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Sample records for large consanguineous family

  1. Inhabitual autosomal recessive form of dentin dysplasia type I in a large consanguineous Moroccan family.

    PubMed

    Cherkaoui Jaouad, I; El Alloussi, M; Laarabi, F Z; Bouhouche, A; Ameziane, R; Sefiani, A

    2013-08-01

    Dentin dysplasia is a rare autosomal dominant genetic disease characterized by defect of dentin development and the causal gene is DSPP (Dentin Sialophosphoprotein gene). We report in the present study a large Moroccan family in which dentin dysplasia is clearly transmitted as an autosomal recessive trait. Four males and females family members born from healthy consanguineous parents are carriers of the typical features of the dentin dysplasia type I. Polymorphic markers that span the DSPP gene, allowed us to show that this locus is not linked to dentin dysplasia in our family. We also excluded in our family the SMOC2 gene (Sparc Related Modular Calcium Binding Protein 2) which was recently identified as a causal gene in dentin dysplasia type I with microdontia and misshapen teeth. This family represents, a new description of autosomal recessive pattern of inheritance of dentin dysplasia type I. Moreover, this form of dentin dysplasia is not allelic to the autosomal dominant dentin dysplasia and the genetic cause is to be discovered.

  2. A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.

    PubMed

    Khan, Muzammil A; Rupp, Verena M; Orpinell, Meritxell; Hussain, Muhammad S; Altmüller, Janine; Steinmetz, Michel O; Enzinger, Christian; Thiele, Holger; Höhne, Wolfgang; Nürnberg, Gudrun; Baig, Shahid M; Ansar, Muhammad; Nürnberg, Peter; Vincent, John B; Speicher, Michael R; Gönczy, Pierre; Windpassinger, Christian

    2014-11-15

    Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephaly.

  3. Benign muscular dystrophy: risk calculation in families with consanguinity.

    PubMed Central

    Wolff, G; Müller, C R; Grimm, T

    1989-01-01

    This report concerns two families in which the index patients are sporadic cases of a benign form of muscular dystrophy. In both families the sisters of the patients have married a close relative. The respective risks for a child of these consanguineous marriages being affected with either X linked Becker muscular dystrophy or autosomal recessive limb girdle muscular dystrophy is calculated using pedigree information, results of serum creatine kinase determinations, and also, in one family, results of DNA typing using RFLPs from the short arm of the X chromosome. PMID:2732990

  4. Genetic analysis of consanguineous families presenting with congenital ocular defects.

    PubMed

    Ullah, Ehsan; Nadeem Saqib, Muhammad Arif; Sajid, Sundus; Shah, Neelam; Zubair, Muhammad; Khan, Muzammil Ahmad; Ahmed, Iftikhar; Ali, Ghazanfar; Dutta, Atanu Kumar; Danda, Sumita; Lao, Richard; Ling-Fung Tang, Paul; Kwok, Pui-Yan; Ansar, Muhammad; Slavotinek, Anne

    2016-05-01

    Anophthalmia and microphthalmia (A/M) are a group of rare developmental disorders that affect the size of the ocular globe. A/M may present as the sole clinical feature, but are also frequently found in a variety of syndromes. A/M is genetically heterogeneous and can be caused by chromosomal aberrations, copy number variations and single gene mutations. To date, A/M has been caused by mutations in at least 20 genes that show different modes of inheritance. In this study, we enrolled eight consanguineous families with A/M, including seven from Pakistan and one from India. Sanger and exome sequencing of DNA samples from these families identified three novel mutations including two mutations in the Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3) gene, [c.1310_1311delAT; p.(Tyr437Trpfs*44) and c.964G > A; p.(Val322Met)] and a single missense mutation in Forkhead Box E3 (FOXE3) gene, [c.289A > G p.(Ile97Val)]. Additionally two previously reported mutations were identified in FOXE3 and in Visual System Homeobox 2 (VSX2). This is the first comprehensive study on families with A/M from the Indian subcontinent which provides further evidence for the involvement of known genes with novel and recurrent mutations.

  5. Loss of function mutations in RP1 are responsible for retinitis pigmentosa in consanguineous familial cases

    PubMed Central

    Kabir, Firoz; Ullah, Inayat; Ali, Shahbaz; Gottsch, Alexander D.H.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2016-01-01

    Purpose This study was undertaken to identify causal mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous families. Methods Large consanguineous families were ascertained from the Punjab province of Pakistan. An ophthalmic examination consisting of a fundus evaluation and electroretinography (ERG) was completed, and small aliquots of blood were collected from all participating individuals. Genomic DNA was extracted from white blood cells, and a genome-wide linkage or a locus-specific exclusion analysis was completed with polymorphic short tandem repeats (STRs). Two-point logarithm of odds (LOD) scores were calculated, and all coding exons and exon–intron boundaries of RP1 were sequenced to identify the causal mutation. Results The ophthalmic examination showed that affected individuals in all families manifest cardinal symptoms of RP. Genome-wide scans localized the disease phenotype to chromosome 8q, a region harboring RP1, a gene previously implicated in the pathogenesis of RP. Sanger sequencing identified a homozygous single base deletion in exon 4: c.3697delT (p.S1233Pfs22*), a single base substitution in intron 3: c.787+1G>A (p.I263Nfs8*), a 2 bp duplication in exon 2: c.551_552dupTA (p.Q185Yfs4*) and an 11,117 bp deletion that removes all three coding exons of RP1. These variations segregated with the disease phenotype within the respective families and were not present in ethnically matched control samples. Conclusions These results strongly suggest that these mutations in RP1 are responsible for the retinal phenotype in affected individuals of all four consanguineous families. PMID:27307693

  6. Identification of a homozygous splice site mutation in the dynein axonemal light chain 4 gene on 22q13.1 in a large consanguineous family from Pakistan with congenital mirror movement disorder.

    PubMed

    Ahmed, Iltaf; Mittal, Kirti; Sheikh, Taimoor I; Vasli, Nasim; Rafiq, Muhammad Arshad; Mikhailov, Anna; Ohadi, Mehrnaz; Mahmood, Huda; Rouleau, Guy A; Bhatti, Attya; Ayub, Muhammad; Srour, Myriam; John, Peter; Vincent, John B

    2014-11-01

    Mirror movements (MRMV) are involuntary movements on one side of the body that mirror voluntary movements on the opposite side. Congenital mirror movement disorder is a rare, typically autosomal-dominant disorder, although it has been suspected that some sporadic cases may be due to recessive inheritance. Using a linkage analysis and a candidate gene approach, two genes have been implicated in congenital MRMV disorder to date: DCC on 18q21.2 (MRMV1), which encodes a netrin receptor, and RAD51 on 15q15.1 (MRMV2), which is involved in the maintenance of genomic integrity. Here, we describe a large consanguineous Pakistani family with 11 cases of congenital MRMV disorder reported across five generations, with autosomal recessive inheritance likely. Sanger sequencing of DCC and RAD51 did not identify a mutation. We then employed microarray genotyping and autozygosity mapping to identify a shared region of homozygosity-by-descent among the affected individuals. We identified a large autozygous region of ~3.3 Mb on chromosome 22q13.1 (Chr22:36605976-39904648). We used Sanger sequencing to exclude several candidate genes within this region, including DMC1 and NPTXR. Whole exome sequencing was employed, and identified a splice site mutation in the dynein axonemal light chain 4 gene, DNAL4. This splice site change leads to skipping of exon 3, and omission of 28 amino acids from DNAL4 protein. Linkage analysis using Simwalk2 gives a maximum Lod score of 6.197 at this locus. Whether or how DNAL4 function may relate to the function of DCC or RAD51 is not known. Also, there is no suggestion of primary ciliary dyskinesis, situs inversus, or defective sperm in affected family members, which might be anticipated given a putative role for DNAL4 in axonemal-based dynein complexes. We suggest that DNAL4 plays a role in the cytoplasmic dynein complex for netrin-1-directed retrograde transport, and in commissural neurons of the corpus callosum in particular. This, in turn, could lead

  7. Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases

    PubMed Central

    Ullah, Inayat; Kabir, Firoz; Iqbal, Muhammad; Gottsch, Clare Brooks S.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2016-01-01

    Purpose To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous familial cases. Methods Seven large familial cases with multiple individuals diagnosed with retinitis pigmentosa were included in the study. Affected individuals in these families underwent ophthalmic examinations to document the symptoms and confirm the initial diagnosis. Blood samples were collected from all participating members, and genomic DNA was extracted. An exclusion analysis with microsatellite markers spanning the TULP1 locus on chromosome 6p was performed, and two-point logarithm of odds (LOD) scores were calculated. All coding exons along with the exon–intron boundaries of TULP1 were sequenced bidirectionally. We constructed a single nucleotide polymorphism (SNP) haplotype for the four familial cases harboring the K489R allele and estimated the likelihood of a founder effect. Results The ophthalmic examinations of the affected individuals in these familial cases were suggestive of RP. Exclusion analyses confirmed linkage to chromosome 6p harboring TULP1 with positive two-point LOD scores. Subsequent Sanger sequencing identified the single base pair substitution in exon14, c.1466A>G (p.K489R), in four families. Additionally, we identified a two-base deletion in exon 4, c.286_287delGA (p.E96Gfs77*); a homozygous splice site variant in intron 14, c.1495+4A>C; and a novel missense variation in exon 15, c.1561C>T (p.P521S). All mutations segregated with the disease phenotype in the respective families and were absent in ethnically matched control chromosomes. Haplotype analysis suggested (p<10−6) that affected individuals inherited the causal mutation from a common ancestor. Conclusions Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. PMID:27440997

  8. Genetic counseling of consanguineous families. Use of Smith's method to calculate recurrence risks in multifactorial inheritance in consanguineous matings.

