatos, Charalampos; Horvath, Anelia; Carney, J. Aidan

2012-01-01

261

Nucleotide sequence analysis of the large (L) genomic RNA segment of Bunyamwera virus, the prototype of the family Bunyaviridae.  

PubMed

The complete nucleotide sequence of the large (L) genome segment of Bunyamwera virus has been determined from overlapping cDNA clones. The segment is 6875 nucleotides long and has a base composition of 29.8% A, 17.9% C, 15.4% G, and 36.9% U. Eighteen of the terminal 19 nucleotides at the 3' and 5' ends are complementary. In the viral-complementary (+ sense) RNA there is a single long open reading frame (ORF) from AUG at bases 51-53 to a UAG stop codon at bases 6765-6767; this ORF encodes a polypeptide of 2238 amino acids (MW 259,000), corresponding to the L protein which has been mapped to the L RNA segment by analysis of reassortants of Bunyamwera, Batai, and Maguari viruses. The amino-terminal 46 amino acids of the L protein show strong homology (63% identity) with the amino-termini of ORFs predicted from limited sequence analysis of the L segments of La Crosse and snowshoe hare bunyaviruses. Comparison with the polymerase proteins encoded by other negative-strand viruses showed weak homology with part of the influenza virus PB1 protein, but no homology was detected with the other influenza virus polymerase proteins nor with the L proteins of arenaviruses, paramyxoviruses, and rhabdoviruses. At the 5' end of genomic (- sense) RNA there is an AUG-initiated ORF potentially encoding a protein of 14,700; the significance of this ORF is unknown at present. PMID:2596023

Elliott, R M

1989-12-01

262

Assimilation of Consanguineous Mafic Intrutions: Layered Crustal Sill Complexes as Reactive Filters for Continental Basalts  

NASA Astrophysics Data System (ADS)

Continental basalts commonly display variations in their chemical compositions that are inferred to reflect fractionational crystallization (FC), recharge-FC (RFC), assimilation-FC (AFC), or recharge-AFC (RAFC). The dominance of AFC-related processes reflects the intrinsic linkage between crystallization (which releases latent heat) and assimilation (which consumes latent heat). One of the central questions in any assimilation process, however, is what exactly is being assimilated. It is commonly assumed in most AFC models for the intrusion of basalt into continental crust that the contaminant is pre-existing continental crust - that is, felsic gneiss of roughly granodioritic to tonalitic composition, which is enriched in K2O and other large ion lithophiles relative to mantle-derived basalts. These continental gneisses are commonly Precambrian in age and are enriched in the lithophilic isotope ratios 87Sr/86Sr, 207Pb/204Pb, and 208Pb/204Pb, and depleted in 143Nd/144Nd. As a result, AFC-related processes involving this ancient continental crust component typically result in basaltic lavas that are enriched in LILE (e.g., K) relative to high-field strength elements (e.g., Ti, P) and enriched in the heavy isotopes of Sr, Pb, and Nd compared to the primary or parental magma. Contrary to these expectations, basalts of the Snake River volcanic province that display chemical variations diagnostic of AFC (e.g., increasing La/Lu with decreasing mg#) are commonly characterized by essentially constant isotopic ratios of Sr, Pb and Nd, and by LILE/HFSE ratios (e.g., K/P) that decrease with decreasing mg#. We propose that these basalts assimilated a ferrogabbro derived from a parent magma that was the same or similar to the magmas being intruded to recharge the system. Melts derived from this ferrogabbro would be low in K and enriched in Fe, Ti, P, and La/Lu relative to the primitive recharge magma; the isotopic composition would be the same as the primitive recharge magma. We infer that this exchange took place within a 10 km thick mafic sill complex that has been imaged seismically at depths of 12-22 km the middle crust. We propose that this process may apply to a wide range of continental basalts.

Shervais, J. W.; Hanan, B. B.; Vetter, S. K.

2007-12-01

263

Congenital muscular dystrophy associated with calf hypertrophy, microcephaly and severe mental retardation in three Italian families: evidence for a novel CMD syndrome  

Microsoft Academic Search

We describe four Italian patients (aged 3, 4, 12, and 13 years ) affected by a novel autosomal form of recessive congenital muscular dystrophy. These patients were from three non-consanguineous families and presented an almost identical phenotype. This was characterized by hypotonia at birth, joint contractures associated with severe psychomotor retardation, absent speech, inability to walk and almost no interest

Marcello Villanova; Eugenio Mercuri; Enrico Bertini; Patrizia Sabatelli; Lucia Morandi; Marina Mora; Caroline Sewry; Martin Brockington; Susan C Brown; Ana Ferreiro; Nadir M Maraldi; Tatsushi Toda; Pascale Guicheney; Luciano Merlini; Francesco Muntoni

2000-01-01

264

Characterization of a novel missense mutation in the prodomain of GDF5, which underlies brachydactyly type C and mild Grebe type chondrodysplasia in a large Pakistani family.  

PubMed

All TGF-beta family members have a prodomain that is important for secretion. Lack of secretion of a TGF-beta family member GDF5 is known to underlie some skeletal abnormalities, such as brachydactyly type C that is characterized by a huge and unexplained phenotypic variability. To search for potential phenotypic modifiers regulating secretion of GDF5, we compared cells overexpressing wild type (Wt) GDF5 and GDF5 with a novel mutation in the prodomain identified in a large Pakistani family with Brachydactyly type C and mild Grebe type chondrodyslplasia (c527T>C; p.Leu176Pro). Initial in vitro expression studies revealed that the p.Leu176Pro mutant (Mut) GDF5 was not secreted outside the cells. We subsequently showed that GDF5 was capable of forming a complex with latent transforming growth factor binding proteins, LTBP1 and LTBP2. Furthermore, secretion of LTBP1 and LTBP2 was severely impaired in cells expressing the Mut-GDF5 compared to Wt-GDF5. Finally, we demonstrated that secretion of Wt-GDF5 was inhibited by the Mut-GDF5, but only when LTBP (LTBP1 or LTBP2) was co-expressed. Based on these findings, we suggest a novel model, where the dosage of secretory co-factors or stabilizing proteins like LTBP1 and LTBP2 in the microenvironment may affect the extent of GDF5 secretion and thereby function as modifiers in phenotypes caused by GDF5 mutations. PMID:23812741

Farooq, Muhammad; Nakai, Hiroyuki; Fujimoto, Atsushi; Fujikawa, Hiroki; Kjaer, Klaus Wilbrandt; Baig, Shahid Mahmood; Shimomura, Yutaka

2013-06-29

265

The fragile X syndrome in a large family. III. Investigations on linkage of flanking DNA markers with the fragile site Xq27.  

PubMed Central

In a large family with the fragile X syndrome, we performed linkage investigations with six probes, detecting RFLPs at both sides of the fragile site Xq27. The nearest flanking markers were cX55.7 (DXS105) on the centromeric side (theta = 0.04, lod 5.0) and St14 (DXS52) on the telomeric side (theta = 0.08, lod 4.0). Non-penetrance could be shown by the presence of the grandpaternal X chromosome in three mentally retarded fra(X) positive males. A second non-penetrant male in this family had inherited an abnormal grandmaternal X chromosome. His carrier mother had two retarded fra(X) positive brothers. Intermediate between the non-penetrant and fully penetrant males was a non-retarded male, who expressed the fragile site in 6% of his cells. His X chromosome showed the same polymorphisms as were found in his seven severely retarded brothers. In five fra(X) negative females the presence of an abnormal X chromosome could be demonstrated. Despite the existence of non-penetrance in this pedigree, there was no close linkage between a factor IX polymorphism and the fragile site (theta = 0.16, lod 1.9). However, in six descendants of a non-penetrant male, the change to penetrance appeared to be accompanied by a low recombination frequency for flanking markers.

Veenema, H; Carpenter, N J; Bakker, E; Hofker, M H; Ward, A M; Pearson, P L

1987-01-01

266

Absence of linkage of phonological coding dyslexia to chromosome 6p23-p21.3 in a large family data set.  

PubMed Central

Previous studies have suggested that a locus predisposing to specific reading disability (dyslexia) resides on chromosome 6p23-p21.3. We investigated 79 families having at least two siblings affected with phonological coding dyslexia, the most common form of reading disability (617 people genotyped, 294 affected), and we tested for linkage with the genetic markers reported to be linked to dyslexia in those studies. No evidence for linkage was found by LOD score analysis or affected-sib-pair methods. However, using the affected-pedigree-member (APM) method, we detected significant evidence for linkage and/or association with some markers when we used published allele frequencies with weighting of rarer alleles. APM results were not significant when we used marker allele frequencies estimated from parents. Furthermore, results were not significant with the more robust SIMIBD method using either published or parental marker frequencies. Finally, family-based association analysis using the AFBAC program showed no evidence for association with any marker. We conclude that the APM method should be used only with extreme caution, because it appears to have generated false-positive results. In summary, using a large data set with high power to detect linkage, we were unable to find evidence for linkage or association between phonological coding dyslexia and chromosome 6p markers.

Field, L L; Kaplan, B J

1998-01-01

267

Making the alternative the mainstream. Maintaining a family-centered focus in a large freestanding birth center for low-income women.  

PubMed

The BirthPlace program in San Diego, California, is an example of a successfully "mainstreamed" alternative maternity care program. It was developed to address an access to prenatal care problem in the county, and it has successfully integrated four systems of care: 1) a private practice of nurse-midwives and obstetricians, 2) the public community clinic system, 3) the tertiary university hospital, and 4) a freestanding birth center. It provides a model of care that, if replicated, could be an answer for ensuring universal access to maternity care in the United States. The BirthPlace program primarily serves a public-funded, Hispanic population, with certified nurse-midwives as the primary providers. The program's greatest challenge has been to maintain a personalized, family-centered focus, which has been the hallmark of freestanding birth centers to date, in the face of large numbers of clients and low reimbursement for care. The program has addressed the challenge of increasing access and cost-effectiveness while ensuring family-centered care through decentralized clinic management, informed consent, culturally sensitive care, and appropriate use of technology. However, in the face of an ever-changing health care system, balancing these issues will remain a constant challenge as we reshape our maternity care services. PMID:8027847

Dickinson, C P; Jackson, D J; Swartz, W H

268

Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage.  

PubMed

The aim of this study was to estimate the heritability of and environmental contributions to skeletal muscle phenotypes (appendicular lean mass and calf muscle cross-sectional area) in subjects of African descent and to determine whether heritability estimates are impacted by sex or age. Body composition was measured by dual-energy X-ray absorptiometry and computed tomography in 444 men and women aged 18 yr and older (mean: 43 yr) from eight large, multigenerational Afro-Caribbean families (family size range: 21-112). Using quantitative genetic methods, we estimated heritability and the association of anthropometric, lifestyle, and medical variables with skeletal muscle phenotypes. In the overall group, we estimated the heritability of lean mass and calf muscle cross-sectional area (h(2) = 0.18-0.23, P < 0.01) and contribution of environmental factors to these phenotypes (r(2) = 0.27-0.55, P < 0.05). In our age-specific analysis, the heritability of leg lean mass was lower in older vs. younger individuals (h(2) = 0.05 vs. 0.23, respectively, P = 0.1). Sex was a significant covariate in our models (P < 0.001), although sex-specific differences in heritability varied depending on the lean mass phenotype analyzed. High genetic correlations (rho(G) = 0.69-0.81; P < 0.01) between different lean mass measures suggest these traits share a large proportion of genetic components. Our results demonstrate the heritability of skeletal muscle traits in individuals of African heritage and that heritability may differ as a function of sex and age. As the loss of skeletal muscle mass is related to metabolic abnormalities, disability, and mortality in older individuals, further research is warranted to identify specific genetic loci that contribute to these traits in general and in a sex- and age-specific manner. PMID:17656630

Prior, Steven J; Roth, Stephen M; Wang, Xiaojing; Kammerer, Candace; Miljkovic-Gacic, Iva; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

2007-07-26

269

ProfileGrids as a new visual representation of large multiple sequence alignments: a case study of the RecA protein family  

PubMed Central

Background Multiple sequence alignments are a fundamental tool for the comparative analysis of proteins and nucleic acids. However, large data sets are no longer manageable for visualization and investigation using the traditional stacked sequence alignment representation. Results We introduce ProfileGrids that represent a multiple sequence alignment as a matrix color-coded according to the residue frequency occurring at each column position. JProfileGrid is a Java application for computing and analyzing ProfileGrids. A dynamic interaction with the alignment information is achieved by changing the ProfileGrid color scheme, by extracting sequence subsets at selected residues of interest, and by relating alignment information to residue physical properties. Conserved family motifs can be identified by the overlay of similarity plot calculations on a ProfileGrid. Figures suitable for publication can be generated from the saved spreadsheet output of the colored matrices as well as by the export of conservation information for use in the PyMOL molecular visualization program. We demonstrate the utility of ProfileGrids on 300 bacterial homologs of the RecA family – a universally conserved protein involved in DNA recombination and repair. Careful attention was paid to curating the collected RecA sequences since ProfileGrids allow the easy identification of rare residues in an alignment. We relate the RecA alignment sequence conservation to the following three topics: the recently identified DNA binding residues, the unexplored MAW motif, and a unique Bacillus subtilis RecA homolog sequence feature. Conclusion ProfileGrids allow large protein families to be visualized more effectively than the traditional stacked sequence alignment form. This new graphical representation facilitates the determination of the sequence conservation at residue positions of interest, enables the examination of structural patterns by using residue physical properties, and permits the display of rare sequence features within the context of an entire alignment. JProfileGrid is free for non-commercial use and is available from . Furthermore, we present a curated RecA protein collection that is more diverse than previous data sets; and, therefore, this RecA ProfileGrid is a rich source of information for nanoanatomy analysis.

Roca, Alberto I; Almada, Albert E; Abajian, Aaron C

2008-01-01

270

Familial Progressive Sensorimotor Neuropathy with Agenesis of the Corpus callosum (Andermann Syndrome): A Clinical, Neuroradiological and Histopathological Study  

Microsoft Academic Search

Three siblings from consanguineous parents, originating from Tanzania, presented with symptoms of complete or partial agenesis of the corpus callosum. Two males had in addition a sensorimotor neuropathy, moderate mental retardation and skeletal dysmorphism (Andermann syndrome). A study of sural nerve biopsies revealed thickening of the perineurium and reduction in the number of large myelinated fibres with axonal degeneration. Muscle

Dirk Deleu; Sunita A. Bamanikar; David Muirhead; Andre Louon

1997-01-01

271

Family Interactions in Adoptive Compared to Nonadoptive Families  

Microsoft Academic Search

Despite the large and growing numbers of adoptive families, little research describes interactions in families with adopted adolescents. Yet, adopted adolescents' increased risk for adjustment problems, combined with the association between family interactions and adolescent adjustment in nonadoptive families, raises questions about differences in adoptive and nonadoptive family interactions. We compared observed and self-reported family interactions between 284 adoptive and

Martha A. Rueter; Margaret A. Keyes; William G. Iacono; Matt McGue

2009-01-01

272

Identification of mutation c.632G>A (p.G211D) in the ATP2A2 gene and genotype-phenotype correlation in a large Chinese family with Darier's disease.  

PubMed

Darier's disease (DD, MIM 124200) is an autosomal dominant inherited skin disease. Mutations in the ATP2A2 gene, which encoded the sarcoplasmic/endoplasmic reticulum Ca(2+) -ATPase isoform 2 (SERCA2), are responsible for this skin disorder. Here we report the clinical, genetic, and molecular characterization of a large Chinese family with DD. We identified mutation c.632G>A (p.G211D) in the ATP2A2 gene in this family. Genotype-phenotype correlation in available family members provided helpful genetic counseling information for mutation carriers. PMID:22004489

Lu, Feng-Yan; Xu, Ling; Yin, Xun-Guo; Wan, Ping; Zhang, Xiao-De; Chen, Wei-Wen; Ding, Shao-Ping; Yao, Yong-Gang

2011-11-01

273

A splice-site mutation leads to haploinsufficiency of EXT2 mRNA for a dominant trait in a large family with multiple osteochondromas.  