    PubMed Central

    Bonaiti, C

    1978-01-01

    A modification of Smith's method is described for deriving recurrence risks for multifactorial conditions when parents are related. Using cleft palate as an example, the possible increased risks caused by consanguinity are discussed. PMID:641942

  9. Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness.

    PubMed

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

    2008-01-01

    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 linkage and mutational analysis revealed, instead of an expected homozygous mutation in a single gene, two different mutant alleles and a possible third undetected mutant allele in the MYO15A gene (DFNB3 locus), as well as evidence for other causes for deafness in the same pedigree. Among the 26 affected subjects, 15 were homozygous for the novel c.10573delA mutation in the MYO15A gene, 5 were compound heterozygous for the mutation c.10573delA and the novel deletion c.9957_9960delTGAC and one inherited only a single c.10573delA mutant allele, while the other one could not be identified. Given the extensive consanguinity of the pedigree, there might be at least one more deafness locus segregating to explain the condition in some of the subjects whose deafness is not clearly associated with MYO15A mutations, although overlooked environmental causes could not be ruled out. Our findings illustrate a high level of etiological heterogeneity for deafness in the family and highlight some of the pitfalls of genetic analysis of large genes in extended pedigrees, when homozygosity for a single mutant allele is expected.

  10. A Common Ancestral Mutation in CRYBB3 Identified in Multiple Consanguineous Families with Congenital Cataracts

    PubMed Central

    Irum, Bushra; Khan, Arif O.; Wang, Qiwei; Li, David; Khan, Asma A.; Husnain, Tayyab; Akram, Javed; Riazuddin, Sheikh

    2016-01-01

    Purpose This study was performed to investigate the genetic determinants of autosomal recessive congenital cataracts in large consanguineous families. Methods Affected individuals underwent a detailed ophthalmological examination and slit-lamp photographs of the cataractous lenses were obtained. An aliquot of blood was collected from all participating family members and genomic DNA was extracted from white blood cells. Initially, a genome-wide scan was performed with genomic DNAs of family PKCC025 followed by exclusion analysis of our familial cohort of congenital cataracts. Protein-coding exons of CRYBB1, CRYBB2, CRYBB3, and CRYBA4 were sequenced bidirectionally. A haplotype was constructed with SNPs flanking the causal mutation for affected individuals in all four families, while the probability that the four familial cases have a common founder was estimated using EM and CHM-based algorithms. The expression of Crybb3 in the developing murine lens was investigated using TaqMan assays. Results The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis localized the causal phenotype in family PKCC025 to chromosome 22q with statistically significant two-point logarithm of odds (LOD) scores. Subsequently, we localized three additional families, PKCC063, PKCC131, and PKCC168 to chromosome 22q. Bidirectional Sanger sequencing identified a missense variation: c.493G>C (p.Gly165Arg) in CRYBB3 that segregated with the disease phenotype in all four familial cases. This variation was not found in ethnically matched control chromosomes, the NHLBI exome variant server, or the 1000 Genomes or dbSNP databases. Interestingly, all four families harbor a unique disease haplotype that strongly suggests a common founder of the causal mutation (p<1.64E-10). We observed expression of Crybb3 in the mouse lens as early as embryonic day 15 (E15), and expression remained relatively steady throughout

  11. Wolcott-Rallison Syndrome Is the Most Common Genetic Cause of Permanent Neonatal Diabetes in Consanguineous Families

    PubMed Central

    Rubio-Cabezas, Oscar; Patch, Ann-Marie; Minton, Jayne A. L.; Flanagan, Sarah E.; Edghill, Emma L.; Hussain, Khalid; Balafrej, Amina; Deeb, Asma; Buchanan, Charles R.; Jefferson, Ian G.; Mutair, Angham; Hattersley, Andrew T.; Ellard, Sian

    2009-01-01

    Context and Objective: Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction. Although early diagnosis is important for clinical management, genetic testing is generally performed after the full clinical picture develops. We aimed to identify patients with WRS before any other abnormalities apart from diabetes are present and study the overall frequency of WRS among patients with permanent neonatal diabetes. Research Design and Methods: The coding regions of EIF2AK3 were sequenced in 34 probands with infancy-onset diabetes with a clinical phenotype suggestive of WRS (n = 28) or homozygosity at the WRS locus (n = 6). Results: Twenty-five probands (73.5%) were homozygous or compound heterozygous for mutations in EIF2AK3. Twenty of the 26 mutations identified were novel. Whereas a diagnosis of WRS was suspected before genetic testing in 22 probands, three patients with apparently isolated diabetes were diagnosed after identifying a large homozygous region encompassing EIF2AK3. In contrast to nonconsanguineous pedigrees, mutations in EIF2AK3 are the most common known genetic cause of diabetes among patients born to consanguineous parents (24 vs. < 2%). Age at diabetes onset and birth weight might be used to prioritize genetic testing in the latter group. Conclusions: WRS is the most common cause of permanent neonatal diabetes mellitus in consanguineous pedigrees. In addition to testing patients with a definite clinical diagnosis, EIF2AK3 should be tested in patients with isolated neonatal diabetes diagnosed after 3 wk of age from known consanguineous families, isolated populations, or countries in which inbreeding is frequent. PMID:19837917

  12. A new autosomal recessive non-progressive congenital cerebellar ataxia associated with mental retardation, optic atrophy, and skin abnormalities (CAMOS) maps to chromosome 15q24-q26 in a large consanguineous Lebanese Druze Family.

    PubMed

    Delague, Valérie; Bareil, Corinne; Bouvagnet, Patrice; Salem, Nabiha; Chouery, Eliane; Loiselet, Jacques; Mégarbané, André; Claustres, Mireille

    2002-03-01

    Congenital cerebellar ataxias are a heterogeneous group of non-progressive disorders characterized by hypotonia and developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We report the mapping of a disease gene in a large inbred Lebanese Druze family, with five cases of a new form of non-progressive autosomal recessive congenital ataxia associated with optic atrophy, severe mental retardation, and structural skin abnormalities, to a 3.6-cM interval on chromosome 15q24-15q26.

  13. Gene mapping in an anophthalmic pedigree of a consanguineous Pakistani family opened new horizons for research

    PubMed Central

    Ajmal, M; Zafar, S; Hameed, A

    2016-01-01

    ABSTRACT Clinical anophthalmia is a rare inherited disease of the eye and phenotype refers to the absence of ocular tissue in the orbit of eye. Patients may have unilateral or bilateral anophthalmia, and generally have short palpebral fissures and small orbits. Anophthalmia may be isolated or associated with a broader syndrome and may have genetic or environmental causes. However, genetic cause has been defined in only a small proportion of cases, therefore, a consanguineous Pakistani family of the Pashtoon ethnic group, with isolated clinical anophthalmia was investigated using linkage mapping. A family pedigree was created to trace the possible mode of inheritance of the disease. Blood samples were collected from affected as well as normal members of this family, and screened for disease-associated mutations. This family was analyzed for linkage to all the known loci of clinical anophthalmia, using microsatellite short tandem repeat (STR) markers. Direct sequencing was performed to find out disease-associated mutations in the candidate gene. This family with isolated clinical anophthalmia, was mapped to the SOX2 gene that is located at chromosome 3q26.3-q27. However, on exonic and regulatory regions mutation screening of the SOX2 gene, the disease-associated mutation was not identified. It showed that another gene responsible for development of the eye might be present at chromosome 3q26.3-q27 and needs to be identified and screened for the disease-associated mutation in this family. PMID:27785411