PubMed

Multiple osteochondromas (MO) is an autosomal-dominant disorder and mutations in EXT1 and EXT2 account up to 78% of the cases studied, including missense, nonsense, frameshift, and splice-site mutations. EXT1 and EXT2 encode glycosyltransferases required for the synthesis of heparan sulfate (HS) chains. The molecular pathogenesis underlying these mutations is still largely unknown. A heterozygous c.1173?+ 1G > T (EXT2) mutation was identified in a three-generation 34-member MO family and is present in all 19 affected members. The consequence of this mutation is exon 7 being spliced out, and the result is a shift in the codon-reading frame from position 360 (R360) of the amino acid sequence leading to a premature termination codon, and the mutant mRNA is degraded to an undetectable level. Interestingly, HS glycosaminoglycans were also undetectable in the cartilage cap of the tumors by immunostaining. Full penetrance of this mutation in all affected members ranging from 5 to 70 years of age suggests this primary defect in EXT2 mRNA level, in conjunction with other cellular changes such as enhanced heparanase expression, can produce profound effect on the synthesis of HS chains in cartilage, the consequence of which impacts on the regulation of chondrocyte proliferation and differentiation. PMID:20872591

Yang, Liu; Hui, Wing Sum; Chan, Wilson C W; Ng, Vivian C W; Yam, Teresa H Y; Leung, Helen C M; Huang, Jian-Dong; Shum, Daisy K Y; Jie, Qiang; Cheung, Kenneth M C; Cheah, Kathryn S E; Luo, Zhoujing; Chan, Danny

2010-11-01

274

A Missense Mutation in the Alpha-Actinin 1 Gene (ACTN1) Is the Cause of Autosomal Dominant Macrothrombocytopenia in a Large French Family.  

PubMed

Inherited thrombocytopenia is a heterogeneous group of disorders characterized by a reduced number of blood platelets. Despite the identification of nearly 20 causative genes in the past decade, approximately half of all subjects with inherited thrombocytopenia still remain unexplained in terms of the underlying pathogenic mechanisms. Here we report a six-generation French pedigree with an autosomal dominant mode of inheritance and the identification of its genetic basis. Of the 55 subjects available for analysis, 26 were diagnosed with isolated macrothrombocytopenia. Genome-wide linkage analysis mapped a 10.9 Mb locus to chromosome 14 (14q22) with a LOD score of 7.6. Candidate gene analysis complemented by targeted next-generation sequencing identified a missense mutation (c.137GA; p.Arg46Gln) in the alpha-actinin 1 gene (ACTN1) that segregated with macrothrombocytopenia in this large pedigree. The missense mutation occurred within actin-binding domain of alpha-actinin 1, a functionally critical domain that crosslinks actin filaments into bundles. The evaluation of cultured mutation-harboring megakaryocytes by electron microscopy and the immunofluorescence examination of transfected COS-7 cells suggested that the mutation causes disorganization of the cellular cytoplasm. Our study concurred with a recently published whole-exome sequence analysis of six small Japanese families with congenital macrothrombocytopenia, adding ACTN1 to the growing list of thrombocytopenia genes. PMID:24069336

Guéguen, Paul; Rouault, Karen; Chen, Jian-Min; Raguénès, Odile; Fichou, Yann; Hardy, Elisabeth; Gobin, Eric; Pan-Petesch, Brigitte; Kerbiriou, Mathieu; Trouvé, Pascal; Marcorelles, Pascale; Abgrall, Jean-Francois; Le Maréchal, Cédric; Férec, Claude

2013-09-17

275

A Missense Mutation in the Alpha-Actinin 1 Gene (ACTN1) Is the Cause of Autosomal Dominant Macrothrombocytopenia in a Large French Family  

PubMed Central

Inherited thrombocytopenia is a heterogeneous group of disorders characterized by a reduced number of blood platelets. Despite the identification of nearly 20 causative genes in the past decade, approximately half of all subjects with inherited thrombocytopenia still remain unexplained in terms of the underlying pathogenic mechanisms. Here we report a six-generation French pedigree with an autosomal dominant mode of inheritance and the identification of its genetic basis. Of the 55 subjects available for analysis, 26 were diagnosed with isolated macrothrombocytopenia. Genome-wide linkage analysis mapped a 10.9 Mb locus to chromosome 14 (14q22) with a LOD score of 7.6. Candidate gene analysis complemented by targeted next-generation sequencing identified a missense mutation (c.137GA; p.Arg46Gln) in the alpha-actinin 1 gene (ACTN1) that segregated with macrothrombocytopenia in this large pedigree. The missense mutation occurred within actin-binding domain of alpha-actinin 1, a functionally critical domain that crosslinks actin filaments into bundles. The evaluation of cultured mutation-harboring megakaryocytes by electron microscopy and the immunofluorescence examination of transfected COS-7 cells suggested that the mutation causes disorganization of the cellular cytoplasm. Our study concurred with a recently published whole-exome sequence analysis of six small Japanese families with congenital macrothrombocytopenia, adding ACTN1 to the growing list of thrombocytopenia genes.

Gueguen, Paul; Rouault, Karen; Chen, Jian-Min; Raguenes, Odile; Fichou, Yann; Hardy, Elisabeth; Gobin, Eric; Pan-petesch, Brigitte; Kerbiriou, Mathieu; Trouve, Pascal; Marcorelles, Pascale; Abgrall, Jean-francois; Le Marechal, Cedric; Ferec, Claude

2013-01-01

276

A novel c.2T > C mutation of the KDM5C/JARID1C gene in one large family with X-linked intellectual disability.  

PubMed

Mutations in the KDM5C gene (lysine (K)-specific demethylase 5C gene; also known as JARID1C and SMCX; MIM 314690) were recently associated with X-linked intellectual disability (XLID). To date only two case reports and five studies that screen for mutations in the KDM5C gene have been published, with 21 mutations reported. Herein we present a large family with XLID caused by a novel mutation c.2T > C in the start codon of the KDM5C gene, presumably leading to loss of gene translation. Six sibs out of seven (two sons and four sisters) and their mother carry this mutation. Two affected males presented the distinctive clinical phenotype, characterized by moderate short stature, clumsy gait, ataxia, increased muscle tone and brisk tendon reflexes. They constantly bore a happy and smiling facial expression, with a protruding tongue. We hereby offer the first thorough description of five affected females with the KDM5C gene mutation. Most frequent clinical features were short stature, facial dysmorphism and developmental problems. X-chromosome inactivation study showed completely skewed inactivation pattern of mutation-carrying chromosome in all affected female patients. PMID:22326837

Ounap, Katrin; Puusepp-Benazzouz, Helen; Peters, Maire; Vaher, Ulvi; Rein, Reet; Proos, Anne; Field, Mike; Reimand, Tiia

2012-01-21

277

Familial Sneddon's syndrome.  

PubMed

A syndrome associating Livedo Reticularis (LR) with Cerebrovascular disease (CVD) was described, in 1965, by Sneddon. It occurs sporadically, but a few familial cases of Sneddon's Syndrome (SS) have been reported, like these 3 cases that represent one of the largest number among siblings. We studied three male brothers, aged 28, 37 and 42 years, with CVD (ischaemic stroke in 2 patients and cerebral haemorrhages in the third) and their sister with no CVD. All patients presented with long lasting Livedo Reticularis, extending beyond the lower limbs. Skin biopsy on the centre of the reticular pattern showed, only in the second patient, partial endothelium detachment in dermo-hypodermic blood vessels. The males also had accesses of Livedoid Vasculitis (LV), in which a skin biopsy showed obliteration of several upper dermal vessels with hialin thrombi and a very scarce inflammatory infiltrate. Complementary studies, with an extensive investigation on pro-coagulation/pro-thrombotic features including antiphospholipid antibodies, were repeatedly negative. Their non-consanguineous parents were not affected, but among these kindred of 9 individuals, apart from the 4 patients reported above, LR and LV were present in two other brothers and also in an aunt and uncle, suggesting autosomal dominant pattern of inheritance, with incomplete penetrance. The relationship between Sneddon's Syndrome and Antiphospholipid Antibody Syndrome is controversial. The present cases, having repeatedly negative antiphospholipid antibodies, support the classification of Sneddon's Syndrome as an independent nosological entity. PMID:12804991

Mascarenhas, Rosa; Santo, Gustavo; Gonçalo, Margarida; Ferro, Maria Antonia; Tellechea, Oscar; Figueiredo, Américo

278

[Familial congenital hypomagnesemia revealed by neonatal convulsions].  

PubMed

Congenital hypomagnesemia is a rare disease, with an impact on cognitive and neurological development. We report on three familial cases of congenital hypomagnesemia, two boys and one girl who belong to the same consanguineous family. They all presented neonatal seizures and a psychomotor developmental delay. Cerebral computed tomography showed cerebral atrophy and calcifications in one case and magnetic resonance imaging found predominant cerebellar atrophy in the two other cases. All three patients also had hypocalcemia, hyperphosphoremia, and hypomagnesemia. The parathyroid hormone blood level was low in two cases and normal in the third. One 7-month old patient died. The others received a supplementation of calcium and magnesium, which normalized calcemia, phosphatemia but not magnesemia, which remained low despite high doses. They have both developed cognitive and behavioral impairments. PMID:24090669

Ndiaye, M; Dehanin, T; Sow, A-D; Sène, M-S; Basse, A-M; Fall, A-L; Seck, L-B; Touré, K; Diop, A-G; Sow, H-D; Ndiaye, M-M

2013-09-30

279

Large-scale Molecular Analysis of a 34 Mb Interval on Chromosome 6q: Major Refinement of the RP25 Interval  

PubMed Central

Summary A large scale bioinformatics and molecular analysis of a 34 Mb interval on chromosome 6q12 was undertaken as part of our ongoing study to identify the gene responsible for an autosomal recessive retinitis pigmentosa (arRP) locus, RP25. Extensive bioinformatics analysis indicated in excess of 110 genes within the region and we also noted unfinished sequence on chromosome 6q in the Human Genome Database, between 58 and 61.2 Mb. Forty three genes within the RP25 interval were considered as good candidates for mutation screening. Direct sequence analysis of the selected genes in 7 Spanish families with arRP revealed a total of 244 sequence variants, of which 67 were novel but none were pathogenic. This, together with previous reports, excludes 60 genes within the interval (~55%) as disease causing for RP. To investigate if copy number variation (CNV) exists within RP25, a comparative genomic hybridization (CGH) analysis was performed on a consanguineous family. A clone from the tiling path array, chr6tp-19C7, spanning ~100-Kb was found to be deleted in all affected members of the family, leading to a major refinement of the interval. This will eventually have a significant impact on cloning of the RP25 gene.

El-Aziz, M. M. Abd; Barragan, I.; O'Driscoll, C.; Borrego, S.; Abu-Safieh, L.; Pieras, J. I.; El-Ashry, M. F.; Prigmore, E.; Carter, N.; Antinolo, G.; Bhattacharya, S. S.

2009-01-01

280

Mob families and mad families  

Microsoft Academic Search

.   We show the consistency of where is the size of the smallest off-branch family, and is as usual the dominating number. We also prove the consistency of with large continuum. Here, is the unbounding number, and is the almost disjointness number.

Jörg Brendle

1998-01-01

281

Giant cell tumor occurring in familial Paget's disease of bone: report of clinical characteristics and linkage analysis of a large pedigree.  

PubMed

Neoplastic degeneration represents a rare but serious complication of Paget's disease of bone (PDB). Although osteosarcomas have been described in up to 1% of PDB cases, giant cell tumors are less frequent and mainly occur in patients with polyostotic disease. We recently characterized a large pedigree with 14 affected members of whom four developed giant cell tumors at pagetic sites. The high number of affected subjects across multiple generations allowed us to better characterize the clinical phenotype and look for possible susceptibility loci. Of interest, all the affected members had polyostotic PDB, but subjects developing giant cell tumors showed an increased disease severity with a reduced clinical response to bisphosphonate treatment and an increased prevalence of bone pain, deformities, and fractures. Together with an increased occurrence of common pagetic complications, affected patients of this pedigree also evidenced a fivefold higher prevalence of coronary artery disease with respect to either the unaffected family members or a comparative cohort of 150 unrelated PDB cases from the same geographical area. This association was further enhanced in the four cases with PDB and giant cell tumors, all of them developing coronary artery disease before 60 years of age. Despite the early onset and the severe phenotype, PDB patients from this pedigree were negative for the presence of SQSTM1 or TNFRSF11A mutations, previously associated with enhanced disease severity. Genome-wide linkage analysis identified six possible candidate regions on chromosomes 1, 5, 6, 8, 10, and 20. Because the chromosome 8 and 10 loci were next to the TNFRSF11B and OPTN genes, we extended the genetic screening to these two genes, but we failed to identify any causative mutation at both the genomic and transcription level, suggesting that a different genetic defect is associated with PDB and potentially giant cell tumor of bone in this pedigree. PMID:22936311

Gianfrancesco, Fernando; Rendina, Domenico; Merlotti, Daniela; Esposito, Teresa; Amyere, Mustapha; Formicola, Daniela; Muscariello, Riccardo; De Filippo, Gianpaolo; Strazzullo, Pasquale; Nuti, Ranuccio; Vikkula, Mikka; Gennari, Luigi

2013-02-01

282

The mitochondrial tRNA Ala T5628C variant may have a modifying role in the phenotypic manifestation of the 12S rRNA C1494T mutation in a large Chinese family with hearing loss  

Microsoft Academic Search

We report here the clinical, genetic, and molecular characterization of a large Han Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. Two and 13 of 66 matrilineal relatives suffered from aminoglycoside-induced and nonsyndromic hearing loss, respectively. These matrilineal relatives exhibited a wide range of severity of hearing loss, varying from profound to normal hearing. In the absence of aminoglycosides, the

Dongyi Han; Pu Dai; Qingwen Zhu; Xin Liu; Deliang Huang; Yongyi Yuan; Huijun Yuan; Xinjian Wang; Yaping Qian; Wie-Yen Young; Min-Xin Guan

2007-01-01

283

Heritability of determinants of the metabolic syndrome among healthy Arabs of the Oman family study.  

PubMed

The metabolic syndrome, as defined by the International Diabetes Federation, was investigated in five large, extended, highly consanguineous, healthy Omani Arab families of a total of 1277 individuals. Heritability (h2) of the phenotypic abnormalities that make up the syndrome and other related traits was estimated by variance decomposition method using SOLAR software. The overall prevalence of the syndrome was 23%. The prevalence of abnormalities making the syndrome in a descending order were: obligatory waist circumference, hypertension, raised fasting blood glucose, low serum high-density lipoprotein (HDL), and raised serum triglycerides (TGs). Highly significant, but widely spread, h2 values were obtained for: height (0.68), weight (0.68), BMI (0.68), serum HDL (0.63), serum leptin (0.55), percentage body fat (0.53), total serum cholesterol (0.53), fasting serum insulin (0.51), homeostasis model assessment-insulin resistance index (0.48), serum TG (0.43), waist circumference (0.40), diastolic blood pressure (0.38), and 2-hour glucose level (0.17), whereas for the metabolic syndrome itself, h2 was 0.38. The wide spread of h2 results (0.07 to 0.68) indicates that some determinants, such as weight, BMI, and HDL level, are under significant genetic influence among the Omani Arabs. Other determinants such as insulin resistance, abdominal obesity, diastolic blood pressure, and TG levels seem to be more environmentally driven. PMID:17372303

Bayoumi, Riad A; Al-Yahyaee, Saeed A S; Albarwani, Sulayma A; Rizvi, Syed G; Al-Hadabi, Saleh; Al-Ubaidi, Firial F; Al-Hinai, Ali T; Al-Kindi, Mohammed N; Adnan, Haleema T; Al-Barwany, Hameeda S; Comuzzie, Antony G; Cai, Guowen; Lopez-Alvarenga, Juan C; Hassan, Mohammed O

2007-03-01

284

Prenatal Diagnosis of Diffuse Mesangial Glomerulosclerosis by Ultrasonography: A Longitudinal Study of a Case in an Affected Family  

Microsoft Academic Search

The 4th child of an Arabian consanguineous family with 2 previous infant deaths due to diffuse mesangial glomerulosclerosis (at the ages of 1 and 44 days) and 1 healthy 3-year old child was followed up by ultrasonography from the 9th until the 35th week of gestation. Ultrasound showed enlarged hyperechogenic kidneys from the 14th week onwards, and the amniotic fluid

C. Hofstaetter; I. Neumann; T. Lennert; J. W. Dudenhausen

1996-01-01

285

Identification and Gene Expression Analysis of a Large Family of Transmembrane Kinases Related to the Gal\\/GalNAc Lectin in Entamoeba histolytica  

Microsoft Academic Search

We identified in the Entamoeba histolytica genome a family of over 80 putative transmembrane kinases (TMKs). The TMK extracellular domains had significant similarity to the intermediate subunit (Igl) of the parasite Gal\\/GalNAc lectin. The closest homolog to the E. histolytica TMK kinase domain was a cytoplasmic dual-specificity kinase, SplA, from Dictyostelium discoideum. Sequence analysis of the TMK family demon- strated

David L. Beck; Douglas R. Boettner; Bojan Dragulev; Kim Ready; Tomoyoshi Nozaki; William A. Petri

2005-01-01

286

Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes.  

PubMed Central

A cDNA corresponding to a thiol-specific antioxidant enzyme (TSA) was isolated from a rat brain cDNA library with the use of antibodies to bovine TSA. The cDNA clone encoded an open reading frame capable of encoding a 198-residue polypeptide. The rat and yeast TSA proteins show significant sequence homology to the 21-kDa component (AhpC) of Salmonella typhimurium alkyl hydroperoxide reductase, and we have found that AhpC exhibits TSA activity. AhpC and TSA define a family of > 25 different proteins present in organisms from all kingdoms. The similarity among the family members extends over the entire sequence and ranges between 23% and 98% identity. A majority of the members of the AhpC/TSA family contain two conserved cysteines. At least eight of the genes encoding AhpC/TSA-like polypeptides are found in proximity to genes encoding other oxidoreductase activities, and the expression of several of the homologs has been correlated with pathogenicity. We suggest that the AhpC/TSA family represents a widely distributed class of antioxidant enzymes. We also report that a second family of proteins, defined by the 57-kDa component (AhpF) of alkyl hydroperoxide reductase and by thioredoxin reductase, has expanded to include six additional members.

Chae, H Z; Robison, K; Poole, L B; Church, G; Storz, G; Rhee, S G

1994-01-01

287

Hirayama Family  

NASA Astrophysics Data System (ADS)

Any of several groups of asteroids each of whose members share similar orbital elements, in particular a closely similar semi-major axis and orbital inclination. These similarities are surmised to indicate that the members of a particular Hirayama family share a common origin in the collisional break-up of a large parent body. The existence of such groups were first pointed out by Kiyotsugu Hiray...

Murdin, P.

2000-11-01

288

The Clinical Spectrum of Missense Mutations of the First Aspartic Acid of cbEGF-like Domains in Fibrillin-1 Including a Recessive Family  

PubMed Central

Marfan syndrome (MFS) is a dominant disorder with a recognizable phenotype. In most patients with the classical phenotype mutations are found in the fibrillin-1 gene (FBN1) on chromosome 15q21. It is thought that most mutations act in a dominant negative way or through haploinsufficiency. In 9 index cases referred for MFS we detected heterozygous missense mutations in FBN1 predicted to substitute the first aspartic acid of different calcium-binding Epidermal Growth Factor-like (cbEGF) fibrillin-1 domains. A similar mutation was found in homozygous state in 3 cases in a large consanguineous family. Heterozygous carriers of this mutation had no major skeletal, cardiovascular or ophthalmological features of MFS. In the literature 14 other heterozygous missense mutations are described leading to the substitution of the first aspartic acid of a cbEGF domain and resulting in a Marfan phenotype. Our data show that the phenotypic effect of aspartic acid substitutions in the first position of a cbEGF domain can range from asymptomatic to a severe neonatal phenotype. The recessive nature with reduced expression of FBN1 in one of the families suggests a threshold model combined with a mild functional defect of this specific mutation. © 2010 Wiley-Liss, Inc.

Hilhorst-Hofstee, Yvonne; Rijlaarsdam, Marry EB; Scholte, Arthur JHA; Swart-van den Berg, Marietta; Versteegh, Michel IM; van der Schoot-van Velzen, Iris; Schabitz, Hans-Joachim; Bijlsma, Emilia K; Baars, Marieke J; Kerstjens-Frederikse, Wilhelmina S; Giltay, Jacques C; Hamel, Ben C; Breuning, Martijn H; Pals, Gerard

2010-01-01

289

Familiality of Tourette Syndrome, Obsessive-Compulsive Disorder, and Attention-Deficit/Hyperactivity Disorder: Heritability Analysis in a Large Sib-Pair Sample  

ERIC Educational Resources Information Center

|Objective: Tourette syndrome (TS) is a neuropsychiatric disorder with a genetic component that is highly comorbid with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). However, the genetic relations between these disorders have not been clearly elucidated. This study examined the familial relations among…

Mathews, Carol A.; Grados, Marco A.

2011-01-01

290

Sfr13, a member of a large family of asymmetrically localized Sfi1-repeat proteins, is important for basal body separation and stability in Tetrahymena thermophila.  

PubMed

Directed fluid flow, which is achieved by the coordinated beating of motile cilia, is required for processes as diverse as cellular swimming, developmental patterning and mucus clearance. Cilia are nucleated, anchored and aligned at the plasma membrane by basal bodies, which are cylindrical microtubule-based structures with ninefold radial symmetry. In the unicellular ciliate Tetrahymena thermophila, two centrin family members associated with the basal body are important for both basal body organization and stabilization. We have identified a family of 13 proteins in Tetrahymena that contain centrin-binding repeats related to those identified in the Saccharomyces cerevisiae Sfi1 protein. We have named these proteins Sfr1-Sfr13 (for Sfi1-repeat). Nine of the Sfr proteins localize in unique polarized patterns surrounding the basal body, suggesting non-identical roles in basal body organization and association with basal body accessory structures. Furthermore, the Sfr proteins are found in distinct basal body populations in Tetrahymena cells, indicating that they are responsive to particular developmental programs. A complete genetic deletion of one of the family members, Sfr13, causes unstable basal bodies and defects in daughter basal body separation from the mother, phenotypes also observed with centrin disruption. It is likely that the other Sfr family members are involved in distinct centrin functions, providing specificity to the tasks that centrins perform at basal bodies. PMID:23426847

Stemm-Wolf, Alexander J; Meehl, Janet B; Winey, Mark

2013-02-20

291

Association of PPAR?2 gene variant Pro12Ala polymorphism with hypertension and obesity in the aboriginal Qatari population known for being consanguineous  

PubMed Central

Aim The aim of this study was to investigate the association of the Pro12Ala polymorphism of the human peroxisome proliferator-activated receptor gamma 2 (PPAR?2) gene with hypertension and obesity in a highly consanguineous aboriginal Qatari population. Design A cross-sectional survey conducted from January 2011–December 2012. Setting Primary health care clinics. Subjects A random sample of 1,528 Qatari male and female population older than 20 years of age. Materials and methods Data on age, sex, income, level of education, occupation status, body mass index, and blood pressure and lipid profile were obtained. The Pro12Ala in the PPAR?2 gene was detected on the LightCycler® using two specific probes: (Sensor [G] 5?-CTC CTA TTG ACG CAG AAA GCG-FL and PPAR Anchor 5? LC Red 640- TCC TTC ACT GAT ACA CTG TCT GCA AAC ATA TC-PH). Univariate and multivariate logistic regression were performed. Result Out of a total 1,528 participants, 220 were diagnosed with essential hypertension, and 420 were obese. Participants with consanguinity were significantly higher among hypertensive than normotensive (41.9% versus 30.8%; P=0.001). Altogether, more than three-fourths (89%) of the participants had a wild genotype (Pro12Pro), 9.8% were heterozygous with Pro12Ala, and only 1.2% was homozygous with the Ala12Ala genotype. The frequency of the Pro allele was 94.5% in normotensive versus 90.5% in hypertensive, while the distribution of the Ala allele was 5.5% in normotensive versus 9.5% in the hypertensive group (P=0.001). The odds of hypertension were 1.7 times higher among the participants with the Ala allele as compared to those with the Pro, while adjusting for other potential confounders (adjusted odds ratio 1.69; 95% confidence interval 1.12–2.55; P=0.012). There was no association between the PPAR?2Ala allele and obesity (P=0.740). Conclusion The current study revealed an association between the PPAR?2Ala allele and hypertension in Qatar’s population. On the other hand, this study found no association between the Ala allele and obesity.

Bener, Abdulbari; Darwish, Sarah; Al-Hamaq, Abdulla OAA; Mohammad, Ramzi M; Yousafzai, Mohammad T

2013-01-01

292

Clinical and Molecular Evidence of Abnormal Processing and Trafficking of the Vasopressin Preprohormone in a Large Kindred with Familial Neurohypophyseal Diabetes Insipidus due to A Signal Peptide Mutation  

Microsoft Academic Search

The autosomal dominant form of familial neurohypophyseal dia- betes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations of the gene that codes for the vaso- pressin-neurophysin II (AVP-NPII) precursor. The aims of the present study

CHARLOTTE SIGGAARD; SØREN RITTIG; THOMAS J. CORYDON; PER HOVE ANDREASEN; THOMAS G. JENSEN; BRAGE S. ANDRESEN; GARY L. ROBERTSON; NIELS GREGERSEN; LARS BOLUND; ERLING B. PEDERSEN

293

A large family with subtelomeric translocation t(18;21)(q23;q22.1) and molecular breakpoint in the Down syndrome critical region  

Microsoft Academic Search

We describe a 17-month-old infant with clinical features of Down syndrome and a normal karyotype by standard chromosomal analysis,\\u000a her two uncles aged 28 and 30 years, respectively, with reduced intelligence and unusual appearance but not apparent Down\\u000a syndrome, and a severely retarded 6-year-old girl with dysmorphy and epilepsy from the same family. Cytogenetic studies of\\u000a patients and normal intervening

Oliver Bartsch; Georg K. Hinkel; Michael B. Petersen; Ulrich König; Merete Bugge; Margareta Mikkelsen; Dimitris Avramopoulos; Michael Morris; Stylianos E. Antonarakis

1997-01-01

294

Diaspora, a large family of Ty3-gypsy retrotransposons in Glycine max, is an envelope-less member of an endogenous plant retrovirus lineage  

PubMed Central

Background The chromosomes of higher plants are littered with retrotransposons that, in many cases, constitute as much as 80% of plant genomes. Long terminal repeat retrotransposons have been especially successful colonizers of the chromosomes of higher plants and examinations of their function, evolution, and dispersal are essential to understanding the evolution of eukaryotic genomes. In soybean, several families of retrotransposons have been identified, including at least two that, by virtue of the presence of an envelope-like gene, may constitute endogenous retroviruses. However, most elements are highly degenerate and are often sequestered in regions of the genome that sequencing projects initially shun. In addition, finding potentially functional copies from genomic DNA is rare. This study provides a mechanism to surmount these issues to generate a consensus sequence that can then be functionally and phylogenetically evaluated. Results Diaspora is a multicopy member of the Ty3-gypsy-like family of LTR retrotransposons and comprises at least 0.5% of the soybean genome. Although the Diaspora family is highly degenerate, and with the exception of this report, is not represented in the Genbank nr database, a full-length consensus sequence was generated from short overlapping sequences using a combination of experimental and in silico methods. Diaspora is 11,737 bp in length and contains a single 1892-codon ORF that encodes a gag-pol polyprotein. Phylogenetic analysis indicates that it is closely related to Athila and Calypso retroelements from Arabidopsis and soybean, respectively. These in turn form the framework of an endogenous retrovirus lineage whose members possess an envelope-like gene. Diaspora appears to lack any trace of this coding region. Conclusion A combination of empirical sequencing and retrieval of unannotated Genome Survey Sequence database entries was successfully used to construct a full-length representative of the Diaspora family in Glycine max. Diaspora is presently the only fully characterized member of a lineage of putative plant endogenous retroviruses that contains virtually no trace of an extra coding region. The loss of an envelope-like coding domain suggests that non-infectious retrotransposons could swiftly evolve from infectious retroviruses, possibly by anomalous splicing of genomic RNA.

Yano, Sho T; Panbehi, Bahman; Das, Arpita; Laten, Howard M

2005-01-01

295

Large-scale, lineage-specific expansion of a bric-a-brac/tramtrack/broad complex ubiquitin-ligase gene family in rice.  

PubMed

Selective ubiquitination of proteins is directed by diverse families of ubiquitin-protein ligases (or E3s) in plants. One important type uses Cullin-3 as a scaffold to assemble multisubunit E3 complexes containing one of a multitude of bric-a-brac/tramtrack/broad complex (BTB) proteins that function as substrate recognition factors. We previously described the 80-member BTB gene superfamily in Arabidopsis thaliana. Here, we describe the complete BTB superfamily in rice (Oryza sativa spp japonica cv Nipponbare) that contains 149 BTB domain-encoding genes and 43 putative pseudogenes. Amino acid sequence comparisons of the rice and Arabidopsis superfamilies revealed a near equal repertoire of putative substrate recognition module types. However, phylogenetic comparisons detected numerous gene duplication and/or loss events since the rice and Arabidopsis BTB lineages split, suggesting possible functional specialization within individual BTB families. In particular, a major expansion and diversification of a subset of BTB proteins containing Meprin and TRAF homology (MATH) substrate recognition sites was evident in rice and other monocots that likely occurred following the monocot/dicot split. The MATH domain of a subset appears to have evolved significantly faster than those in a smaller core subset that predates flowering plants, suggesting that the substrate recognition module in many monocot MATH-BTB E3s are diversifying to ubiquitinate a set of substrates that are themselves rapidly changing. Intriguing possibilities include pathogen proteins attempting to avoid inactivation by the monocot host. PMID:17720868

Gingerich, Derek J; Hanada, Kousuke; Shiu, Shin-Han; Vierstra, Richard D

2007-08-24

296

A homozygous p.Glu150Lys mutation in the opsin gene of two Pakistani families with autosomal recessive retinitis pigmentosa  

PubMed Central

Purpose To identify the gene mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in Pakistani families. Methods A cohort of consanguineous families with typical RP phenotype in patients was screened by homozygosity mapping using microsatellite markers that mapped close to 21 known arRP genes and five arRP loci. Mutation analysis was performed by direct sequencing of the candidate gene. Results In two families, RP21 and RP53, homozygosity mapping suggested RHO, the gene encoding rhodopsin, as a candidate disease gene on chromosome 3q21. In six out of seven affected members from the two families, direct sequencing of RHO identified a homozygous c.448G>A mutation resulting in the p.Glu150Lys amino acid change. This variant was first reported in PMK197, an Indian arRP family. Single nucleotide polymorphism analysis in RP21, RP53, and PMK197 showed a common disease-associated haplotype in the three families. Conclusions In two consanguineous Pakistani families with typical arRP phenotype in the patients, we identified a disease-causing mutation (p.Glu150Lys) in the RHO gene. Single nucleotide polymorphism analysis suggests that the previously reported Indian family (PMK197) and the two Pakistani families studied here share the RHO p.Glu150Lys mutation due to a common ancestry.

Azam, Maleeha; Khan, Muhammad Imran; Gal, Andreas; Hussain, Alamdar; Shah, Syed Tahir Abbas; Khan, Muhammad Shakil; Sadeque, Ahmed; Bokhari, Habib; Collin, Rob W.J.; Orth, Ulrike; van Genderen, Maria M.; den Hollander, A.I.; Cremers, Frans P. M.

2009-01-01

297

Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma.  

PubMed

Charcot-Marie-Tooth disease (CMT) with autosomal recessive (AR) inheritance is a heterogeneous group of inherited motor and sensory neuropathies. In some families from Japan and Brazil, a demyelinating CMT, mainly characterized by the presence of myelin outfoldings on nerve biopsies, cosegregated as an autosomal recessive trait with early-onset glaucoma. We identified two such large consanguineous families from Tunisia and Morocco with ages at onset ranging from 2 to 15 years. We mapped this syndrome to chromosome 11p15, in a 4.6-cM region overlapping the locus for an isolated demyelinating ARCMT (CMT4B2). In these two families, we identified two different nonsense mutations in the myotubularin-related 13 gene, MTMR13. The MTMR protein family includes proteins with a phosphoinositide phosphatase activity, as well as proteins in which key catalytic residues are missing and that are thus called "pseudophosphatases." MTM1, the first identified member of this family, and MTMR2 are responsible for X-linked myotubular myopathy and Charcot-Marie-Tooth disease type 4B1, an isolated peripheral neuropathy with myelin outfoldings, respectively. Both encode active phosphatases. It is striking to note that mutations in MTMR13 also cause peripheral neuropathy with myelin outfoldings, although it belongs to a pseudophosphatase subgroup, since its closest homologue is MTMR5/Sbf1. This is the first human disease caused by mutation in a pseudophosphatase, emphasizing the important function of these putatively inactive enzymes. MTMR13 may be important for the development of both the peripheral nerves and the trabeculum meshwork, which permits the outflow of the aqueous humor. Both of these tissues have the same embryonic origin. PMID:12687498

Azzedine, H; Bolino, A; Taïeb, T; Birouk, N; Di Duca, M; Bouhouche, A; Benamou, S; Mrabet, A; Hammadouche, T; Chkili, T; Gouider, R; Ravazzolo, R; Brice, A; Laporte, J; LeGuern, E

2003-04-08

298

Mutations in MTMR13, a New Pseudophosphatase Homologue of MTMR2 and Sbf1, in Two Families with an Autosomal Recessive Demyelinating Form of Charcot-Marie-Tooth Disease Associated with Early-Onset Glaucoma  

PubMed Central

Charcot-Marie-Tooth disease (CMT) with autosomal recessive (AR) inheritance is a heterogeneous group of inherited motor and sensory neuropathies. In some families from Japan and Brazil, a demyelinating CMT, mainly characterized by the presence of myelin outfoldings on nerve biopsies, cosegregated as an autosomal recessive trait with early-onset glaucoma. We identified two such large consanguineous families from Tunisia and Morocco with ages at onset ranging from 2 to 15 years. We mapped this syndrome to chromosome 11p15, in a 4.6-cM region overlapping the locus for an isolated demyelinating ARCMT (CMT4B2). In these two families, we identified two different nonsense mutations in the myotubularin-related 13 gene, MTMR13. The MTMR protein family includes proteins with a phosphoinositide phosphatase activity, as well as proteins in which key catalytic residues are missing and that are thus called “pseudophosphatases.” MTM1, the first identified member of this family, and MTMR2 are responsible for X-linked myotubular myopathy and Charcot-Marie-Tooth disease type 4B1, an isolated peripheral neuropathy with myelin outfoldings, respectively. Both encode active phosphatases. It is striking to note that mutations in MTMR13 also cause peripheral neuropathy with myelin outfoldings, although it belongs to a pseudophosphatase subgroup, since its closest homologue is MTMR5/Sbf1. This is the first human disease caused by mutation in a pseudophosphatase, emphasizing the important function of these putatively inactive enzymes. MTMR13 may be important for the development of both the peripheral nerves and the trabeculum meshwork, which permits the outflow of the aqueous humor. Both of these tissues have the same embryonic origin.