  14. Genetic dissection of two Pakistani families with consanguineous localized autosomal recessive hypotrichosis (LAH)

    PubMed Central

    Abbas, Seyyedha; Naveed, Abdul Khaliq; Khan, Shakir; Yousaf, Muhammad Jawad; Azeem, Zahid; Razak, Suhail; Qaiser, Fatima

    2014-01-01

    Objective(s): Genetic analysis of two consanguineous Pakistani families with localized autosomal recessive hypotrichosis was performed with the goal to establish genotype-phenotype correlation. Materials and Methods: Genomic DNA extraction had been done from peripheral blood samples. Extracted DNA was then subjected to PCR (polymerase chain reaction) for amplification. Linkage analysis was performed using 8% polyacrylamide gel. Candidate gene was sequenced after gene linkage supported at highly polymorphic microsatellite markers of the diseased region. Results: Both families were initially tested for linkage to known genes, which were involved in human hereditary hypotrichosis, by genotyping Highly polymorphic microsatellite markers. Family B showed partial linkage at P2RY5 gene on chromosome 13q14.11-q21.32; hence, all exonic regions and their introns boundaries were subjected to DNA sequencing for any pathogenic mutation. Conclusion: Both families were tested for linkage by genotyping polymorphic microsatellite markers linked to known alopecia loci. Family A excluded all known diseased regions that is suggestive of some novel chromosomal disorder. However, sequencing of P2RY5 gene in family B showed no pathogenic mutation. PMID:25429336

  15. WDR62 missense mutation in a consanguineous family with primary microcephaly.

    PubMed

    Bacino, Carlos A; Arriola, Luis A; Wiszniewska, Joanna; Bonnen, Penelope E

    2012-03-01

    We report on a consanguineous couple with two affected sons who presented with primary microcephaly and moderate to severe intellectual disabilities. A SNP array uncovered two overlapping regions of copy-neutral absence of heterozygosity (AOH) in both sibs. This led to sequencing of WDR62, a gene that codes for a spindle pole protein recently identified as a cause of primary microcephaly. A homozygous missense mutation in WDR62, p.E400K, was found in both boys and segregated with the condition in this family. WDR62 is one of seven genes responsible for autosomal recessive primary microcephaly (MCPH), and appears to be one of the most frequently involved in MCPH following ASPM. Studies of ASPM and WDR62 should perhaps be pursued in all cases of primary microcephaly with or without gross brain malformations.

  16. Novel CYP1B1 mutations in consanguineous Pakistani families with primary congenital glaucoma

    PubMed Central

    Firasat, Sabika; Khan, Shaheen N.

    2008-01-01

    Purpose To identify the disease-causing mutations in three consanguineous Pakistani families with multiple members affected by primary congenital glaucoma. Methods Blood samples were collected, and DNA was extracted. Linkage analysis for reported primary congenital glaucoma loci was performed using closely spaced polymorphic microsatellite markers on genomic DNA from affected and unaffected family members. All coding exons, the exon-intron boundaries, and the 5′ untranslated region of CYP1B1 were sequenced. Results The alleles of chromosome 2p markers segregate with the disease phenotype in all three families with positive LOD scores. The sequencing results identified three novel mutations (L177R, L487P, and D374E) and one previously reported mutation (E229K) in CYP1B1 that segregate with the disease phenotype in their respective families. None of these sequence variations were present in 96 ethnically matched control samples. Conclusions These results strongly suggest that missense mutations in CYP1B1 are most likely to be responsible for primary congenital glaucoma in these families. PMID:18989382

  17. Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family.

    PubMed

    Chograni, M; Alkuraya, F S; Ourteni, I; Maazoul, F; Lariani, I; Chaabouni, H B

    2015-09-01

    The aim of this study is to investigate the genetic basis of autosomal recessive congenital cataract and intellectual disability phenotype in a consanguineous Tunisian family. The whole genome scan of the studied family was performed with single nucleotide polymorphisms (SNPs). The resulted runs of homozygosity (ROH) were analyzed through the integrated Systems Tool for Eye gene discovery (iSyTE) in order to prioritize candidate genes associated with congenital cataract. Selected genes were amplified and sequenced. Bioinformatic analysis was conducted to predict the function of the mutant gene. We identified a new specific lens gene named syntaxin 3 linked to the studied phenotype. The direct sequencing of this gene revealed a novel missense mutation c.122A>G which results in p.E41G. Bioinformatic analysis suggested a deleterious effect of this mutation on protein structure and function. Here, we report for the first time a missense mutation of a novel lens specific gene STX3 in a phenotype associating autosomal recessive congenital cataract and intellectual disability.

  18. Consanguineous marriage in Iran.

    PubMed

    Saadat, M; Ansari-Lari, M; Farhud, D D

    2004-01-01

    Consanguineous marriage is a major feature of family systems in south-west Asia. The aim of the present study was to determine the current prevalence and patterns of consanguinity in Iran as a means of assessing the associated requirement for genetic counselling services. Consanguinity was studied in 12 ethnic/religious populations, the Persians (Shi'a and Sunni), Kurds (Shi'a and Sunni), Lurs, Azaris, Baluchis, Zabolis, Turkamans, Bakhtiaris, Ghashghais and Arabs. A multi-stage sampling design was used with a representative total sample of 306 343 couples. The overall rate of consanguineous marriage was 38.6% with a mean inbreeding coefficient (alpha) of 0.0185. First cousin marriages (27.9%) were the most common form of consanguineous union, with parallel patrilateral marriage especially favoured. Statistically significant differences were observed in the prevalence and patterns of consanguinity between ethnic/religious populations and geographical regions. There also were significant differences for proportions of consanguineous marriages between Shi'a and Sunni populations within the same ethnic group. The highest rates of consanguineous union were in the least affluent sections of the population. PMID:15204368

  19. Consanguineous marriage in Iran.

    PubMed

    Saadat, M; Ansari-Lari, M; Farhud, D D

    2004-01-01

    Consanguineous marriage is a major feature of family systems in south-west Asia. The aim of the present study was to determine the current prevalence and patterns of consanguinity in Iran as a means of assessing the associated requirement for genetic counselling services. Consanguinity was studied in 12 ethnic/religious populations, the Persians (Shi'a and Sunni), Kurds (Shi'a and Sunni), Lurs, Azaris, Baluchis, Zabolis, Turkamans, Bakhtiaris, Ghashghais and Arabs. A multi-stage sampling design was used with a representative total sample of 306 343 couples. The overall rate of consanguineous marriage was 38.6% with a mean inbreeding coefficient (alpha) of 0.0185. First cousin marriages (27.9%) were the most common form of consanguineous union, with parallel patrilateral marriage especially favoured. Statistically significant differences were observed in the prevalence and patterns of consanguinity between ethnic/religious populations and geographical regions. There also were significant differences for proportions of consanguineous marriages between Shi'a and Sunni populations within the same ethnic group. The highest rates of consanguineous union were in the least affluent sections of the population.

  20. A community genetics perspective on consanguineous marriage.

    PubMed

    Bittles, A H

    2008-01-01

    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 also been paid to the social benefits associated with intra-familial marriage, resulting in a biased overall cost-benefit assessment. Worldwide, some 1,000 million people live in countries where 20 to more than 50% of marriages are consanguineous, and large migrant communities from these regions are now resident in Western Europe, North America and Oceania. The need for comprehensive and more balanced investigations into all aspects of consanguineous marriage is pressing and merits a substantial international collaborative research effort.

  1. Initial expression of the Papillon-Lefèvre syndrome in consanguine family

    PubMed Central

    Singh, Anand Pratap; Chaitra, T R; Singh, Surendra Pratap; Kulkarni, Adwait Uday

    2012-01-01

    A rare case of Papillon-Lefevre syndrome is discussed with clinicoradiological presentation. The purpose of the case report is to make the medical community aware of this rare syndrome and its association with consanguinity. Papillon-Lefevre syndrome is an extremely rare genodermatosis of autosomal-recessive inheritance which usually manifests itself between the ages of 6 months to 4 years characterised by diffuse palmoplanter hyperkeratosis (keratoderma), and rapidly progressive and devastating periodontitis, affecting the primary as well as permanent dentition. Papillon-Lefevre syndrome results from a combination of host and bacterial factors, including recessive gene, consanguinity, specific periodontal pathogens and lack of thorough oral hygiene. The present case report describes Papillon-Lefevre syndrome and its association with consanguinity in a 3-year-old girl. PMID:22922917

  2. Practice of Consanguinity and Unusual Cases of Inherited Familial Chromosome Abnormalities: A Case Report

    PubMed Central

    Sanyal, Debarshi; Bhairi, Vidya; S Kadandale, Jayarama

    2016-01-01

    We present 2 cases of likely rare event. In case 1, 3rd degree consanguineous marriage revealed inv(6) with same break points in parents who were found to be phenotypically normal. The same inv(6) being inherited in progeny but presented with low AMH (anti Mullerian hormone) and high level of FSH (follicular stimulating hormone) leading to polycystic ovarian syndrome/premature ovarian failure. In case 2, a couple was presented with 2nd degree consanguineous marriage and referred for 2 recurrent/ missed abortions. The amounts of shared genes are suggestive of more lethal genetic outcomes and inferred endogamy is a major driver to reproductive fiascoes, the ancestries of which are deeply tied at the meiotic level. PMID:27386439

  3. Practice of Consanguinity and Unusual Cases of Inherited Familial Chromosome Abnormalities: A Case Report.

    PubMed

    Sanyal, Debarshi; Bhairi, Vidya; S Kadandale, Jayarama

    2016-01-01

    We present 2 cases of likely rare event. In case 1, 3(rd) degree consanguineous marriage revealed inv(6) with same break points in parents who were found to be phenotypically normal. The same inv(6) being inherited in progeny but presented with low AMH (anti Mullerian hormone) and high level of FSH (follicular stimulating hormone) leading to polycystic ovarian syndrome/premature ovarian failure. In case 2, a couple was presented with 2(nd) degree consanguineous marriage and referred for 2 recurrent/ missed abortions. The amounts of shared genes are suggestive of more lethal genetic outcomes and inferred endogamy is a major driver to reproductive fiascoes, the ancestries of which are deeply tied at the meiotic level. PMID:27386439

  4. Mutations in ALDH1A3 represent a frequent cause of microphthalmia/anophthalmia in consanguineous families.

    PubMed

    Abouzeid, Hana; Favez, Tatiana; Schmid, Angélique; Agosti, Céline; Youssef, Mohammed; Marzouk, Iman; El Shakankiry, Nihal; Bayoumi, Nader; Munier, Francis L; Schorderet, Daniel F

    2014-08-01

    Anophthalmia or microphthalmia (A/M), characterized by absent or small eye, can be unilateral or bilateral and represent developmental anomalies due to the mutations in several genes. Recently, mutations in aldehyde dehydrogenase family 1, member A3 (ALDH1A3) also known as retinaldehyde dehydrogenase 3, have been reported to cause A/M. Here, we screened a cohort of 75 patients with A/M and showed that mutations in ALDH1A3 occurred in six families. Based on this series, we estimate that mutations in ALDH1A3 represent a major cause of A/M in consanguineous families, and may be responsible for approximately 10% of the cases. Screening of this gene should be performed in a first line of investigation, together with SOX2.

  5. Specific aspects of consanguinity: some examples from the Tunisian population.

    PubMed

    Romdhane, Lilia; Ben Halim, Nizar; Rejeb, Insaf; Kefi, Rym; Bouyacoub, Yosra; Ben Rekaya, Mariem; Messai, Habib; Messaoud, Olfa; Riahi, Zied; Bonnet, Crystel; Ben Rhouma, Faten; Nagara, Majdi; Petit, Christine; McElreavey, Ken; Romeo, Giovanni; Abdelhak, Sonia

    2014-01-01

    Located at the cross-road between Europe and Africa, Tunisia is a North African country of 11 million inhabitants. Throughout its history, it has been invaded by different ethnic groups. These historical events, and consanguinity, have impacted on the spectrum and frequency of genetic diseases in Tunisia. Investigations of Tunisian families have significantly contributed to elucidation of the genetic bases of rare disorders, providing an invaluable resource of cases due to particular familial structures (large family size, consanguinity and share of common ancestors). In the present study, we report on and review different aspects of consanguinity in the Tunisian population as a case study, representing several features common to neighboring or historically related countries in North Africa and the Middle East. Despite the educational, demographic and behavioral changes that have taken place during the last four decades, familial and geographical endogamy still exist at high frequencies, especially in rural areas. The health implications of consanguinity in Tunisian families include an increased risk of the expression of autosomal recessive diseases and particular phenotypic expressions. With new sequencing technologies, the investigation of consanguineous populations provides a unique opportunity to better evaluate the impact of consanguinity on the genome dynamic and on health, in addition to a better understanding of the genetic bases of diseases. PMID:25060280

  6. Consanguineous marriage and its relevance to obstetric practice.

    PubMed

    de Costa, Caroline M

    2002-08-01

    At the beginning of the twenty-first century, consanguineous marriage is practiced widely in many parts of the world. More than 2 billion people, of various religious and ethnic backgrounds, live in countries where a large proportion of marriages are contracted between blood relatives. The practice is seen as promoting family stability and having significant social and economic advantages. Consanguineous marriage is important genetically-the children of consanguineous unions are more often homozygous for particular alleles than are the offspring of unrelated parents, and therefore, autosomal recessive disorders, which may be lethal or debilitating, are more common in such children. Health-care providers working with communities where consanguineous marriage is common, in particular obstetricians, family physicians, and pediatricians, need to be aware of the possible impact of such marriages on pregnancy outcomes, so the best possible genetic and antenatal care can be provided, sympathetically and nonjudgmentally, and the best possible results obtained.

  7. Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy

    PubMed Central

    Nikopoulos, Konstantinos; Avila-Fernandez, Almudena; Corton, Marta; Lopez-Molina, Maria Isabel; Perez-Carro, Raquel; Bontadelli, Lara; Di Gioia, Silvio Alessandro; Zurita, Olga; Garcia-Sandoval, Blanca; Rivolta, Carlo; Ayuso, Carmen

    2015-01-01

    Inherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients’ molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision, reduced or absent ERG responses, macular atrophy and pigmentary deposits in the peripheral retina. Genetic investigation included autozygosity mapping coupled with exome sequencing in the first family, whereas autozygome-guided candidate gene screening was performed by means of Sanger DNA sequencing in the second family. Our approach revealed nucleotide changes in CDHR1; a homozygous missense variant (c.1720C > G, p.P574A) and a homozygous single base transition (c.1485 + 2T > C) affecting the canonical 5’ splice site of intron 13, respectively. Both changes co-segregated with the disease and were absent among cohorts of unrelated control individuals. To date, only five mutations in CDHR1 have been identified, all resulting in premature stop codons leading to mRNA nonsense mediated decay. Our work reports two previously unidentified homozygous mutations in CDHR1 further expanding the mutational spectrum of this gene. PMID:26350383

  8. Effect of consanguinity among North India Muslims.

    PubMed

    Basu, S K

    1975-01-01

    Endogamous Muslim groups in Delhi and Lucknow, India, were studied to discover the effects of consanguineous marriage on fertility, mortality, and net-fertility rates. Sayyad Shias have a much higher frequency of parental consanguinity. Consanguineous marriages occurred among the following groups in descending order of frequency: Sheikh, Pathan, and Moghul Sumnis. Different forms of inbreeding occurred among the various groups. Most Muslims oppose family planning on religous grounds. In both Sayyad Shias and Sheikh Sumni consanguineous marriages there was a higher fertility rate than among non-consanguineous marriages. The net-fertility rate was not higher, because mortality before 21 was highest among first cousins. PMID:12307582

  9. Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer's disease identifies a homozygous CTSF mutation.