Azzedine, H.; Bolino, A.; Taieb, T.; Birouk, N.; Di Duca, M.; Bouhouche, A.; Benamou, S.; Mrabet, A.; Hammadouche, T.; Chkili, T.; Gouider, R.; Ravazzolo, R.; Brice, A.; Laporte, J.; LeGuern, E.

2003-01-01

299

Extending the family of Zn-based MOFs: synthetic approaches to chiral framework structures and MOFs with large pores and channels.  

PubMed

Tri- and pentanuclear, kinetically stable SBUs were exploited for the preparation of the novel MOFs [Zn(3)(BTEB)(2)(DMF)(2)] and (Me(2)NH(2))[Zn(5)(BTEB)(3)(?(3)-OH)(2)(DMF)(2)]. The applied synthetic approach results in topologies that are stabilised by tritopic benzene-trisethynylbenzoic acid (BTEB) linkers giving rise to chiral frameworks with large pores or channels. PMID:22392064

Zhu, Nianyong; Tobin, Gerard; Schmitt, Wolfgang

2012-03-06

300

hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel ? subunit family  

Microsoft Academic Search

We cloned two ? subunits of large-conductance calcium-activated potassium (BK) channels, hKCNMB3 (BK?1) and hKCNMB4 (BK?4). Profiling mRNA expression showed that hKCNMB3 expression is enriched in testis and hKCNMB4 expression is very prominent in brain. We coexpressed BK channel ? (BK?) and BK?4 subunits in vitro in CHO cells. We compared BK?\\/?4 mediated currents with those of smooth muscle BK?\\/?1

R. Behrens; A. Nolting; F. Reimann; M. Schwarz; R. Waldschütz; O. Pongs

2000-01-01

301

X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis.  

PubMed

X-linked congenital adrenal hypoplasia (AHC) is a developmental disorder of the human adrenal gland that results in profound hormonal deficiencies, which are lethal if untreated. Hypogonadotropic hypogonadism (HHG) is frequently associated with this disorder. The gene (DAX-1) responsible for the disease has recently been isolated. It encodes a protein with large similarity to members of the nuclear hormone receptor superfamily. Several different mutations in this gene have been found in patients suffering from AHC. We have identified a missense mutation (N440I) in three patients with AHC and HHG, all belonging to a large Greenlandic family. A total of 42 individuals has been tested for this mutation. We have diagnosed 10 women as carriers, and have excluded 22 women with a 25-50% risk from being carriers, emphasizing the rapid impact of molecular genetic techniques. PMID:9003500

Schwartz, M; Blichfeldt, S; Müller, J

1997-01-01

302

Recombination event at the Friedreich`s ataxia (FRDA) locus in a large French-Canadian family positions the FRDA gene centromeric to the X11 gene  

SciTech Connect

The FRDA gene is closely linked to loci D9S15 (MCT112) and D9S5 (DR47/26P) on chromosome 9q in a region of reduced recombination. We studied three related Quebec families using 11 polymorphic markers spanning {approximately} 1.5 megabases on 9q. They are arranged 9qtel-9qcen as shown. All are multiallelic microsatellites, except for MCT/MspI, DR47 and 26P. We find that two obligate heterozygote siblings: No. 196 (mother of 5 affected children) and No. 179 (father of 1 affected son) gave different FRDA chromosomes to their affected offspring. Both chromosomes originate from their unaffected mother No. 197. A recombination took place so that she transmitted No. 179, on the 2-8-6-1-3-2-2-2-2-3-7 haplotype the mutant FRDA gene. It occurred after FD1/X11 and extends as far as FR5. Lack of informativity at the MLS1 and FR2 loci precludes the detection of a second, unlikely recombination event within the region. This rare recombination places the FRDA gene centromeric to the X11 gene.

Richter, A.; Mercier, J.; Poirier, J. [Univ. of Montreal, Quebec (Canada)] [and others

1994-09-01

303

Functional Family Therapy.  

National Technical Information Service (NTIS)

While a number of States and communities are turning to punitive approaches to addressing juvenile crime, research indicates that such approaches, despite their high cost, are largely ineffective. Juvenile offenders removed from their families and communi...

2008-01-01

304

First Report of Clinical, Functional, and Molecular Investigation of Chronic Granulomatous Disease in Nine Jordanian Families  

Microsoft Academic Search

Introduction  Chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential\\u000a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components.\\u000a \\u000a \\u000a \\u000a Material and methods  Clinical, functional, and molecular investigations were conducted in 15 Jordanian CGD patients from nine families.\\u000a \\u000a \\u000a \\u000a Results and Discussion  Fourteen patients were children of consanguineous parents and suffered from autosomal recessive (AR) CGD forms with

Faris G. Bakri; Cécile Martel; Najwa Khuri-Bulos; Azmi Mahafzah; Mohammad S. El-Khateeb; Adel M. Al-Wahadneh; Wail A. Hayajneh; Hanan A. Hamamy; Elisabeth Maquet; Michelle Molin; Marie José Stasia

2009-01-01

305

Familial tyrosinaemia with eye and skin lesions. Presentation of two cases.  

PubMed

Two cases of tyrosinaemia with eye and skin lesions typical of the Richner-Hanhart syndrome are described. The patients are a 29- and 26-year-old brother and sister. They do not show neurological abnormalities or mental retardation. Parents are not consanguineous and family history is negative for similar conditions. The diagnosis of type II tyrosinaemia was based upon an increase of blood tyrosine (14-16mg/100 ml), tyrosinuria and absence of liver and kidney abnormalities. The treatment with a low tyrosine phenylalanine diet has resulted in a disappearence of the ocular manifestations while the cutaneous lesions are much improved. PMID:20595

Bardelli, A M; Borgogni, P; Farnetani, M A; Fois, A; Frezzotti, R; Mattei, R; Molinelli, M; Sargentini, I

1977-01-01

306

Foster Families  

MedlinePLUS

... foster family? Let's find out. What Are Foster Families? The word "foster" means to help someone (or ... stressful time. Why Do Kids Live With Foster Families? Most often, a kid goes into a foster ...

307

Electrophoretic and immunological comparisons of chloroplast and prokaryotic ribosomal proteins reveal that certain families of large subunit proteins are evolutionarily conserved  

Microsoft Academic Search

Summary Antibodies to individual chloroplast ribosomal (r-)proteins ofChlamydomonas reinhardtii synthesized in either the chloroplast or the cytoplasm were used to examine the relatedness ofChlamydomonas r-proteins to r-proteins from the spinach (Spinacia oleracea) chloroplast,Escherichia coli, and the cyanobacteriumAnabaena 7120. In addition,35S-labeled chloroplast r-proteins from large and small subunits ofC. reinhardtii were coelectrophoresed on 2-D gels with unlabeled r-proteins from similar subunits

Barbara L. Randolph-Anderson; Nicholas W. Gillham; John E. Boynton

1989-01-01

308

RNA Interference Suppression of Genes in Glycosyl Transferase Families 43 and 47 in Wheat Starchy Endosperm Causes Large Decreases in Arabinoxylan Content1[C][W][OPEN  

PubMed Central

The cell walls of wheat (Triticum aestivum) starchy endosperm are dominated by arabinoxylan (AX), accounting for 65% to 70% of the polysaccharide content. Genes within two glycosyl transferase (GT) families, GT43 (IRREGULAR XYLEM9 [IRX9] and IRX14) and GT47 (IRX10), have previously been shown to be involved in the synthesis of the xylan backbone in Arabidopsis, and close homologs of these have been implicated in the synthesis of xylan in other species. Here, homologs of IRX10 TaGT47_2 and IRX9 TaGT43_2, which are highly expressed in wheat starchy endosperm cells, were suppressed by RNA interference (RNAi) constructs driven by a starchy endosperm-specific promoter. The total amount of AX was decreased by 40% to 50% and the degree of arabinosylation was increased by 25% to 30% in transgenic lines carrying either of the transgenes. The cell walls of starchy endosperm in sections of grain from TaGT43_2 and TaGT47_2 RNAi transgenics showed decreased immunolabeling for xylan and arabinoxylan epitopes and approximately 50% decreased cell wall thickness compared with controls. The proportion of AX that was water soluble was not significantly affected, but average AX polymer chain length was decreased in both TaGT43_2 and TaGT47_2 RNAi transgenics. However, the long AX chains seen in controls were absent in TaGT43_2 RNAi transgenics but still present in TaGT47_2 RNAi transgenics. The results support an emerging picture of IRX9-like and IRX10-like proteins acting as key components in the xylan synthesis machinery in both dicots and grasses. Since AX is the main component of dietary fiber in wheat foods, the TaGT43_2 and TaGT47_2 genes are of major importance to human nutrition.

Lovegrove, Alison; Wilkinson, Mark D.; Freeman, Jackie; Pellny, Till K.; Tosi, Paola; Saulnier, Luc; Shewry, Peter R.; Mitchell, Rowan A.C.

2013-01-01

309

Phase-diagram-guided method for growth of a large crystal of glycoside hydrolase family 45 inverting cellulase suitable for neutron structural analysis.  

PubMed

Neutron protein crystallography (NPC) is a powerful tool for determining the hydrogen position and water orientation in proteins, but a much larger protein crystal is needed for NPC than for X-ray crystallography, and thus crystal preparation is a bottleneck. To obtain large protein crystals, it is necessary to know the properties of the target protein in the crystallization solution. Here, a crystal preparation method of fungal cellulase PcCel45A is reported, guided by the phase diagram. Nucleation and precipitation conditions were determined by sitting-drop vapor diffusion. Saturation and unsaturation conditions were evaluated by monitoring crystal dissolution, and a crystallization phase diagram was obtained. To obtain a large crystal, crystallization solution was prepared on a sitting bridge (diameter = 5?mm). Initial crystallization conditions were 40?µl of crystallization solution (40?mg?ml(-1) protein with 30.5% 3-methyl-1,5-pentanediol in 50?mM tris-HCl pH 8.0) with a 1000?µl reservoir (61% 3-methyl-1,5,-pentanediol in 50?mM tris-HCl pH 8.0) at 293?K. After the first crystal appeared, the concentration of precipitant in the reservoir solution was reduced to 60% to prevent formation of further crystals. Finally, we obtained a crystal of 6?mm(3) volume (3?mm × 2?mm × 1?mm), which was suitable for neutron diffraction. PMID:24121328

Nakamura, Akihiko; Ishida, Takuya; Fushinobu, Shinya; Kusaka, Katsuhiro; Tanaka, Ichiro; Inaka, Koji; Higuchi, Yoshiki; Masaki, Mika; Ohta, Kazunori; Kaneko, Satoshi; Niimura, Nobuo; Igarashi, Kiyohiko; Samajima, Masahiro

2013-09-25

310

Phase-diagram-guided method for growth of a large crystal of glycoside hydrolase family 45 inverting cellulase suitable for neutron structural analysis  

PubMed Central

Neutron protein crystallography (NPC) is a powerful tool for determining the hydrogen position and water orientation in proteins, but a much larger protein crystal is needed for NPC than for X-ray crystallography, and thus crystal preparation is a bottleneck. To obtain large protein crystals, it is necessary to know the properties of the target protein in the crystallization solution. Here, a crystal preparation method of fungal cellulase PcCel45A is reported, guided by the phase diagram. Nucleation and precipitation conditions were determined by sitting-drop vapor diffusion. Saturation and unsaturation conditions were evaluated by monitoring crystal dissolution, and a crystallization phase diagram was obtained. To obtain a large crystal, crystallization solution was prepared on a sitting bridge (diameter = 5?mm). Initial crystallization conditions were 40?µl of crystallization solution (40?mg?ml?1 protein with 30.5% 3-methyl-1,5-pentanediol in 50?mM tris-HCl pH 8.0) with a 1000?µl reservoir (61% 3-methyl-1,5,-pentanediol in 50?mM tris-HCl pH 8.0) at 293?K. After the first crystal appeared, the concentration of precipitant in the reservoir solution was reduced to 60% to prevent formation of further crystals. Finally, we obtained a crystal of 6?mm3 volume (3?mm × 2?mm × 1?mm), which was suitable for neutron diffraction.

Nakamura, Akihiko; Ishida, Takuya; Fushinobu, Shinya; Kusaka, Katsuhiro; Tanaka, Ichiro; Inaka, Koji; Higuchi, Yoshiki; Masaki, Mika; Ohta, Kazunori; Kaneko, Satoshi; Niimura, Nobuo; Igarashi, Kiyohiko; Samajima, Masahiro

2013-01-01

311

Family Literacy  

ERIC Educational Resources Information Center

Research indicates that family literacy programs can provide opportunities for educational success for parents and children. The benefits reaped by the children in family literacy workshops are presented.

Holloway, John H.

2004-01-01

312

Clinical features in a large Iranian family with a limb-girdle congenital myasthenic syndrome due to a mutation in DPAGT1  

PubMed Central

Mutations in DPAGT1 are a newly recognised cause of congenital myasthenic syndrome. DPAGT1 encodes an early component of the N-linked glycosylation pathway. Initially mutations in DPAGT1 have been associated with the onset of the severe multisystem disorder – congenital disorder of glycosylation type 1J. However, recently it was established that certain mutations in this gene can cause symptoms restricted to muscle weakness resulting from defective neuromuscular transmission. We report four cases from a large Iranian pedigree with prominent limb-girdle weakness and minimal craniobulbar symptoms who harbour a novel mutation in DPAGT1, c.652C>T, p.Arg218Trp. This myasthenic syndrome may mimic myopathic disorders and is likely under-diagnosed.

Basiri, Keivan; Belaya, Katsiaryna; Liu, Wei Wei; Maxwell, Susan; Sedghi, Maryam; Beeson, David

2013-01-01

313

Premutation for the Martin-Bell syndrome analyzed in a large Sardinian family: III. Molecular analysis with the StB12.3 probe  

SciTech Connect

This report complements a series of clinical, cytogenetical, and psychological studies previously reported on a large Sardinian pedigree segregating for premutations and full mutations associated with the Martin-Bell syndrome (MBS). Using the StB12.3 probe, we report now the molecular classification of all of the critical members of the pedigree. These molecular findings are evaluated against the variable phenotypic manifestations of the disease in the course of a six-generation segregation of an MBS premutation allegedly present in a common female progenitor of 14 MBS male patients and 9 female MBS heterozygotes seen in the last two generations. The nature and stepwise progression of MBS-premutations toward the fully manifested Martin-Bell syndrome and the possibility of reverse mutational events toward the normal allele are discussed with respect to the application of the presently available diagnostic tools in genetic counseling. 12 refs., 1 fig.

Grasso, M.; Perroni, L.; Dagna-Bricarelli, F. [Centro di Genetica Umana, Genova (Italy)] [and others

1996-08-09

314

A large-scale mutation search reveals genetic heterogeneity in 3M syndrome  

PubMed Central

The 3M syndrome is a rare autosomal recessive disorder recently ascribed to mutations in the CUL7 gene and characterized by severe pre- and postnatal growth retardation. Studying a series of 33 novel cases of 3M syndrome, we have identified deleterious CUL7 mutations in 23/33 patients, including 19 novel mutations and one paternal isodisomy of chromosome 6 encompassing a CUL7 mutation. Lack of mutations in 10/33 cases and exclusion of the CUL7 locus on chromosome 6p21.1 in six consanguineous families strongly support the genetic heterogeneity of the 3M syndrome.

Huber, Celine; Delezoide, Anee-Lise; Guimiot, Fabien; Baumann, Clarisse; Malan, Valerie; Le Merrer, Martine; Da Silva, Daniela Bezerra; Bonneau, Dominique; Chatelain, Pierre; Chu, Carol; Clark, Robin; Cox, Helen; Edery, Patrick; Edouard, Thomas; Fano, Virginia; Gibson, Kate; Gillessen-Kaesbach, Gabriele; Giovannucci-Uzielli, Maria-Luisa; Graul-Neumann, Luitgard Margarete; van Hagen, Johana-Maria; van Hest, Liselot; Horovitz, Dafne; Melki, Judith; Partsch, Carl-Joachim; Plauchu, Henry; Rajab, Anna; Rossi, Massimiliano; Sillence, David; Steichen-Gersdorf, Elisabeth; Stewart, Helen; Unger, Sheila; Zenker, Martin; Munnich, Arnold; Cormier-Daire, Valerie

2009-01-01

315

Family study of pediatric patients with primary antibody deficiencies.  

PubMed

Common variable immunodeficiency (CVID) and selective IgA deficiency (SIGAD) are the most common primary antibody deficiencies. These two diseases may have coincidence in one family and SIGAD can progress to CVID which suggest common underlying genetic defects between SIGAD and CVID. This study was designed to find the prevalence of multiple cases in families of Iranian patients with CVID or SIGAD.Serum samples were collected from all available first-degree relatives of 37 patients (23 patients with CVID and 14 with SIGAD) to check the levels of immunoglobulin and their subclasses and detect antibody deficiencies.First degree family members of 37 patients (106 individuals) were enrolled in this study. Thirty two percent of patients had multiple cases in their families. The frequency of primary antibody deficiency in the first relatives of the patients was estimated to be one per 9 family members. Most of the patients found among family members were siblings of the primary patients. Analysis in SIGAD family members showed that IgG and IgA levels in families with multiple cases were significantly lower than family members without multiple cases (p values of 0.048 and 0.021, respectively).Rate of families with multiple cases in Iran is more than the previous studies in other countries. This rate was not affected by the consanguinity of parents (p=0.081) or immunoglobulin level of the patients. Because of higher risk for the prevalence of these disorders in those with a positive family history of immunodeficiency, family screening programs in the patients with CVID and SIGAD can be suggested to be prioritized.. PMID:23996714

Rezaei, Nima; Abolhassani, Hassan; Kasraian, Amir; Mohammadinejad, Payam; Sadeghi, Bamdad; Aghamohammadi, Asghar

2013-08-28

316

Family Issues  

MedlinePLUS

... of families. Some have two parents, while others have a single parent. Sometimes there is no parent and grandparents raise grandchildren. Some children live in foster families, adoptive families, or in stepfamilies. Families are much more than groups of people who share the same genes or the same ...

317

[Family Involvement.  

ERIC Educational Resources Information Center

|This theme issue provides four articles that address family involvement in the transition of youth with disabilities from school to work. The first article, "Family Involvement" by Marge Goldberg and Shauna McDonald, offers evidence of the importance of family involvement at this stage of the individual's life, reports on families' experiences,…

Alliance: The Newsletter of the National Transition Alliance, 1996

1996-01-01

318

Histidinaemia in a consanguineous marriage  

PubMed Central

Support to the autosomal recessive inheritance for histidinaemia is given by the finding of an affected product from a first-cousin marriage. The histidine loading test done on the parents confirms previous reports that female heterozygous metabolize the amino acid at a slower rate than male heterozygous.

Rostenberg, I.; Guizar, J.; Alejandre, I.; Benitez, S.; Armendares, S.

1974-01-01

319

Family Day Care Licensing Study.  

ERIC Educational Resources Information Center

The 1990 Family Day Care Licensing Study provides the results of a nationwide survey of state regulatory agencies that was conducted to update family day care licensing information last collected in 1989. As in past years, the study includes an in-depth examination of regulatory requirements for large family day care homes. The study has been…

Children's Foundation, Washington, DC.

320

The mouse DNA binding protein Rc for the kappa B motif of transcription and for the V(D)J recombination signal sequences contains composite DNA-protein interaction domains and belongs to a new family of large transcriptional proteins  

SciTech Connect

Rc is a DNA binding protein with dual specificities for the V(D)J recombination signal sequences and for the B motif of the immunoglobulin kappa chain gene enhancer. The largest Rc transcript present in lymphoid cells/tissues is {approximately} 9 kb. Molecular cloning and sequence determination for 8822 bp of mouse Rc cDNA revealed an open reading frame of 2282 amino acids and long 5{prime}- and 3{prime}- untranslated regions. The derived amino acid sequence contains multiple DNA and protein interaction domains. Composite ZAS structures with tandem zinc fingers, and acidic motif, and a Ser/Thr-rich segment are located near the N-terminal and the C-terminal regions. The middle region of Rc contains a lone zinc finger, an acidic motif, a Ser-rich region, a nucleus localization signal, and GTPase motifs. Cloning and characterization of a mouse Rc gene show that the Rc cDNA corresponds to seven exons located in a genomic region spanning 70 kb. Exon 2 is exceptionally large, with 5487 bp. cDNA cloning and Northern blot analyses revealed multiple Rc transcripts, probably generated by alternative splicings. Sequence comparisons show that Rc belongs to a ZAS protein family that is involved in gene transcription and/or DNA recombination. The major histocompatibility complex class I gene enhancer binding proteins MBP1 and MBP2 are other representatives of this ZAS protein family. 43 refs., 6 figs., 2 tabs.

Wu, Lai-Chu; Liu, Yiling; Li, Zhiling [Ohio State Univ., Columbus, OH (United States)] [and others

1996-08-01

321

Fragile Families and Family Law  

Microsoft Academic Search

Family law reforms concerning paternity, child support, illegitimacy, and domestic violence have helped fragile families over the past 50 years. Yet fragile families remain invisible to much of family law because historically lawmakers have focused on the problems of the middle and upper classes. Also, the law still enshrines some confining stereotypes, thus encouraging the poor to enter into unstable,

LYNN D. WARDLE

322

Family Governance with Family Councils  

Microsoft Academic Search

From the third generation onwards, family firms could get into business threatening situations. This might depend on the growing number of owners, the increasing distance of family members from the firm, and the heterogeneity of their interests. Thus, agency prob- lems and negative conflicts might occur. This calls for the appropriate choice of family gov- ernance mechanisms. Family councils might

Klaus Brockhoff; Alexander Koeberle-Schmid

323

FAMILY STRUCTURE AND CHILD HEALTH OUTCOMES IN FRAGILE FAMILIES  

Microsoft Academic Search

Dramatic changes in family demography in the United States have led to increasing numbers of children living in “non-traditional” households. A large body of literature documents the association between living in a non-traditional family structure\\/familial instability and children’s cognitive and behavioral outcomes. In contrast, relatively little research has focused on the relationship between family structure and instability and children’s physical

Sharon Bzostek; Audrey Beck

2008-01-01

324

Lack of association of CYP1A1-MspI SNP and GSTM1 null genotypes with cancer in a Brazilian family with unusually high cancer incidence.  

PubMed

Research has shown that genetic polymorphisms in biotransformation enzymes, such as CYP1A1 and GSTM1, are related to a greater or lesser susceptibility to various cancers. We made an analysis of CYP1A1m1 SNP and GSTM1 null genotypes in a family group (71 members) related by consanguinity who had an unusually high incidence of cancer and a high frequency of smokers. There were no significant differences in genotype frequencies in this family when compared to data for Brazilian populations. Possibly, the high incidence of cancer in this sample is associated with smoking and/or other factors not detected in this survey. PMID:22782580

Moraes, L N; Borges, M F; Sousa, P A C; Venere, P C; Souza, I L

2012-06-15

325

A Novel non-sense Mutation in Keratin 10 Causes a Familial Case of Recessive Epidermolytic Ichthyosis  

PubMed Central

Epidermolytic ichthyosis (EI) is a rare skin disorder characterized by generalized erythroderma and cutaneous blistering at birth, which is substituted by hyperkeratosis later in life. It is caused by autosomal dominant mutations in highly conserved regions of KRT1 and KRT10. To date, only 4 mutations with autosomal recessive inheritance of EI have been described in consanguineous families. All of them affect the 2B domain of KRT10. In the present study we describe four patients with EI (including one lethal case) born from unaffected parents in a consanguineous family of a native Venezuelan community. The objective of this study was to characterize the clinical, genetic and morphological aspects of the disease in this family, as well as understand its functional implications. Genomic DNA was sequenced for KRT10 and KRT1. Immunofluoresence for keratin expression was performed on cutaneous biopsies. After examination of cutaneous biopsies histology, our results showed hyperkeratosis and acantholysis with an expanded granular layer. Sequencing of KRT10 demonstrated a non-sense mutation (p.Tyr282Ter.) corresponding to the 1B domain of the protein in patients and a heterozygous pattern in other family members, resulting in complete absence of K10. The loss of K10 was compensated by upregulation of K14 and K17. In conclusion, this novel mutation in KRT10 is the first recessive genetic variation that is not located in the so called “hot spot” for recessive EI, suggesting that other areas of the gene are also susceptible for such mutations.

Gutierrez, Jeydith A.; Hannoush, Zeina C.; Vargas, Luis G.; Momany, Allison; Garcia, Carmen C.; Murray, Jeffrey C.; Dunnwald, Martine

2013-01-01

326

Identification of two different mutations in the PDS gene in an inbred family with Pendred syndrome  

PubMed Central

Recently the gene responsible for Pendred syndrome (PDS) was isolated and several mutations in the PDS gene have been identified in Pendred patients. Here we report the occurrence of two different PDS mutations in an extended inbred Turkish family. The majority of patients in this family are homozygous for a splice site mutation (1143-2A?G) affecting the 3' splice site consensus sequence of intron 7. However, two affected sibs with non-consanguineous parents are compound heterozygotes for the splice site mutation and a missense mutation (1558T?G), substituting an evolutionarily conserved amino acid. The latter mutation has been found previously in two Pendred families originating from The Netherlands, indicating that the 1558T?G mutation may be a common mutation.???Keywords: PDS gene; Pendred syndrome

Coucke, P; Van Hauwe, P; Everett, L; Demirhan, O; Kabakkaya, Y; Dietrich, N; Smith, R; Coyle, E; Reardon, W; Trembath, R; Willems, P; Green, E; Van Camp, G

1999-01-01

327

Familial Aggregation of Blood Pressure  

Microsoft Academic Search

\\u000a In the first half of the last century, evidence for the familial aggregation of (elevated) blood pressure (BP) levels was\\u000a largely anecdotal and based on case reports of clinicians until a number of large family studies in the 1960s showed familial\\u000a resemblance of BP with correlations around 0.20 among first-degree relatives (1,2). Relatively few observations were made in children in

Xiaoling Wang; Harold Snieder

328

Family issues in child anxiety: Attachment, family functioning, parental rearing and beliefs  

Microsoft Academic Search

Family studies have found a large overlap between anxiety disorders in family members. In addition to genetic heritability, a range of family factors may also be involved in the intergenerational transmission of anxiety. Evidence for a relationship between family factors and childhood as well as parental anxiety is reviewed. Four groups of family variables are considered: (I) attachment; (II), aspects

Susan M. Bögels; Margaret L. Brechman-Toussaint

2006-01-01

329

Evidence for a Founder Mutation in the Cathepsin C Gene in Three Families with Papillon-Lef?vre Syndrome  

PubMed Central

Background Papillon-Lefèvre syndrome (PLS; OMIM 245000) is a rare autosomal recessive disorder. Clinically, PLS is characterized by hyperkeratosis involving the palms, soles, elbows and knees which is followed later on by periodontitis, destruction of alveolar bone and loss of primary and permanent teeth. The condition is caused by mutations in the cathepsin C (CTSC) gene. Methods We analyzed the DNA of members from 3 consanguineous families for mutations in the CTSC gene by direct sequencing analysis. We then performed haplotype analysis. Results We identified an identical recurrent missense mutation, R272P, in all 3 families. Microsatellite marker analysis around the CTSC gene revealed the same haplotype on the mutation-carrying allele in all 3 families. Conclusion The presence of this common mutation in families from 2 different geographical areas provides evidence for a founder effect for CTSC mutations in PLS.

Kurban, Mazen; Wajid, Muhammad; Shimomura, Yutaka; Bahhady, Ruba; Kibbi, Abdul-Ghani; Christiano, Angela M.

2009-01-01

330

Family Interactions in Adoptive Compared to Nonadoptive Families  

PubMed Central

Despite the large and growing numbers of adoptive families, little research describes interactions in families with adopted adolescents. Yet, adopted adolescents’ increased risk for adjustment problems, combined with the association between family interactions and adolescent adjustment in nonadoptive families, raises questions about differences in adoptive and nonadoptive family interactions. We compared observed and self-reported family interactions between 284 adoptive and 208 nonadoptive families and within 123 families with 1 adopted and 1 nonadopted adolescent. Adolescents averaged 14.9 years of age. Comparisons were made using analysis of variance incorporating hierarchical linear methods in SAS PROC MIXED to control family-related correlations in the data. Parents and children reported more conflict in adoptive families when compared with nonadoptive families. Families with 1 adopted and 1 nonadopted adolescent reported more conflict between parents and adopted adolescents. Observed parental behavior was similar across adoptive and nonadoptive children although adopted adolescents were less warm and, in families with 2 adopted children, more conflictual than nonadopted adolescents. These findings suggest a need for further investigation of the association between family interactions and adopted adolescent problem behavior.

Rueter, Martha A.; Keyes, Margaret A.; Iacono, William G.; McGue, Matt

2009-01-01

331

Molecular analysis reveals a high mutation frequency in the first untranslated exon of the PPOX gene and largely excludes variegate porphyria in a subset of clinically affected Afrikaner families.  

PubMed

A subset of probands from 11 South African families with clinical and/or biochemical features of variegate porphyria (VP), but without the known protoporphyrinogen oxidase (PPOX) gene defects identified previously in the South African population, were subjected to mutation analysis. Disease-related mutation(s) could not be identified after screening virtually the entire PPOX gene by heteroduplex single-strand conformation polymorphism analysis (HEX-SSCP), although three new sequence variants were detected in exon 1 of the gene in three normal controls. The presence of these single base changes at nucleotide positions 22 (C/G), 27 (C/A) and 127 (C/A), in addition to the known exon 1 polymorphisms I-26 and I-150, indicates that this untranslated region of the PPOX gene is particularly mutation-prone. Furthermore, microsatellite markers flanking the PPOX and alpha-1 antitrypsin (PI) gene, on chromosomes 1 and 14, respectively, were used to assess the probability of involvement of these loci in disease presentation. Common alleles transmitted from affected parent to affected child were determined where possible in the mutation-negative index cases. Allelic frequencies of these alleles were compared to findings in the normal population, but no predominant disease-associated allele could be identified. Co-segregation of a specific haplotype with the disease phenotype could also not be demonstrated in a large Afrikaner family. It is concluded that further studies are warranted to determine the genetic factor(s) underlying the autosomal dominant pattern of inheritance in molecularly uncharacterized cases showing clinical symptoms of an acute porphyria. PMID:9778454

Kotze, M J; De Villiers, J N; Groenewald, J Z; Rooney, R N; Loubser, O; Thiart, R; Oosthuizen, C J; van Niekerk, M M; Groenewald, I M; Retief, A E; Warnich, L

1998-10-01

332

A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum.  

PubMed

Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major genes for this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes. The phenotypic presentation in five patients was suggestive of a complex HSP that associated an early-onset spastic paraplegia with mild handicap, mental deterioration, congenital cataract, cerebellar signs, and TCC. The genome-wide search identified a single candidate region on chromosome 9, exceeding the LOD score threshold of +3. Fine mapping using additional markers narrowed the candidate region to a 45.1-Mb interval (15.4 cM). Mutations in three candidate genes were excluded. The mapping of a novel AR-HSP-TCC locus further demonstrates the extensive genetic heterogeneity of this condition. We propose that testing for this locus should be performed, after exclusion of mutations in SPG11 and SPG15 genes, in AR-HSP-TCC families, especially when cerebellar ataxia and cataract are present. PMID:20593214

Boukhris, Amir; Feki, Imed; Elleuch, Nizar; Miladi, Mohamed Imed; Boland-Augé, Anne; Truchetto, Jérémy; Mundwiller, Emeline; Jezequel, Nadia; Zelenika, Diana; Mhiri, Chokri; Brice, Alexis; Stevanin, Giovanni

2010-07-01

333

A novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid type.  