    PubMed

    Bras, Jose; Djaldetti, Ruth; Alves, Ana Margarida; Mead, Simon; Darwent, Lee; Lleo, Alberto; Molinuevo, Jose Luis; Blesa, Rafael; Singleton, Andrew; Hardy, John; Clarimon, Jordi; Guerreiro, Rita

    2016-10-01

    We have previously reported the whole genome genotyping analysis of 2 consanguineous siblings clinically diagnosed with early onset Alzheimer's disease (AD). In this analysis, we identified several large regions of homozygosity shared between both affected siblings, which we suggested could be candidate loci for a recessive genetic lesion underlying the early onset AD in these cases. We have now performed exome sequencing in one of these siblings and identified the potential cause of disease: the CTSF c.1243G>A:p.Gly415Arg mutation in homozygosity. Biallelic mutations in this gene have been shown to cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis with some cases resembling the impairment seen in AD. PMID:27524508

  10. Consanguinity and dysmorphology in Arabs.

    PubMed

    Al-Gazali, Lihadh; Hamamy, Hanan

    2014-01-01

    Incidence rates of congenital disorders among the 350 million inhabitants of Arab countries could be influenced via the people's demographic and cultural characteristics. Arabs usually marry at a young age and have large families. They share certain core cultural values and beliefs, with the family accepted as the central structure of society. Consanguineous marriage is favored and respected in most if not all Arab communities, and intrafamilial unions currently account for 20-50% of all marriages. First-cousin unions are especially popular and constitute almost one quarter of all marriages in many Arab countries. Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a considerable proportion of all birth defects among Arabs. Arab geneticists, with their persistent commitment to advancing research, have contributed to the description of a number of rare and new AR syndromes with the identification of novel genes. The collaboration with research teams in high-income countries resulted in a plethora of data on pathogenic variants and their function in causing dysmorphic syndromes. There could still be a considerable number of rare dysmorphic syndromes that prevail among Arabs which are not hitherto described and whose underlying molecular pathologies are not yet defined. Arab countries should thus strive to deploy DNA diagnostics and to build research capability around local priorities. Furthermore, a characterization of the prevailing genetic disorders in each geographic location, together with their mutations, is needed to plan for appropriate screening and testing protocols. An overview of consanguinity in Arab countries and examples of dysmorphology syndromes associated with consanguinity with their available molecular bases will be discussed.

  11. A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia.

    PubMed

    Roos, L; Fang, M; Dali, C; Jensen, H; Christoffersen, N; Wu, B; Zhang, J; Xu, R; Harris, P; Xu, X; Grønskov, K; Tümer, Z

    2014-09-01

    Anomalies of eye development can lead to the rare eye malformations microphthalmia and anophthalmia (small or absent ocular globes), which are genetically very heterogeneous. Several genes have been associated with microphthalmia and anophthalmia, and exome sequencing has contributed to the identification of new genes. Very recently, homozygous variations within ALDH1A3 have been associated with autosomal recessive microphthalmia with or without cysts or coloboma, and with variable subphenotypes of developmental delay/autism spectrum disorder in eight families. In a consanguineous family where three of the five siblings were affected with microphthalmia/coloboma, we identified a novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the three affected siblings, one had intellectual disability and one had intellectual disability and autism, while the last one presented with normal development. This study contributes further to the description of the clinical spectrum associated with ALDH1A3 mutations, and illustrates the interfamilial clinical variation observed in individuals with ALDH1A3 mutations.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22428046

  13. A novel frameshift mutation in FGA (c.1846 del A) leading to congenital afibrinogenemia in a consanguineous Syrian family.

    PubMed

    Levrat, Emmanuel; Aboukhamis, Imad; de Moerloose, Philippe; Farho, Jaafar; Chamaa, Sahar; Reber, Guido; Fort, Alexandre; Neerman-Arbez, Marguerite

    2011-03-01

    Congenital afibrinogenemia is a rare autosomal recessive coagulation disorder characterized essentially by bleeding symptoms, but miscarriages and, paradoxically, thromboembolic events can also occur. Most reported mutations leading to congenital afibrinogenemia are located in FGA encoding the fibrinogen A α-chain. In this study, we analysed 12 individuals from a consanguineous Syrian family with reduced or absent fibrinogen levels: those with fibrinogen levels around 1 g/l (n = 7) were found to be heterozygous for a novel frameshift mutation in FGA exon 5 (c.1846 del A) and those with undetectable fibrinogen levels (n = 5) were homozygous for the same mutation. This novel frameshift mutation is the most C-terminal causative FGA mutation identified to date in afibrinogenemic patients. The resulting aberrant Aα-chain (p.Thr616HisfsX32) is most likely synthesized, but is less efficiently assembled and/or secreted into the circulation given the phenotype of asymptomatic hypofibrinogenemia in heterozygous individuals and bleeding diathesis in homozygous individuals.

  14. Exome sequencing identified a novel de novo OPA1 mutation in a consanguineous family presenting with optic atrophy.

    PubMed

    Cohen, Lior; Tzur, Shay; Goldenberg-Cohen, Nitza; Bormans, Concetta; Behar, Doron M; Reinstein, Eyal

    2016-01-01

    Inherited optic neuropathies are a heterogeneous group of disorders characterized by mild to severe visual loss, colour vision deficit, central or paracentral visual field defects and optic disc pallor. Optic atrophies can be classified into isolated or non-syndromic and syndromic forms. While multiple modes of inheritance have been reported, autosomal dominant optic atrophy and mitochondrial inherited Leber's hereditary optic neuropathy are the most common forms. Optic atrophy type 1, caused by mutations in the OPA1 gene is believed to be the most common hereditary optic neuropathy, and most patients inherit a mutation from an affected parent. In this study we used whole-exome sequencing to investigate the genetic aetiology in a patient affected with isolated optic atrophy. Since the proband was the only affected individual in his extended family, and was a product of consanguineous marriage, homozygosity mapping followed by whole-exome sequencing were pursued. Exome results identified a novel de novo OPA1 mutation in the proband. We conclude, that though de novo OPA1 mutations are uncommon, testing of common optic atrophy-associated genes such as mitochondrial mutations and OPA1 gene sequencing should be performed first in single individuals presenting with optic neuropathy, even when dominant inheritance is not apparent.

  15. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.

    PubMed

    Alazami, Anas M; Patel, Nisha; Shamseldin, Hanan E; Anazi, Shamsa; Al-Dosari, Mohammed S; Alzahrani, Fatema; Hijazi, Hadia; Alshammari, Muneera; Aldahmesh, Mohammed A; Salih, Mustafa A; Faqeih, Eissa; Alhashem, Amal; Bashiri, Fahad A; Al-Owain, Mohammed; Kentab, Amal Y; Sogaty, Sameera; Al Tala, Saeed; Temsah, Mohamad-Hani; Tulbah, Maha; Aljelaify, Rasha F; Alshahwan, Saad A; Seidahmed, Mohammed Zain; Alhadid, Adnan A; Aldhalaan, Hesham; AlQallaf, Fatema; Kurdi, Wesam; Alfadhel, Majid; Babay, Zainab; Alsogheer, Mohammad; Kaya, Namik; Al-Hassnan, Zuhair N; Abdel-Salam, Ghada M H; Al-Sannaa, Nouriya; Al Mutairi, Fuad; El Khashab, Heba Y; Bohlega, Saeed; Jia, Xiaofei; Nguyen, Henry C; Hammami, Rakad; Adly, Nouran; Mohamed, Jawahir Y; Abdulwahab, Firdous; Ibrahim, Niema; Naim, Ewa A; Al-Younes, Banan; Meyer, Brian F; Hashem, Mais; Shaheen, Ranad; Xiong, Yong; Abouelhoda, Mohamed; Aldeeri, Abdulrahman A; Monies, Dorota M; Alkuraya, Fowzan S

    2015-01-13

    Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function.

  16. Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing

    PubMed Central

    Lal, Dennis; Neubauer, Bernd A.; Toliat, Mohammad R.; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Kamrath, Clemens; Schänzer, Anne; Sander, Thomas; Hahn, Andreas; Nothnagel, Michael

    2016-01-01

    Massively parallel sequencing of whole genomes and exomes has facilitated a direct assessment of causative genetic variation, now enabling the identification of genetic factors involved in rare diseases (RD) with Mendelian inheritance patterns on an almost routine basis. Here, we describe the illustrative case of a single consanguineous family where this strategy suffered from the difficulty to distinguish between two etiologically distinct disorders, namely the co-occurrence of hereditary hypophosphatemic rickets (HRR) and congenital myopathies (CM), by their phenotypic manifestation alone. We used parametric linkage analysis, homozygosity mapping and whole exome-sequencing to identify mutations underlying HRR and CM. We also present an approximate approach for assessing the probability of co-occurrence of two unlinked recessive RD in a single family as a function of the degree of consanguinity and the frequency of the disease-causing alleles. Linkage analysis and homozygosity mapping yielded elusive results when assuming a single RD, but whole-exome sequencing helped to identify two mutations in two genes, namely SLC34A3 and SEPN1, that segregated independently in this family and that have previously been linked to two etiologically different diseases. We assess the increase in chance co-occurrence of rare diseases due to consanguinity, i.e. under circumstances that generally favor linkage mapping of recessive disease, and show that this probability can increase by several orders of magnitudes. We conclude that such potential co-occurrence represents an underestimated risk when analyzing rare or undefined diseases in consanguineous families and should be given more consideration in the clinical and genetic evaluation. PMID:26789268

  17. In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype

    PubMed Central

    Saleha, Shamim; Ajmal, Muhammad; Jamil, Muhammad; Nasir, Muhammad; Hameed, Abdul

    2016-01-01

    AIM To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. METHODS A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH). To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat (STR) markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene. RESULTS By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them, c.1304A>C was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype. This, c.1304A>C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435 (p.D435A) of its protein product. Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic. CONCLUSION The identification of c.1304A>C pathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is the first example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment. PMID:27275418

  18. Consanguineous Marriage and Marital Adjustment in Turkey.

    ERIC Educational Resources Information Center

    Fisiloglu, Hurol

    2001-01-01

    Investigates the relationship between consanguineous marriage and marital adjustment in Turkey. The results of the study show that the consanguineous marriage group had significantly lower marital adjustment and had more conflict with extended family than the nonconsanguineous marriage group. The finding is discussed in the context of research and…

  19. A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family.

    PubMed

    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

    2013-07-01

    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.