PubMed

The Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. Several genes have been implicated to result in EDS phenotypes. The progeroid type of EDS is characterized by wrinkled, loose skin on the face, curly fine hair, scanty eyebrows and eyelashes, in addition to the classical features of EDS. Here we describe two similarly affected individuals in two sibships of a large consanguineous family from Qatar. DNA samples from affected and unaffected members of the family were analyzed for homozygosity of polymorphic markers associated with genes that have been implicated in EDS. Among 28 markers analyzed, homozygosity was only observed for D5S469 and D5S2111, which were markers for galactosyltransferase-I (B4GALT7) located on chromosome 5q35.2, where the previously reported progeroid-like variant of EDS has been mapped. Exons harboring the coding regions and exon-intron junctions of B4GALT7 were amplified by PCR and examined for mutations. A homozygous misssense C to T substitution at nucleotide 808 in the coding region was discovered in both affected individuals. The carrier parents were heterozygous for this mutation, which was not found among 76 DNA samples from control individuals of the same ethnicity. Segregation of this novel mutation in the family further confirmed the allelic variant and its recessive mode of inheritance in this type of EDS. The C to T substitution results in an arginine to cysteine change at amino acid residue 270 that is located in the catalytically active extracellular C-terminal domain. This change could result in abnormal protein folding and/or aberrant interactions of mutated galactosyltransferase-I with other extracellular matrix proteins leading to the development of a progeroid-like phenotype in affected individuals. PMID:15211654

Faiyaz-Ul-Haque, Muhammad; Zaidi, Syed Hassan Ejaz; Al-Ali, Mariam; Al-Mureikhi, Mariam S; Kennedy, Shelley; Al-Thani, Ghalia; Tsui, Lap-Chee; Teebi, Ahmad Said

2004-07-01

334

America's Diverse Family Farms: Structure and Finances  

Microsoft Academic Search

American farms vary widely in size and other characteristics, but farming is still an industry of family businesses. Ninety-eight percent of farms are family farms, and they account for 86 percent of farm production. Very small farms are growing in number, and small family farms continue to own most farmland. But production is shifting toward very large family farms. Because

Robert A. Hoppe; James M. MacDonald; David E. Banker

2006-01-01

335

Family and childhood adjustment in cystic fibrosis  

Microsoft Academic Search

Family adaptation has been commonly associated with the psychological adjustment of chronically ill children. However, few studies have attempted to systematically evaluate this association and its relationship to illness severity. We studied 44 children ages 7 to 15 and their families at a large cystic fibrosis center and obtained measures of 1) impact of illness on the family; 2) family

Andres J. Pumariega; Deborah A. Pearson; Dan K. Seilheimer

1993-01-01

336

A new family programme in Zhejiang province.  

PubMed

Zhejiang Province in China has promoted a new family planning program since April 1993. The program stresses delayed marriage and childbearing, fewer and healthier births, modernization of family life, and prosperity through hard work. The people are receptive to the new program out of a desire for an improved standard of living. The objective is to build small, modern families who 1) practice deferred marriage and childbearing; 2) voluntarily practice family planning and have no unplanned births; 3) practice avoidance of consanguineous marriage, become sterilized if a carrier of a hereditary disease of chromosomal abnormality, and use premarital education and counseling and proper prenatal care; 4) uphold the laws and maintain discipline in action to avoid criminal behavior; 5) establish families that respect the old, care for children, and help their neighbors; 6) complete 9 years of compulsory education; and 7) create well being through hard work. The program is compatible with the strategy of the "three stresses" and an integrated approach. IEC and service provision are important components in program implementation. The target population are the masses and grassroots cadres, particularly those in the childbearing ages. IEC will be directed in different ways to different groups. Those aged 18-35 years will receive education. Face to face interaction with family planning workers and lectures will be directed to grassroots cadres. The mass media will be employed to reach the masses. The messages will include information and persuasion to adopt new families, accept family planning regulations, and learn about contraceptive use, healthy births and childrearing, education, health care, sex education, and income generation skills. Classes will be conducted for groups, such as teenagers, unmarried youth, pregnant women, and lactating women. Priority will be given to couples that accept the certificates for one child; favoritism will be granted for allocation of housing; acceptance in kindergartens and schools, employment, and military positions; and receipt of business licenses and poverty aide. Sterilization will be rewarded with longer paid leave and subsidies. Services will include contraceptive provision and follow-up, infertility treatment, gynecological check-ups, sex education, old age pensions, premarital counseling, and other quality services. PMID:12346835

Xu, B

1994-04-01

337

Family Treatment for Bipolar Disorder: Family Impairment by Treatment Interactions  

PubMed Central

Objective There is a clear need for psychosocial treatments to supplement pharmacotherapy for bipolar disorder. In this study, the efficacy of 2 forms of adjunctive family intervention were compared to pharmacotherapy alone. In addition to evaluating overall differences between treatments, a chief goal was to examine whether family impairment levels moderated the effects of family intervention on outcome. Method Ninety-two patients diagnosed with bipolar I disorder (according to DSM-III-R) were randomly assigned to receive (1) pharmacotherapy alone, (2) family therapy + pharmacotherapy, or (3) multi-family psychoeducational group + pharmacotherapy. Treatments and assessments continued for up to 28 months. Primary outcome measures were number of episodes per year and percentage of time symptomatic throughout the entire follow-up period. The study was conducted from September 1992 through March 1999. Results No significant main effects were found for treatment condition. Thus, for the total sample, the addition of a family intervention did not improve outcome. However, there were significant treatment condition by family impairment interactions (p < .05). In patients from families with high levels of impairment, the addition of a family intervention (family therapy or psychoeducational group) resulted in a significantly improved course of illness, particularly the number of depressive episodes (p <.01) and proportion of time spent in a depressive episode (p <.01). These effects were relatively large (Cohen d = 0.7–1.0), with patients receiving either family intervention having roughly half the number of depressive episodes and amount of time spent depressed as those receiving pharmacotherapy alone. In contrast, for patients from low-impairment families, the addition of a family intervention did not improve course of illness. Conclusions Our findings build on previous literature suggesting the importance of treatment matching within the mood disorders and suggest that the utility of adding family interventions for bipolar patients and their families may depend upon the family’s level of impairment.

Miller, Ivan W.; Keitner, Gabor I.; Ryan, Christine E.; Uebelacker, Lisa A.; Johnson, Sheri L.; Solomon, David A.

2010-01-01

338

Family welfare programme.  

PubMed

Tamil Nadu is the first Indian State to recognize the basic relevance of family planning to national planning. It was given national awards for outstanding work in family planning for every year except 1964 from 1961 to 1967, and from 1973 to 1976. Family planning activity was initiated in large maternity hospitals as a postpartum program. The Medical Termination of Pregnancy Act was first implemented in Tamil Nadu. 141 institutions have been certified for the operation. An oral pill program is being implemented in all the rural and urban family welfare centers including the hospitals. The family welfare program has been fully integrated with the Maternal and Child Health (MCH) program which has created confidence among people that their children will be protected from health hazards. The MCH Schemes are conducted through primary health care (PHC) centers, urban family welfare centers, MCH centers, hospitals, and dispensaries. Dais are trained to improve the techniques of midwifery and aid delivery in a hygienic manner. Dais can also use their influence in the local community to further family planning. It is proposed to establish additional subcenters in selected districts to average 1/center/5000 population. The government continues to sponsor and fund equipment, facilities, and infrastructure to facilitate sterilization operations in primary health centers. PMID:12262521

Namadevan, V

1980-07-01

339

Family Reunification  

ERIC Educational Resources Information Center

|Reunifying children placed in foster care with their birth parents is a primary goal of the child welfare system. Yet, relatively little is known about the reunification process. This article analyzes new data on trends in family reunification and discovers: (1) Although most children still exit foster care through family reunification, exit…

Wulczyn, Fred

2004-01-01

340

Familial severe congenital diaphragmatic hernia: left herniation in one sibling and bilateral herniation in another.  

PubMed

Familial congenital diaphragmatic hernia (CDH) is extremely rare; it comprises about 2% of all CDH cases. The empirical risk is about 2%, increasing to 10% in a family with two affected children. This report describes severe CDH in two siblings who had been diagnosed prenatally. The female newborn diagnosed with left CDH prenatally was born at 38 weeks of gestation. Despite surgical repair and intensive treatment, she died 10 days after birth. Her younger brother was born at 39 weeks of gestation after being diagnosed with bilateral CDH prenatally, and died 75 min after birth. Both infants had neither other congenital anomaly nor chromosomal abnormalities. Their parents are healthy without consanguinity. Their first daughter and the fourth child have no congenital anomalies. PMID:23480359

Nagase, Hiromi; Ishikawa, Hiroshi; Kurosawa, Kenji; Furuya, Noritaka; Itani, Yasufumi; Yamanaka, Michiko

2013-03-01

341

A Family of Adders  

Microsoft Academic Search

Binary c arry-propagating addition can be efficiently expressed a s a prefix computation. Several examples of adders based on such a formulation have been published, and efficient implementations are numerous. Chief among the k nown constructions are those of Kogge & Stone and Ladner & Fischer. In this work we show that these are end cases of a large family

Simon Knowles

1999-01-01

342

A Family of Adders  

Microsoft Academic Search

Binary carry-propagating addition can be efficiently expressed as a prefix computation. Several examples of adders based on such a formulation have been published and efficient implementations are numerous. Chief among the known constructions are those of Kogge and Stone (1973) and Ladner and Fischer (1980). In this work we show that these are end cases of a large family of

Simon Knowles

2001-01-01

343

Asian Family Planning  

Microsoft Academic Search

Rapid population growth in the Third World has been accompanied by the creation of national family planning programs, which attempt to slow growth rates through programs aimed at the prevention of births. These programs represent large scale, modern bureaucratic health delivery systems that are transplanted from the industrialized world. They raise the problem of whether such modern organizations can have

Gayl D. Ness; Karl R. Landis

1987-01-01

344

Family acholeplasmataceae (including phytoplasmas)  

Technology Transfer Automated Retrieval System (TEKTRAN)

The family Acholeplasmataceae was originally established to accommodate the genus Acholeplasma, comprising the mollicutes that could be cultivated without the supplement of cholesterol and that use UGA as a stop codon instead of coding for tryptophan. It was later shown that the phytoplasmas, a larg...

345

Family Theory and Family Health Research  

PubMed Central

Different family theories can be applied to different aspects of how families experience health and illness. The family health and illness cycle describes the phases of a family's experience, beginning with health promotion and risk reduction, then family vulnerability and disease onset or relapse, family illness appraisal, family acute response, and finally family adaptation to illness and recovery. For each phase, specific family theories that are most appropriate for guiding family and health research are discussed.

Doherty, William J.

1991-01-01

346

Familial abdominal aortic aneurysms: Collection of 233 multiplex families  

Microsoft Academic Search

Objective: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband. Subjects and Methods: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom

Helena Kuivaniemi; Hidenori Shibamura; Claudette Arthur; Ramon Berguer; C. William Cole; Tatu Juvonen; Ronald A. Kline; Raymond Limet; Gerry MacKean; Örjan Norrgård; Gerard Pals; Janet T. Powell; Pekka Rainio; Natzi Sakalihasan; Clarissa van Vlijmen-van Keulen; Alain Verloes; Gerard Tromp

2003-01-01

347

Familial segregation of cervical ribs, Sprengel anomaly, preaxial polydactyly, anal atresia, and urethral obstruction: a new syndrome?  

PubMed

In a consanguineous Jewish family originating from Bombay, India, the propositus presented with anal atresia, micropenis, urethral obstruction with secondary prune belly, omphalocele, patent urachus, and cryptorchidism. The kidneys were dysplastic and he had the Potter phenotype with limb deformities. Additional findings included IUGR with microcephaly, congenital heart defects, spinal anomalies, and hypoplastic lungs. The mother and all three sisters had cervical ribs, and she and one sister had 11 pairs of thoracic ribs. The other two sisters had chronic immune thrombopenia. One of those had bilateral Sprengel deformity with homovertebral bones, club feet, and microcephaly and the other sister also had unilateral preaxial hexadactyly. Although familial segregation of cervical ribs and Sprengel deformity has been reported, the association of the findings in this family is unique and may represent a new syndrome. X-linked dominant transmission may explain the severe manifestations in the affected male, but other modes of inheritance may also apply. PMID:8456850

Frydman, M; Cohen, H A; Ashkenazi, A; Varsano, I

1993-03-15

348

[Family ideology].  

PubMed

This paper treats the definition of the concept of family ideology linking it to that of social ideology. In both cases the ideology is seen as patterns of messages that obey certain semantic rules. Within the family context, it is considered that the conditions of production of the ideology are, concerning the profound structures, the unconscious oedipus conflict and kindred system that determines the family organization. Concerning the surface structures, the myths and beliefs that appear in each group as an answer to the need of accounting for the conflicts inherent to the family structure. The family ideology guides the subjects to places predetermined by the oedipus conflicts, "semanticizes" the conflicts and tends to dissimulate the conditions of production through the illusion that the subject is the producer. To analyze the family ideology, the following items must be taken into account: 1) Which are the semantic lines that are privileged in the couple and parent-children relationships. 2) The relations between the semantic lines established by the articulation rules prescribed by the cultural system. 3) The elementary forms of the ideological universe (the "actantial" model applied to family relationships). These three aspects articulate between themselves through transformation rules. PMID:7136827

Kornblit, A

1982-06-01

349

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (The Health Family Tree Study and the NHLBI Family Heart Study)  

Microsoft Academic Search

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family

Roger R Williams; Steven C Hunt; Gerardo Heiss; Michael A Province; Jeannette T Bensen; Millicent Higgins; Robert M Chamberlain; Joan Ware; Paul N Hopkins

2001-01-01

350

Family Therapy  

MedlinePLUS

... your son or other family members erupt into arguments and you're left feeling frustrated and angry. ... Your e-mail Clicking "send" signifies that you have read and agree to our privacy policy. Share ...

351

Family Issues  

MedlinePLUS

... the challenges of autism and provides a safe, inclusive environment for both the child and family (see ... the lives of all affected by autism through education, advocacy, services, research and support.

352

Family Life  

MedlinePLUS

... partner and feel sad and frustrated by your limitations. Both people in your relationship may benefit from ... friends, family members, or professionals. Talking openly about limitations and brainstorming possible solutions will help both of ...

353

Family History  

MedlinePLUS

... found at http://www.usa.gov . Public Health Genomics Genomics About Us Weekly Update Genomics and Health Family Health History Genomic Testing EGAPP Implementation Reports and Publications Blog Podcasts ...

354

Importance of Family Routines  

MedlinePLUS

... Life > Family Dynamics > The Importance of Family Routines Family Life Listen The Importance of Family Routines Article Body Why are family routines so important to children? Every family needs ...

355

Normal Functioning Family  

MedlinePLUS

... Children > Family Life > Family Dynamics > Normal Functioning Family Family Life Listen Normal Functioning Family Article Body Is there any way to tell if my family is functioning normally? Many parents ask themselves this ...

356

Teaching Family Therapy: Ten Key Questions for Understanding the Family as Patient.  

ERIC Educational Resources Information Center

Ten questions for understanding the family as patient are presented as one aspect of an overall teaching plan for family therapy. Seeing the family as patient is important in initial stages of evaluation and therapy. A case study of a large, overly close family is used as an illustration. (Author)

Resnikoff, Roy O.

1981-01-01

357

Veritas Asteroid Family Still Holds Secrets?  

NASA Astrophysics Data System (ADS)

Veritas asteroid family has been studied for about two decades. These studies have revealed many secrets, and a respectable knowledge about this family had been collected. Here I will present many of these results and review the current knowledge about the family. However, despite being extensively studied, Veritas family is still a mystery. This will be illustrated through the presentation of the most interesting open problems. Was there a secondary collision within this family? Does asteroid (490) Veritas belong to the family named after it? How large was the parent body of the family? Finally, some possible directions for future studies that aims to address these questions are discussed as well.

Novakovic, B.

2012-12-01

358

[Family therapy in polygamous families].  

PubMed

Patients from polygamous families are over-represented in the Enugu Psychiatric Hospital. The authors came to this conclusion after case notes from 116 anxiety neurotic, 101 schizophrenic and 117 depressive patients were examined. The patients were treated from 1970 to 1979. Polygamy was shortly described with its advantages and disadvantages. Competition between the wives, over-burdening of the husband and often poor care of the children represent the background for the symptoms of the patients, who come from such families. Looking for useful therapeutic methods the method of the natives to solve family quarrels were viewed. Making use of psychoanalytic therapy models especially as represented by Dührssen, Richter and Toman a family therapy model was presented which takes the native judgement model into consideration. A case was presented to illustrate the above. PMID:7234152

Ebigho, P O; Onyeama, W P; Ihezue, U H; Ahanotu, A C

359

Homolog of the polymorphic 4q35 FSHD locus (p13E-11; D4F104S1) maps to 10qter; exclusion as a second FSHD locus in a large Danish family  

SciTech Connect

Facioscapulohumeral muscular dystrophy (FSHD) has been mapped to 4q35 and shown to be associated with deletions that are detectable using probe p13E-11 (D4104S1). These deletions reside within highly polymorphic restriction fragments (20-300 kb) which can normally only be resolved completely using pulsed-field gel electrophoresis (PFGE). Family studies showed that p13E-11 detects two non-allelic loci, only one of which originates from 4q35 origin. In 20 CEPH families, 8 individuals were identified showing a `small` EcoRI fragment detectable by conventional Southern blotting. Linkage analysis allowed assignment of these fragments to 10qter (D10S212 and D10S180) in all families tested. Since FSHD shows genetic heterogeneity, this second p13E-11 locus on 10qter became an interesting candidate as a second FSHD family did not provide evidence for linkage on chromosome 10qter.

Frants, R.R.; Bakker, E.; Vossen, R.H.A.M. [and others

1994-09-01

360

Familial nonsyndromic pheochromocytoma.  

PubMed

Judging from recent data, heritable forms account for 30-40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon-intron boundaries included). The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5-cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family. The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2+43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes. PMID:17102081

Opocher, Giuseppe; Schiavi, Francesca; Iacobone, Maurizio; Toniato, Antonio; Sattarova, Sabina; Erlic, Zoran; Martella, Maddalena; Mian, Caterina; Merante Boschin, Isabella; Zambonin, Laura; De Lazzari, Paola; Murgia, Alessandra; Pelizzo, Maria Rosa; Favia, Gennaro; Mantero, Franco

2006-08-01

361

Family Structure, Materialism, and Compulsive Consumption  

Microsoft Academic Search

Despite the rapid and dramatic changes in the structure of the American family over the past thirty years (e.g., divorce, single parenting), consumer researchers have largely neglected the issue of how alternative family forms influence consumer behavior. The authors' initial inquiry into this area finds that young adults reared in disrupted families are more materialistic and exhibit higher levels of

Aric Rindfleisch; James E. Burroughs; Frank Denton

1997-01-01

362

Familial parkinsonism: Our experience and review  

Microsoft Academic Search

There is substantial interest in the possible role of genetic factors in the etiology of idiopathic parkinsonism (IP) and parkinsonism-plus syndromes (PPS). We have longitudinally investigated eight large kindreds from North America. Five families demonstrated IP features, two families represented PPS and in one family, neither a diagnosis of IP or PPS could be established. A literature review supported our

Melody A. Denson; Zbigniew K. Wszolek

1995-01-01

363

Family Child Care Licensing Study, 2002.  

ERIC Educational Resources Information Center

|This report presents the findings of the 2002 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2001 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Children's Foundation, Washington, DC.

364

Family Child Care Licensing Study, 2001.  

ERIC Educational Resources Information Center

|This report presents the findings of the 2001 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2000 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Children's Foundation, Washington, DC.

365

Family Child Care Licensing Study, 2003.  

ERIC Educational Resources Information Center

|This report presents the findings of the 2003 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2002 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Hollestelle, Kay; Koch, Pauline D.

366

Family Child Care Licensing Study, 2000.  

ERIC Educational Resources Information Center

|This report presents the findings of the 2000 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1999 study. Data on small family child care homes and group or large family child care homes are organized in 23 categories: (1) number of regulated homes; (2)…

Kelly, Nia, Comp.

367

The Family Child Care Licensing Study, 1999.  

ERIC Educational Resources Information Center

|This report presents the findings of the 1999 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1998 study. Data on small family child care homes and group or large family child care homes are organized in 22 categories: (1) number of regulated homes; (2)…

Children's Foundation, Washington, DC.

368

Conservatism and monitoring by founding family owners  

Microsoft Academic Search

We study the role of conservatism in monitoring managers by founding family owners, the most predominant type of large, under-diversified shareholders in the U.S. We focus on the ownership of founding family members who are not CEOs. Unlike owners with diverse ownership or institutional investors, family owners have both the incentives and the means to monitor CEOs. While conservatism can

Shuping Chen; Xia Chen; Qiang Cheng; Amy Hutton

369

Family Foundations  

Microsoft Academic Search

A new program in California partners the California Department of Corrections with a non-profit drug treatment agency on behalf of pregnant or parenting women who are drug offenders with substance abuse histories. The women are sentenced to the family foundations facility for one year and receive a range of special services to prepare for community re-entry. This paper provides a

Brenda Wiewel; Toni Mosley

2006-01-01

370

Family Hypnotherapy.  

ERIC Educational Resources Information Center

A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

Araoz, Daniel L.; Negley-Parker, Esther

1985-01-01

371

Familial dysautonomia  

Microsoft Academic Search

Familial dysautonomia is a developmental disorder of the sensory and autonomic nervous system. Recent studies have shown that two mutations in the gene IKBKAP are responsible for the disease. IKAP, the IKBKAP-encoded protein, is a member of the recently identified human Elongator complex. The major FD mutation is a splice mutation that results in aberrant tissue-specific mRNA splicing.

Susan A Slaugenhaupt; James F Gusella

2002-01-01

372

Family Letters  

Microsoft Academic Search

:Falbel describes the process by which she and her brother and parents were saved from Austria on the eve of WWII through the determined efforts of an aunt and uncle in America, and subsequent failed attempts to obtain exit visas for her grandparents. Included are seven letters from among hundreds that were sent between family members in different countries, describing

Rita Falbel

2009-01-01

373

Family Letters  

Microsoft Academic Search

Falbel describes the process by which she and her brother and parents were saved from Austria on the eve of WWII through the determined efforts of an aunt and uncle in America, and subsequent failed attempts to obtain exit visas for her grandparents. Included are seven letters from among hundreds that were sent between family members in different countries, describing

Translated

2009-01-01

374

Family Violence.  

ERIC Educational Resources Information Center

|This quarterly publication, issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), contains articles dealing with family violence and alcohol abuse, children of alcoholic parents, training programs for counselors, and confidentiality of client records. The three articles on alcohol abuse suggest that: (1) there is a clear…

Sorgen, Carol, Ed.

1979-01-01

375

My Family.  

ERIC Educational Resources Information Center

|This elementary reader is designed for use in a bilingual Inupiat-English program in Buckland and Deering, Alaska. It is the story of a small boy named Paul and his family. The Inupiat text and its English equivalent are never in opposition. The Inupiat text is presented on a picture page, with the English on the back. The illustrations, by J.…

Alaska State-Operated Schools, Anchorage.

376

Family Structure and Family Processes in Mexican American Families  

PubMed Central

Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct, CD/ODD and MDD symptoms, and greater parent-child conflict than their counterparts in two parent families. Single parent mothers reported greater economic hardship, depression and family stress. Family stress and parent-child conflict emerged as significant mediators of the association between family structure and early adolescent outcomes, suggesting important processes linking MA single parent families and adolescent adjustment.

Zeiders, Katharine H.; Roosa, Mark W.; Tein, Jenn-Yun

2010-01-01

377

Hydrops fetalis and early neonatal multiple organ failure in familial hemophagocytic lymphohistiocytosis.  

PubMed

Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetic heterogeneous autosomal recessive disorder. We report two siblings with FHLH caused by a PRF1 mutation. The first child died in utero with hydrops fetalis and the second presented soon after birth with fatal multiple organ failure. Post-mortem DNA analysis showed a homozygous c.666C>A (p.His222Gln) mutation in the PRF1 gene in both cases, with their non-consanguineous parents being heterozygous for the same mutation. Review of the literature shows that perinatal presentation of FHLH is rare. Diagnosis is difficult because in most cases histologic examination reveals no hemophagocytosis and the disease is rapidly fatal. The association between hydrops fetalis and FHLH has been reported in four previous reports. We present the first case of hydrops fetalis caused by FHLH, confirmed by DNA analysis. FHLH should be included in the differential diagnosis of non-immune hydrops fetalis and neonatal multiple organ failure. PMID:19595804

Vermeulen, Marijn J; de Haas, Valerie; Mulder, Margot F; Flohil, Claudie; Fetter, Willem P F; van de Kamp, Jiddeke M

2009-07-10

378

Primary hypogonadism, partial alopecia, and Mullerian hypoplasia: report of a third family and review.  

PubMed

Two sisters presented with partial alopecia, primary hypergonadotropic hypogonadism and Mullerian hypoplasia associated with mild mental retardation, microcephaly, flat occiput, sparse eyebrows, absence of breast tissue, absent ovaries, mild-moderate dorsal kyphosis, thin upper lip and unilateral sensorioneural deafness in one of them. They were the product of a Turkish consanguineous marriage. The clinical course for our patients is similar to two families reported by Al-Awadi et al. [Al-Awadi et al. (1985) Am J Med Genet 22:619-622] and Megarbane et al. [Megarbane et al. (2003) Am J Med Genet Part A 119A:214-217]. This report supports the literature by proposing an autosomal recessive syndrome which was firstly reported by Al-Awadi et al. [Al-Awadi et al. (1985) Am J Med Genet 22:619-622]. This condition may be due to a founder mutation. PMID:19213036

Tatar, Abdulgani; Ocak, Zeynep; Tatar, Arzu; Yesilyurt, Ahmet; Borekci, Bunyamin; Oztas, Sitki

2009-03-01

379

Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping  

SciTech Connect

Homozygosity mapping is a powerful strategy for mapping rare recessive traits in children of consanguineous marriages. Practical applications of this strategy are currently limited by the inability of conventional linkage analysis software to compute, in reasonable time, multipoint LOD scores for pedigrees with inbreeding loops. We have developed a new algorithm for rapid multipoint likelihood calculations in small pedigrees, including those with inbreeding loops. The running time of the algorithm grows, at most, linearly with the number of loci considered simultaneously. The running time is not sensitive to the presence of inbreeding loops, missing genotype information, and highly polymorphic loci. We have incorporated this algorithm into a software package, MAPMAKER/HOMOZ, that allows very rapid multipoint mapping of disease genes in nuclear families, including homozygosity mapping. Multipoint analysis with dozens of markers can be carried out in minutes on a personal workstation. 23 refs., 4 figs., 1 tab.

Kruglyak, L.; Daly, M.J. [Whitehead Institute for Biomedical Research, Cambridge, MA (United States); Lander, E.S. [Whitehead Institute for Biomedical Research, Cambridge, MA (United States)]|[Massachusetts Institute of Technology, Cambridge, MA (United States)

1995-02-01

380

A novel heterozygous deletion–insertion mutation (2695–2712 del\\/GTTTGT ins) in exon 18 of the filamin C gene causes filaminopathy in a large Chinese family  

Microsoft Academic Search

Filaminopathy represents a rare subgroup of myofibrillar myopathies caused by mutation in filamin C gene. We present a Chinese family with filaminopathy, characterized by onset at the age of 35–40years with progressive muscle weakness in all limbs. Mild cardiac symptoms and chronic diarrhea were present in a few patients. Muscle biopsy revealed numerous spheroid bodies and amorphous deposits in the

Xinghua Luan; Daojun Hong; Wei Zhang; Zhaoxia Wang; Yun Yuan

2010-01-01

381

A Lebanese family with autosomal recessive oculo-auriculo-vertebral (OAV) spectrum and review of the literature: is OAV a genetically heterogeneous disorder?  

PubMed Central

Oculo-auriculo-vertebral (OAV) spectrum summarizes a continuum of ocular, auricular, and vertebral anomalies. Goldenhar syndrome is a variant of this spectrum and is characterized by pre-auricular skin tags, microtia, facial asymmetry, ocular abnormalities, and vertebral anomalies of different sizes and shapes. Most cases are thought to be sporadic. However, a few families were reported to have an autosomal recessive inheritance and other families’ presentation of the syndrome strongly supported an autosomal dominant inheritance. We report OAV in a female infant presenting with tracheomalacia, diaphragmatic hernia, encephalomeningocele, sacral neural tube defect, and cardiac defect and her brother having no more than dysmorphic features. The mode of inheritance in this family supports an autosomal recessive inheritance where the transmission was from normal first-degree consanguineous parents to one of the sons and to the daughter. This report further broadens the clinical presentation and symptoms of OAV and supports the hypothesis advancing OAV as a genetically heterogeneous disorder.

Farra, Chantal; Yunis, Khaled; Yazbeck, Nadine; Majdalani, Marianne; Charafeddine, Lama; Wakim, Rima; Awwad, Johnny

2011-01-01

382

Familiality of female and male homosexuality  

Microsoft Academic Search

We examined data from a large cohort of homosexual and heterosexual females and males concerning their siblings' sexual orientations. As in previous studies, both male and female homosexuality were familial. Homosexual females had an excess of homosexual brothers compared to heteroxual subjects, thus providing evidence that similar familial factors influence both male and female homosexuality. Furthermore, despite the large sample

J. Michael Bailey; Alan P. Bell

1993-01-01

383

Familial mesothelioma: a report of two families  

Microsoft Academic Search

Five reports of familial mesothelioma in which mesotheliomas occurred in two or more family members have been recorded in the medical literature. In this report, we describe two examples of familial mesothelioma. In one family, three brothers who worked in the asbestos insulation industry developed mesothelioma. In the second family, the father, who was occupationally exposed to asbestos, died from

Samuel P. Hammar; Dawn Bockus; Franque Remington; Susan Freidman; Gordon LaZerte

1989-01-01

384

Large = 4 holography  

NASA Astrophysics Data System (ADS)

The class of 2d minimal model CFTs with higher spin AdS3 duals is extended to theories with large = 4 superconformal symmetry. We construct a higher spin theory based on the global D(2 , 1 |?) superalgebra, and propose a large N family of cosets as a dual CFT description. We also indicate how a non-abelian version of this Vasiliev higher spin theory might give an alternative description of IIB string theory on an AdS3 × S3 × S3 × S1 background.

Gaberdiel, Matthias R.; Gopakumar, Rajesh

2013-09-01

385

Military Families Considering Adoption  

MedlinePLUS

... Centered Casework Practice Family Group Decision-Making Engaging Communities to Support Families Creating a Family-Centered Agency Culture Child Abuse & Neglect Child Abuse & Neglect Home Overview ...

386

Family Support Program  

MedlinePLUS

... Families : Family Support Printer Friendly Send to friend Family Support Program If a child you love has ... launched our scholarship program in 2002 to assist families devastated by the cost of medical care to ...

387

Large intestine  

NSDL National Science Digital Library

The large intestine is larger and shorter than the small intestine and connects to the small intestine and the anus. Nutrient deficient material from the small intestine travels through the large intestine to the anus. This material is called feces and is excreted. Feces is made up of material that our bodies cannot break down into smaller parts to be used by the body.

Katie Hale (CSUF;)

2007-08-18

388

Reclaiming Family Privilege  

ERIC Educational Resources Information Center

|The pull for family is strong, almost primeval, most likely it is evolutionary, and for those lacking the benefit of family or Family Privilege, the loss of family is painful and profoundly sad. Young people who struggle to cope without stable family connections are profoundly aware of their lack of "Family Privilege." In this article, the author…

Seita, John

2012-01-01

389

Co-occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers.  

PubMed

Disorders within the "ciliopathy" spectrum include Joubert (JS), Bardet-Biedl syndromes (BBS), and nephronophthisis (NPHP). Although mutations in single ciliopathy genes can lead to these different syndromes between families, there have been no reports of phenotypic discordance within a single family. We report on two consanguineous families with discordant ciliopathies in sibling. In Ciliopathy-672, the older child displayed dialysis-dependent NPHP whereas the younger displayed the pathognomonic molar tooth MRI sign (MTS) of JS. A second branch displayed two additional children with NPHP. In Ciliopathy-1491, the oldest child displayed classical features of BBS whereas the two younger children displayed the MTS. Importantly, the children with BBS and NPHP lacked MTS, whereas children with JS lacked obesity or NPHP, and the child with BBS lacked MTS and NPHP. Features common to all three disorders included intellectual disability, postaxial polydactyly, and visual reduction. The variable phenotypic expressivity in this family suggests that genetic modifiers may determine specific clinical features within the ciliopathy spectrum. PMID:22002901

Zaki, Maha S; Sattar, Shifteh; Massoudi, Rustin A; Gleeson, Joseph G

2011-10-14

390

Co-occurrence of Distinct Ciliopathy Diseases in Single Families Suggests Genetic Modifiers  

PubMed Central

Disorders within the “ciliopathy” spectrum include Joubert (JS), Bardet–Biedl syndromes (BBS), and nephronophthisis (NPHP). Although mutations in single ciliopathy genes can lead to these different syndromes between families, there have been no reports of phenotypic discordance within a single family. We report on two consanguineous families with discordant ciliopathies in sibling. In Ciliopathy-672, the older child displayed dialysis-dependent NPHP whereas the younger displayed the pathognomonic molar tooth MRI sign (MTS) of JS. A second branch displayed two additional children with NPHP. In Ciliopathy-1491, the oldest child displayed classical features of BBS whereas the two younger children displayed the MTS. Importantly, the children with BBS and NPHP lacked MTS, whereas children with JS lacked obesity or NPHP, and the child with BBS lacked MTS and NPHP. Features common to all three disorders included intellectual disability, postaxial polydactyly, and visual reduction. The variable phenotypic expressivity in this family suggests that genetic modifiers may determine specific clinical features within the ciliopathy spectrum. © 2011 Wiley Periodicals, Inc.