  20. A Homozygous TPO Gene Duplication (c.1184_1187dup4) Causes Congenital Hypothyroidism in Three Siblings Born to a Consanguineous Family.

    PubMed

    Cangul, Hakan; Aydin, Banu K; Bas, Firdevs

    2015-12-01

    Congenital hypothyroidism (CH) is the most common neonatal endocrine disease, and germ-line mutations in the TPO gene cause the inherited form of the disease. Our aim in this study was to determine the genetic basis of congenital hypothyroidism in three affected children coming from a consanguineous Turkish family. Because CH is usually inherited in autosomal recessive manner in consanguineous/multicase families, we adopted a two-stage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First, we investigated the potential genetic linkage of the family to any known CH locus, using microsatellite markers, and then screened for mutations in linked-gene by conventional sequencing. The family showed potential linkage to the TPO gene and we detected a homozygous duplication (c.1184_1187dup4) in all cases. The mutation segregated with disease status in the family. This study confirms the pathogenicity of the c.1184_1187dup4 mutation in the TPO gene and helps establish a genotype/phenotype correlation associated with this mutation. It also highlights the importance of molecular genetic studies in the definitive diagnosis and accurate classification of CH. PMID:27617131

  1. Novel homozygous mutations in the EVC and EVC2 genes in two consanguineous families segregating autosomal recessive Ellis-van Creveld syndrome.

    PubMed

    Aziz, Abdul; Raza, Syed I; Ali, Salman; Ahmad, Wasim

    2016-01-01

    Ellis-van Creveld syndrome (EVC) is a rare developmental disorder characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails, teeth, oral and cardiac abnormalities. It is caused by biallelic mutations in the EVC or EVC2 gene, separated by 2.6 kb of genomic sequence on chromosome 4p16. In the present study, we have investigated two consanguineous families of Pakistani origin, segregating EVC in autosomal recessive manner. Linkage in the families was established to chromosome 4p16. Subsequently, sequence analysis identified a novel nonsense mutation (p.Trp234*) in exon 8 of the EVC2 gene and 15 bp duplication in exon 14 of the EVC gene in the two families. This further expands the mutations in the EVC or EVC2 genes resulting in the EVC syndrome.

  2. Hereditary tyrosinaemia type II in a consanguineous Ashkenazi Jewish family: intrafamilial variation in phenotype; absence of parental phenotype effects on the fetus.

    PubMed

    Chitayat, D; Balbul, A; Hani, V; Mamer, O A; Clow, C; Scriver, C R

    1992-01-01

    We describe an Ashkenazi Jewish family in which two adults, offspring of consanguineous parents, have persistent hypertyrosinaemia (770-1110 mumol/L; normal less than 110 mumol/L). The metabolic disorder in this family is apparently due to hepatic cytosolic tyrosine aminotransferase deficiency (hereditary tyrosinaemia, type II; McKusick, 276600), because it is associated with the oculocutaneous manifestations of Richner-Hanhart syndrome. The association of this syndrome with hereditary tyrosinaemia type II is presumed to be constant. It is not in this family. The affected female sib (age 41 years) has hypertyrosinaemia and oculocutaneous signs; the brother (age 39 years) has hypertyrosinemia but no oculocutaneous disease. Both sibs have two children; none has signs of a metabolic fetopathy. Maternal hypertyrosinaemia and maternal hyperphenylalaninaemia evidently constitute different risk factors for the fetus. Paternal hypertyrosinaemia is apparently not a risk to male infertility.

  3. The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome

    PubMed Central

    Sheridan, Molly B.; Wohler, Elizabeth; Batista, Denise A. S.; Applegate, Carolyn; Hoover-Fong, Julie

    2015-01-01

    Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome. DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism. DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions of DCAF17 in the proband revealed homozygosity for a previously described founder mutation (c.436delC). Targeted DCAF17 sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified. PMID:26664771

  4. [Consanguineous marriage in Turkey and its effects on infant mortality].

    PubMed

    Ulusoy, M; Tuncbilek, E

    1987-01-01

    The authors examine the effects of consanguineous marriage on infant mortality in Turkey. An attempt is made to distinguish the influence of consanguineous marriage from that of selected regional and socioeconomic factors. It is found that "the differences of the average infant mortality rates between consanguineous and non-consanguineous marriages are parallel to the development differences between the regions as well as the conditions of the house which are thought to signify the socioeconomic differences. Although the differences in averages are insignificant statistically, this trend [indicates] that consanguineous marriages [affect] infant mortality." Data are from the 1983 Turkish Fertility, Contraceptive Prevalence and Family Health Status Survey. (SUMMARY IN ENG)

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

    PubMed Central

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

    2012-01-01

    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. PMID:23233793

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

    PubMed Central

    German, J; Roe, A M; Leppert, M F; Ellis, N A

    1994-01-01

    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 chi 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 "reverse" genetics definition of the primary defect in Bloom syndrome. Images PMID:8022833

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

    SciTech Connect

    German, J.; Roe, A.M.; Ellis, N.A. ); Leppert, M.F. )

    1994-07-05

    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.

  8. Homozygous p.G61E mutation in a consanguineous Pakistani family with co-existence of juvenile-onset open angle glaucoma and primary congenital glaucoma.

    PubMed

    Bashir, Rasheeda; Tahir, Hafsa; Yousaf, Khazeema; Naz, Shagufta; Naz, Sadaf

    2015-10-10

    Glaucoma is one of the primary causes of visual impairment and blindness in the world. It is characterized by the damage to the optic nerve head and visual field loss. Variants in CYP1B1 are the most common cause of glaucoma in different world populations. We studied a consanguineous Pakistani family in which three affected individuals had a severe form of glaucoma with members in one generation diagnosed with juvenile-onset open angle glaucoma at 27 years of age, while the members of the next generation were affected with primary congenital glaucoma with onset at birth. Sequencing of CYP1B1 revealed a homozygous transition variant, c.182G>A, p.G61E which co-segregated with the disease phenotype. This variant has been previously reported to cause both recessively and dominantly inherited PCG and JOAG in different populations. However, this reported for the first time in Pakistani PCG and JOAG patients in a homozygous state. This is also the first ever report of a CYP1B1 variant segregating in a consanguineous family with co-existence of JOAG and PCG in two subsequent generations. This observation of different phenotypes due to an identical mutation suggests that primary congenital glaucoma and juvenile-onset open angle glaucoma can both be caused by homozygosity for the same mutation. It also indicates the reduced penetrance of the variant in those affected due to p.G61E mutation and further implies that modifiers have a role in controlling the time of onset of the disorder.

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

    ERIC Educational Resources Information Center

    Santos, Silvana; Bizzo, Nelio

    2005-01-01

    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…

  10. The effect of consanguinity on neonatal outcomes and health.

    PubMed

    Abbas, Hussein A; Yunis, Khalid

    2014-01-01

    Consanguineous marriages constitute a significant fraction of marriages worldwide and confer a major public health concern on newborns. In addition to the risk of acquiring a recessive genetic disease, the offspring of consanguineous parents are plausibly at an increased risk of preterm birth, decreased anthropometric measurements, congenital defects and mortality. How consanguinity confers such an increased risk is still largely unknown. In this review, we discuss the effect of consanguinity on selected gestational outcomes by delineating the different studies that have led to such findings. We also investigate the different conclusions that have emerged regarding the effect of consanguinity on gestational outcomes. PMID:25060272

  11. Clinical and molecular effect on offspring of a marriage of consanguineous spinocerebellar ataxia type 7 mutation carriers: a family case report.