Zaki, Maha S; Sattar, Shifteh; Massoudi, Rustin A; Gleeson, Joseph G

2011-01-01

391

Family ownership and the cost of under-diversification  

Microsoft Academic Search

We argue that the cost to a family of holding a large block of shares in a company, or under-diversifying, is reflected in the diversification benefits that the family forfeits. These costs can be substantial. For example, given a constant relative risk aversion parameter of 2, the median cost to our sample of families controlling large Swedish firms is 13%

Richard Heaney; Martin Holmen

2008-01-01

392

Reanalysis of asteroid families structure through visible spectroscopy  

Microsoft Academic Search

The taxonomic properties of the main asteroid families are analyzed and discussed in the light of an updated definition of the families using a large proper elements database and the asteroids taxonomy derived from reflectance spectra recently obtained by two large visible spectroscopic surveys: the SMASS II and the S3OS2. Our analysis indicates that most families are quite homogeneous taxonomically

T. Mothé-Diniz; F. Roig; J. M. Carvano

2005-01-01

393

The laminin family.  

PubMed

Laminins are large molecular weight glycoproteins constituted by the assembly of three disulfide-linked polypeptides, the ?, ? and ? chains. The human genome encodes 11 genetically distinct laminin chains. Structurally, laminin chains differ by the number, size and organization of a few constitutive domains, endowing the various members of the laminin family with common and unique important functions. In particular, laminins are indispensable building blocks for cellular networks physically bridging the intracellular and extracellular compartments and relaying signals critical for cellular behavior, and for extracellular polymers determining the architecture and the physiology of basement membranes. PMID:23263632

Aumailley, Monique

2012-12-21

394

Non-family-members in the family business management team: a multinational investigation  

Microsoft Academic Search

The purpose of this study was to investigate, in a multi-country context, the inclusion of family-member managers and non-family-member\\u000a managers in family businesses, and the relationship of this variable to certain management activities, styles and characteristics.\\u000a A large sample (N = 593) of family businesses was generated from six countries (Croatia, Egypt, France, India, Kuwait and the United States),\\u000a countries

Matthew C. Sonfield; Robert N. Lussier

2009-01-01

395

Effects of family connection and family individuation  

Microsoft Academic Search

This prospective longitudinal study explores the differential effects of family connection and family individuation measured during adolescence on later midlife well-being. Home interviews were held in the 1970s with 99 families of 245 adolescents. Connection and individuation in the family system were measured by self-report, a projective exercise, and coding of taped family interactions. Twenty-five years later, telephone interviews were

Linda G. Bell; David C. Bell

2009-01-01

396

Segregation of a Latent High Adiposity Phenotype in Families with a History of Type 2 Diabetes Mellitus Implicates Rare Obesity-Susceptibility Genetic Variants with Large Effects in Diabetes-Related Obesity  

PubMed Central

Background We recently reported significantly greater weight gain in non-diabetic healthy subjects with a 1st degree family history (FH+) of type 2 diabetes mellitus (T2DM) than in a matched control group without such history (FH?) during voluntary overfeeding, implying co-inheritance of susceptibilities to T2DM and obesity. We have estimated the extent and mode of inheritance of susceptibility to increased adiposity in FH+. Methods Normoglycaemic participants were categorised either FH+ (?1 1st degree relative with T2DM, 50F/30M, age 45±14 (SD) yr) or FH? (71F/51M, age 43±14 yr). Log-transformed anthropometric measurements (height, hip and waist circumferences) and lean, bone and fat mass (Dual Energy X-ray Absorptiometry) data were analysed by rotated Factor Analysis. The age- and gender-adjusted distributions of indices of adiposity in FH+ were assessed by fits to a bimodal model and by relative risk ratios (RR, FH+/FH?) and interpreted in a purely genetic model of FH effects. Results The two orthogonal factors extracted, interpretable as Frame and Adiposity accounted for 80% of the variance in the input data. FH+ was associated with significantly higher Adiposity scores (p<0.01) without affecting Frame scores. Adiposity scores in FH+ conformed to a bimodal normal distribution, consistent with dominant expression of major susceptibility genes with 59% (95% CI 40%, 74%) of individuals under the higher mode. Calculated risk allele frequencies were 0.09 (0.02, 0.23) in FH?, 0.36 (0.22, 0.48) in FH+ and 0.62 (0.36, 0.88) in unobserved T2DM-affected family members. Conclusions The segregation of Adiposity in T2DM-affected families is consistent with dominant expression of rare risk variants with major effects, which are expressed in over half of FH+ and which can account for most T2DM-associated obesity in our population. The calculated risk allele frequency in FH? suggests that rare genetic variants could also account for a substantial fraction of the prevalent obesity in this society.

Jenkins, Arthur B.; Batterham, Marijka; Samocha-Bonet, Dorit; Tonks, Katherine; Greenfield, Jerry R.; Campbell, Lesley V.

2013-01-01

397

Familial hypercholesterolaemia.  

PubMed

Familial hypercholesterolaemia (FH), defined as the heritable occurrence of severe hypercholesterolaemia with cholesterol deposits in tendons and premature heart disease, is caused by at least four genes in sterol and lipoprotein pathways and displays varying gene-dose effects. The genes are the low-density lipoprotein (LDL) receptor, apolipoprotein (apo) B, proprotein convertase subtilisin/kexin 9, and the autosomal recessive hypercholesterolaemia (ARH) adaptor protein. All of these disorders have in common defective clearance of LDL within a complex system of lipid and lipoprotein metabolism and regulation. Normal cellular cholesterol and lipoprotein metabolism is reviewed before describing the disorders, their metabolic derangements and their clinical effects. FH is classified as two simplified phenotypes of disease according to the severity of the metabolic derangement. The dominantly inherited heterozygous phenotype comprises defects in the LDL receptor, apoB100, and neural apoptosis regulatory cleavage protein. The homozygous phenotype is co-dominant in defects of the LDL receptor, and occurs also as the ARH of adapter protein mutations. Defective binding of apoB100 does not result in a significant gene dose effect, but enhances the severity of heterozygotes for LDL receptor mutations. The genetic diagnosis of FH has provided greater accuracy in definition and detection of disease and exposes information about migration of populations. All of these disorders pose a high risk of atherosclerosis, especially in the homozygous phenotype. Studies of influences on the phenotype and responses to treatment are also discussed in the context of the metabolic derangements. PMID:18516203

Marais, A David

2004-02-01

398

Impact Of Family Environment On Disordered Eating In Overweight Adolescents.  

National Technical Information Service (NTIS)

Research has shown that overweight and disordered eating are often comorbid especially in the context of poor family functioning and negative affect. The role of family structure remains largely unexplored, and no single study has examined all of these va...

D. A. Ross

2008-01-01

399

Family Reintegration Following Guard Deployment.  

National Technical Information Service (NTIS)

As large numbers of deployed Guard members have returned home, there is still concern that they may not have been fully prepared to face the challenges of family reintegration. Though return from deployment can be a happy occasion, homecoming can turn int...

D. C. Messecar

2005-01-01

400

Detection of a rare mutation in an Iranian family: codons 37/38/39 (7 bp deletion).  

PubMed

We recently found a rare beta(0)-thalassemia (beta(0)-thal) mutation, namely codons 37/38/39 (-GACCCAG), in a consanguineous family from southeast Iran. The first cousin couple was heterozygous for the mutation. They had a healthy 4-year-old daughter and were referred to us for prenatal diagnosis at 6 weeks gestation in the second pregnancy. The fetus, based on results of sequencing of the beta-globing gene, was homozygous for the same mutation. Results of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) on detection of this 7 bp deletion, and also restriction fragment length polymorphism (RFLP) analysis confirmed the homozygosity of the fetus. PMID:19958201

Zadeh-Vakili, Azita; Eshghi, Payman

2009-01-01

401

Bounding CKM Mixing with a Fourth Family  

SciTech Connect

CKM mixing between third family quarks and a possible fourth family is constrained by global fits to the precision electroweak data. The dominant constraint is from nondecoupling oblique corrections rather than the vertex correction to Z {yields} {bar b}b used in previous analyses. The possibility of large mixing suggested by some recent analyses of FCNC processes is excluded, but 3-4 mixing of the same order as the Cabbibo mixing of the first two families is allowed.

Chanowitz, Michael S.

2009-04-22

402

Family and family therapy in Russia.  

PubMed

This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized. PMID:22515460

Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

2012-04-01

403

Family Literacy and ESL.  

ERIC Educational Resources Information Center

|Discusses family literacy and English as a Second Language, focusing on types of family literacy programs, issues in family literacy, and future directions in family literacy. Highlights one program and lists the components of three approaches to family literacy: intervention prevention, multiple literacies, and social change. (Author/VWL)|

Red, David L.

2003-01-01

404

Family Reading Night  

ERIC Educational Resources Information Center

|This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

2007-01-01

405

Family Reading Night  

ERIC Educational Resources Information Center

This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

2007-01-01

406

Family Homicide in  

Microsoft Academic Search

The family is viewed by most people as providing a nurturing and loving environment. But for some, the family environment can be deadly. In Australia, almost two in five homicides occur between family members, with an average of 129 family homicides each year. The majority of family homicides occur between intimate partners (60 per cent), and three-quarters of intimate partner

Australia Jenny Mouzos; Catherine Rushforth; Adam Graycar

407

Small Family, Smart Family? Family Size and the IQ Scores of Young Men  

Microsoft Academic Search

How do families influence the ability of children? Cognitive skills have been shown to be a strong predictor of educational attainment and future labor market success; as a result, understanding the determinants of cognitive skills can lead to a better understanding of children?s long run outcomes. This paper uses a large dataset on the male population of Norway and focuses

Sandra E. Black; Paul J. Devereux; Kjell G. Salvanes

2007-01-01

408

Pseudohypoaldosteronism: family studies to identify asymptomatic carriers by stimulation of the renin-aldosterone system.  

PubMed

Defective aldosterone receptor binding is present in pseudohypoaldosteronism, and sporadic as well as familial cases have been reported. In familial pseudohypoaldosteronism, autosomal dominant as well as autosomal recessive inheritance has been described. The autosomal dominant form is characterized by a relative mild course of the disease and asymptomatic carriers of the defect in these families, whereas the autosomal recessive form is characterized by severe salt-losing symptoms; not uncommonly these families are consanguineous. To date no genetic mutation has been identified in the aldosterone receptor gene of affected patients. Studies to evaluate the biochemical defect and to characterize the inheritance pattern are of major interest for clinical as well as research purposes. Thus we studied the response of the renin-angiotensin-aldosterone system to sodium depletion using a single dose of furosemide. In 5 patients from five nonconsanguineous families and in all available family members the renin and aldosterone levels as well as serum sodium was measured before and after an oral dose of furosemide. The aldosterone receptor binding of peripheral mononuclear leukocytes was determined at the beginning of the study. In three families asymptomatic carriers of the defect could be identified in the baseline state by elevated levels of basal aldosterone and high renin concentration. The levels of renin and aldosterone did not differ between the symptomatic and asymptomatic individuals in these families. Interestingly the aldosterone receptor binding in the asymptomatic carriers of these families was normal. In the other two families, however, the basal hormonal data were normal in all relatives suggesting at first sporadic cases. During sodium depletion with furosemide, renin as well as aldosterone levels rose significantly in 1 parent and a sibling, respectively. In contrast to the first three families the aldosterone receptor binding in these family members was low. We propose to reclassify these family members as asymptomatic carriers and the patients as familial cases. Whether these cases are genetically identical to the 'classical autosomal dominant cases' remains to be seen. It seems that the pathogenesis of pseudohypoaldosteronism is even more heterogeneous than previously thought and factors other than aldosterone receptor binding are crucial and need further identification. PMID:8894667

Kuhnle, U; Hinkel, G K; Hubl, W; Reichelt, T

1996-01-01

409

Family Preservation (Family Focus Research Project).  

National Technical Information Service (NTIS)

The Family Focus Research project provided a comprehensive evaluation of home-based crisis intervention strategies for families with children at risk of placement into substitute care. It examined the relative costs and benefits of three types of brief, i...

J. R. Taplin C. Rowland

1983-01-01

410

Family Child Care Licensing Study, 1997.  

ERIC Educational Resources Information Center

|This report details the findings of an annual survey of state child care regulatory agencies. The survey gathered data on both small family child care homes and group or large family child care homes in each of the 50 states, the District of Columbia, Puerto Rico and the Virgin Islands. The report's introduction lists the survey categories and…

Children's Foundation, Washington, DC.

411

Family Child Care Licensing Study, 1998.  

ERIC Educational Resources Information Center

|This report details a survey of state child care regulatory agencies. Data on both small family child care homes (FCCH) and group or large family child care homes (LCCH or GCCH) are included and organized into 22 categories: (1) number of regulated homes; (2) definitions and regulatory requirements; (3) unannounced inspection procedure; (4)…

Children's Foundation, Washington, DC.

412

Growth of Family Businesses and Small Firms  

Microsoft Academic Search

Abstract This study examines ownership structure and its affect on the growth of family businesses as compared,to small firms. A sample of small firms (735) examined,if goal conflict exists between managers and owners in small firms using regression analysis. Analysis suggests relationships in large firms may not be same in small and family firms. The use of economic variables in

Edward M. Hufft

413

America's Diverse Family Farms 2007 Edition  

Microsoft Academic Search

American farms encompass a wide range of sizes, ownership structures, and business types, but most farms are still family farms. Family farms account for 98 percent of farms and 85 percent of production. Although most farms are small and own most of the farmland, production has shifted to very large farms. Farms with sales of $1 million or more make

Robert A. Hoppe; David E. Banker; Penelope J. Korb; Erik J. ODonoghue; James M. MacDonald

2007-01-01

414

Familial atypical multiple mole-melanoma syndrome  

Microsoft Academic Search

A family is described showing concordance for malignant melanoma and a cutaneous phenotype characterised by multiple large moles of variable size and colour (reddish-brown to bright red) with pigmentary leakage. Transmission of the cutaneous phenotype in the subject family, and in several others currently under investigation, shows an inheritance pattern consistent with a simple autosomal dominant factor. This cutaneous phenotype

H T Lynch; B C Frichot; J F Lynch

1978-01-01

415

[Extreme degree familial hypobetalipoproteinemia caused by hypothetic double heterozygosity in a subject with severe mental deficiency].  

PubMed

We described the case of an adult male patient, seriously mentally deficient, hospitalised in Psychiatric Hospital for a period of many years, suffering from a familial hypobetalipoproteinemia with extremely low levels of plasmatic betalipoproteins. The patient has been followed and tested several times over a period of six years. Numerous members of his family, which is part of a restricted ethnic nucleus in a locality (Iolo) of the Comune of Prato in the Provincia of Florence, were examined and tested too. Consanguinity between his parents is not demonstrable. The diagnosis of homozygous hypobetalipoproteinemia is discarded, but it does not seem that the heterozygous one is to be accepted as weel. On the ground of the existence of two syndromes which are quite unlike each other, but both explainable as form of familial heterozygous hypobetalipoproteinemia, one of them present in his father, the other one in his mother and in the maternal relatives as in the patient's brother respectively, a hypothesis of a double heterozygosis could be formulated. Extant is the support of the recent literature data, depending on them the possibility of making the hypothesis of a multiplicity of the genes regulating the apolipoprotein B synthesis. We do not exclude that the peculiarity of the event of a double heterozygosis can also be directly responsible of the patient's serious mental deficiency, being at the same time more supportable the hypothesis of a encephalopathy in his early childhood. PMID:6545600

Acocella, M; Cossio, M; Barucci, M; Ciardetti, A; Archi, G; Rossini, R; Bassini, E; Lusetti, W

416

Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246  

SciTech Connect

This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbruck formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM). 41 refs., 3 figs., 5 tabs.

Levy, E. N.; Aksentijevich, I.; Pras, E. [National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD (United States)] [and others

1996-03-01

417

How to Pay a Non-family Manager in a Family Firm? a Multitask Principal-agent Analysis  

Microsoft Academic Search

A large number of family firms employ non-family managers as executives. This paper ana- lyzes the optimal compensation contract of a non-family manager that is employed by a fam- ily firm using principal-agent analysis. We show that in a situation where the business- owning family is primarily interested in the long-term survival of the firm, whereas the non- family manager

JÖRN HENDRICH BLOCK; JOACHIM HENKEL

418

Family Activities for Fitness  

ERIC Educational Resources Information Center

|This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.|

Grosse, Susan J.

2009-01-01

419

Contacting My Donor Family  

MedlinePLUS

... My Donor Family Newsroom Minorities Contacting My Donor Family Writing anything can be a challenge. Staring at ... down to write a note to your donor family can feeling overwhelming. The good news is that ...

420

Annual Family Income  

Center for Drug Evaluation (CDER)

... Annual Family Income. Statistics. N. Valid. Missing. Total annual family income, 904, 0. Total annual family income. Frequency. Percent. ... More results from www.fda.gov/drugs/developmentapprovalprocess/developmentresources

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