    PubMed

    Magaña, Jonathan J; Tapia-Guerrero, Yessica S; Velázquez-Pérez, Luis; Cruz-Mariño, Tania; Cerecedo-Zapata, Cesar M; Gómez, Rocío; Murillo-Melo, Nadia M; González-Piña, Rigoberto; Hernández-Hernández, Oscar; Cisneros, Bulmaro

    2014-01-01

    Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder characterized by degeneration of the cerebellum, brainstem, and retina that is caused by abnormal expansion of a CAG repeat located in the ATXN7 gene encoding sequence on chromosome 3p21.1. Although SCA7 is an uncommon autosomal dominant ataxia, we previously found increased prevalence of the disease in a Southeastern Mexican population. In this study, we described to our knowledge for the first time a marriage of consanguineous SCA7 mutation carriers and their offspring effect. We characterized a severely affected infantile-onset female patient whose parents and two siblings exhibited no symptoms of the disease at time of diagnosis. A comprehensive clinical analysis of the proband showed a progressive cerebellar syndrome, including gait ataxia, movement disorders, and saccadic movements, as well as hyperreflexia, visual deterioration, urinary and cardiovascular dysfunction, and impaired nerve conduction. The SCA7 mutation was detected in the proband patient. Subsequently, genetic examination using four ATXN7 gene-linked markers (three centromeric microsatellite markers [D3S1228, D3S1287, and D3S3635] and an intragenic Single Nucleotide Polymorphism [SNP-3145G/A]) revealed that the proband descends from a couple of consanguineous SCA7 mutation carriers. Genotyping analysis demonstrated that all offspring inherited only one mutant allele, and that the severe infantile-onset phenotype is caused by germinal expansion (from 37 to 72 CAG repeats) of the paternal mutant allele. Interestingly, the couple also referred a miscarriage. Finally, we found no CAA interruptions in the ATXN7 gene CAG repeats tract in this family, which might explain, at least in part, the triplet instability in the proband.

  12. Clinical and molecular effect on offspring of a marriage of consanguineous spinocerebellar ataxia type 7 mutation carriers: a family case report

    PubMed Central

    Magaña, Jonathan J; Tapia-Guerrero, Yessica S; Velázquez-Pérez, Luis; Cruz-Mariño, Tania; Cerecedo-Zapata, Cesar M; Gómez, Rocío; Murillo-Melo, Nadia M; González-Piña, Rigoberto; Hernández-Hernández, Oscar; Cisneros, Bulmaro

    2014-01-01

    Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder characterized by degeneration of the cerebellum, brainstem, and retina that is caused by abnormal expansion of a CAG repeat located in the ATXN7 gene encoding sequence on chromosome 3p21.1. Although SCA7 is an uncommon autosomal dominant ataxia, we previously found increased prevalence of the disease in a Southeastern Mexican population. In this study, we described to our knowledge for the first time a marriage of consanguineous SCA7 mutation carriers and their offspring effect. We characterized a severely affected infantile-onset female patient whose parents and two siblings exhibited no symptoms of the disease at time of diagnosis. A comprehensive clinical analysis of the proband showed a progressive cerebellar syndrome, including gait ataxia, movement disorders, and saccadic movements, as well as hyperreflexia, visual deterioration, urinary and cardiovascular dysfunction, and impaired nerve conduction. The SCA7 mutation was detected in the proband patient. Subsequently, genetic examination using four ATXN7 gene-linked markers (three centromeric microsatellite markers [D3S1228, D3S1287, and D3S3635] and an intragenic Single Nucleotide Polymorphism [SNP-3145G/A]) revealed that the proband descends from a couple of consanguineous SCA7 mutation carriers. Genotyping analysis demonstrated that all offspring inherited only one mutant allele, and that the severe infantile-onset phenotype is caused by germinal expansion (from 37 to 72 CAG repeats) of the paternal mutant allele. Interestingly, the couple also referred a miscarriage. Finally, we found no CAA interruptions in the ATXN7 gene CAG repeats tract in this family, which might explain, at least in part, the triplet instability in the proband. PMID:25664129

  13. A new locus on chromosome 22q13.31 linked to recessive genetic epilepsy with febrile seizures plus (GEFS+) in a Tunisian consanguineous family

    PubMed Central

    2013-01-01

    Background Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. The aim of our study was to identify the responsible locus for GEFS+ syndrome in a consanguineous Tunisian family showing three affected members, by carrying out a genome-wide single nucleotide polymorphisms (SNPs) genotyping followed by a whole-exome sequencing. We hypothesized an autosomal recessive (AR) mode of inheritance. Results Parametric linkage analysis and haplotype reconstruction identified a new unique identical by descent (IBD) interval of 527 kb, flanking by two microsatellite markers, 18GTchr22 and 15ACchr22b, on human chromosome 22q13.31 with a maximum multipoint LOD score of 2.51. Our analysis was refined by the use of a set of microsatellite markers. We showed that one of them was homozygous for the same allele in all affected individuals and heterozygous in healthy members of this family. This microsatellite marker, we called 17ACchr22, is located in an intronic region of TBC1D22A gene, which encodes a GTPase activator activity. Whole-exome sequencing did not reveal any mutation on chromosome 22q13.31 at the genome wide level. Conclusions Our findings suggest that TBC1D22A is a new locus for GEFS+. PMID:24067191

  14. Consanguineous marriage among the Fulani.

    PubMed

    Hampshire, K R; Smith, M T

    2001-08-01

    The Fulani are a broad ethnic category of nomadic and seminomadic pastoralists and agropastoralists living in the semiarid Sahel region of sub-Saharan Africa. The Fulani are patrilineal, patrilocal, and moderately polygynous, with arranged first marriages accompanied by the payment of bridewealth, ideally in the form of cattle. Consanguineous marriage is frequent, with first or second cousin marriage preferred. In this paper we present data on levels of consanguineous marriage among the Fulani of northern Burkina Faso and test the hypothesis that inbreeding may be more frequent when there is a scarcity of cattle available, since bridewealth demands are thought to be reduced with close-kin marriage. Among 308 women's marriages, 203 (65.8%) were between kin up to and including second cousins, and 102 (33.1%) were between nonkin. Among 276 men's marriages, 196 (71.0%) were between kin up to and including second cousins, and 77 (27.9%) were between nonkin. The mean population inbreeding coefficient (alpha) was 0.0355 for women, and 0.0374 for men. No increase was found in population levels of inbreeding estimated from marriages contracted after the droughts of 1973 and 1984, which drastically reduced the Fulani's cattle stocks. However, a significantly higher rate of consanguineous marriage was found in families owning the fewest cattle.

  15. Novel SIL1 nonstop mutation in a Chinese consanguineous family with Marinesco-Sjögren syndrome and Dandy-Walker syndrome.

    PubMed

    Gai, Nan; Jiang, Chen; Zou, Yong-Yi; Zheng, Yu; Liang, De-Sheng; Wu, Ling-Qian

    2016-07-01

    Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder, which is characterized by congenital cataracts, cerebellar ataxia, progressive muscle weakness, and delayed psychomotor development. SIL1, which is located at 5q31.2, is the only gene known to cause MSS. Dandy-Walker syndrome (DWS) is defined by hypoplasia, upward rotation of the cerebellar vermis, and cystic dilation of the fourth ventricle; however, its genetic pathogeny remains unclear. Here, we report a Chinese consanguineous family with MSS and DWS. Whole exome sequencing identified a novel nonstop mutation in SIL1. Sanger sequencing revealed that the mutation was segregated in this family according to a recessive mode of inheritance. We found that the mutation changed a stop codon (TGA) to an arginine codon (CGA), and no in-frame termination codon in the 3' untranslated region (UTR) of SIL1 could be found. The mRNA levels of SIL1 were decreased by 56.6% and 37.5% in immortalized lymphoblasts of the patients respectively; the protein levels of SIL1 were substantially decreased. This case study is the first report on Chinese MSS patients, MSS complicated by DWS, and a nonstop mutation in SIL1. Our findings imply the pathogenetic association between DWS and MSS.

  16. Novel SIL1 nonstop mutation in a Chinese consanguineous family with Marinesco-Sjögren syndrome and Dandy-Walker syndrome.

    PubMed

    Gai, Nan; Jiang, Chen; Zou, Yong-Yi; Zheng, Yu; Liang, De-Sheng; Wu, Ling-Qian

    2016-07-01

    Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder, which is characterized by congenital cataracts, cerebellar ataxia, progressive muscle weakness, and delayed psychomotor development. SIL1, which is located at 5q31.2, is the only gene known to cause MSS. Dandy-Walker syndrome (DWS) is defined by hypoplasia, upward rotation of the cerebellar vermis, and cystic dilation of the fourth ventricle; however, its genetic pathogeny remains unclear. Here, we report a Chinese consanguineous family with MSS and DWS. Whole exome sequencing identified a novel nonstop mutation in SIL1. Sanger sequencing revealed that the mutation was segregated in this family according to a recessive mode of inheritance. We found that the mutation changed a stop codon (TGA) to an arginine codon (CGA), and no in-frame termination codon in the 3' untranslated region (UTR) of SIL1 could be found. The mRNA levels of SIL1 were decreased by 56.6% and 37.5% in immortalized lymphoblasts of the patients respectively; the protein levels of SIL1 were substantially decreased. This case study is the first report on Chinese MSS patients, MSS complicated by DWS, and a nonstop mutation in SIL1. Our findings imply the pathogenetic association between DWS and MSS. PMID:27106665

  17. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity

    PubMed Central

    Halbritter, Jan; Gee, Heon Yung; Porath, Jonathan D.; Lawson, Jennifer A.; Airik, Rannar; Shril, Shirlee; Allen, Susan J.; Stein, Deborah; Al Kindy, Adila; Beck, Bodo B.; Cengiz, Nurcan; Moorani, Khemchand N.; Ozaltin, Fatih; Hashmi, Seema; Sayer, John A.; Bockenhauer, Detlef; Soliman, Neveen A.; Otto, Edgar A.; Lifton, Richard P.; Hildebrandt, Friedhelm

    2015-01-01

    Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering, and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis and allows identification of novel candidate genes. PMID:26489029

  18. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.

    PubMed

    Braun, Daniela A; Schueler, Markus; Halbritter, Jan; Gee, Heon Yung; Porath, Jonathan D; Lawson, Jennifer A; Airik, Rannar; Shril, Shirlee; Allen, Susan J; Stein, Deborah; Al Kindy, Adila; Beck, Bodo B; Cengiz, Nurcan; Moorani, Khemchand N; Ozaltin, Fatih; Hashmi, Seema; Sayer, John A; Bockenhauer, Detlef; Soliman, Neveen A; Otto, Edgar A; Lifton, Richard P; Hildebrandt, Friedhelm

    2016-02-01

    Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes. PMID:26489029

  19. [Consanguinity and congenital abnormalities].

    PubMed

    Søgaard, Marie; Vedsted-Jakobsen, Agnete

    2003-04-28

    Knowledge of consanguinity is relevant for employees in the Danish national health service, since about 7.5% of the Danish population has another ethnic background than Danish and the majority comes from cultures where consanguineous marriages are not unusual. In the literature it is found that consanguineous couples have a higher risk of having children with congenital malformations. The risk is increased by a factor 2 to 2 1/2. The average risk in Denmark is about 3%. Primarily, the autosomal recessive diseases are expressed in children with consanguineous parents. In order to advise and diagnose it is essential to clarify the consanguinity state. In case of pregnancy with consanguineous parents, we recommend: 1) Counselling to estimate the risk of foetal illness and information about possible examination possibilities. 2) An ultrasound scan at the gestational age of 11-14 weeks in order to measure nuchal translucency and an early malformation scan. 3) An ultrasound scan for malformations at the gestational age of 18-20 weeks. 4) An ultrasound scan especially in order to detect foetal heart malformations at the gestational age of 20-24 weeks.

  20. Effects of consanguineous marriage on reproductive outcome in an Arab community in Israel.

    PubMed

    Jaber, L; Merlob, P; Gabriel, R; Shohat, M

    1997-12-01

    Intrafamilial marriage is favoured by the Arab community in Israel, almost all of whom live in villages populated by a few (< 20) founding families. A previous study in Taibe, a large Arab village located 30 km from Tel Aviv, showed a significantly high malformation rate among infants of consanguineous parents. The present study examines the reproductive consequences of parental consanguinity in 610 families from the same village, selected retrospectively through infants routinely seen in the local well baby clinic. All mothers were interviewed with regard to previous pregnancy outcomes, including abortions, stillbirths, and neonatal or infant deaths, as well as the degree of consanguinity. In addition, we analysed the anthropometric measurements of the probands. The incidence of infant deaths was significantly higher in the inbred group (p < 0.001). No significant increase in fetal loss between the inbred and outbred groups was observed. There were no differences in anthropometric features, except for a lower birth weight in the consanguineous group (p < 0.035). This study, combined with our previous studies of the same population, indicates a prominent public health problem associated with consanguineous marriage in the Arab community and a need for specific genetic counselling.

  1. Sociodemographic correlates of consanguineous marriage in the Muslim population of India.

    PubMed

    Hussain, R; Bittles, A H

    2000-10-01

    Using data derived from the 1992-1993 National Family Health Survey, the sociodemographic characteristics of consanguineous marriage were determined in the Muslim population of India. In this nationally representative sample of 8436 women, consanguineous marriages accounted for 22.0% of the total. No differences between the consanguineous and non-consanguineous groups were observed in terms of mean age at marriage or mean age at cohabitation. The study confirmed the negative association between consanguineous marriage and maternal education but also indicated that women in consanguineous unions were more likely to be employed, albeit mainly in agricultural work on behalf of the family. Consanguineous couples more frequently lived in smaller towns and in an extended family environment. Somewhat conflicting results were obtained with indicators of socioeconomic status, but the overall picture suggested that consanguineous households had greater access to consumer goods because of their larger number of co-resident persons.

  2. Comments on "Consanguineous Marriages in Pakistan".

    PubMed

    Hakim, A

    1994-01-01

    Some critical comments are made on a paper entitled "Consanguineous Marriages in Pakistan." Most studies have considered early age at marriage, rural or extended family setup and low socioeconomic status when investigating the issue. The background demographic variables and behavioral aspects of consanguinity were studied only by a few, therefore a lack of data exists on pertinent social, cultural, and behavioral dynamics. In Pakistan over 60% of marriages are between first or second cousins. The highest rates of such marriages have been reported in rural areas, among individuals with low educational level, and among the poorest. However, cousin unions are also common among landowning families. In addition to socioeconomic reasons, these marriages are socially acceptable because they facilitate prenuptial negotiations and provide more compatibility between the husband and wife as well as the bride and the mother-in-law. The evidence on consanguinity and fertility is conflicting. The effect of inbreeding on fertility has been demonstrated by most studies. The effect of consanguinity on mortality is also wrought with ambiguities because of methodological flaws. Although the present authors used limited bivariate analysis, they could not account for increased fertility and mortality in consanguineous matings by examining socioeconomic differences and background demographic variables. There is a need to indicate clearly to what extent the genetic effect is responsible for the excess fertility and mortality after controlling for maternal, sociodemographic, and behavioral characteristics. The article made a contribution to elucidating the impact of cousin marriages, a well entrenched custom, on fertility, mortality, and the status of women.

  3. Integration of sequence data from a Consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene.

    PubMed

    Okada, Yukinori; Diogo, Dorothee; Greenberg, Jeffrey D; Mouassess, Faten; Achkar, Walid A L; Fulton, Robert S; Denny, Joshua C; Gupta, Namrata; Mirel, Daniel; Gabriel, Stacy; Li, Gang; Kremer, Joel M; Pappas, Dimitrios A; Carroll, Robert J; Eyler, Anne E; Trynka, Gosia; Stahl, Eli A; Cui, Jing; Saxena, Richa; Coenen, Marieke J H; Guchelaar, Henk-Jan; Huizinga, Tom W J; Dieudé, Philippe; Mariette, Xavier; Barton, Anne; Canhão, Helena; Fonseca, João E; de Vries, Niek; Tak, Paul P; Moreland, Larry W; Bridges, S Louis; Miceli-Richard, Corinne; Choi, Hyon K; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Raj, Towfique; De Jager, Philip L; Raychaudhuri, Soumya; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Siminovitch, Katherine A; Gregersen, Peter K; Mardis, Elaine R; Arayssi, Thurayya; Kazkaz, Layla A; Plenge, Robert M

    2014-01-01

    Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2 × 10(-6)). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted.

  4. Profiling β Thalassemia Mutations in Consanguinity and Nonconsanguinity for Prenatal Screening and Awareness Programme.

    PubMed

    Kumar, Ravindra; Arya, Vandana; Agarwal, Sarita

    2015-01-01

    Mutation spectrum varies significantly in different parts and different ethnic groups of India. Social factors such as preference to marry within the community and among 1st degree relatives (consanguinity) play an important role in impeding the gene pool of the disease within the community and so in society by and large. The present paper discusses the role of consanguinity in profiling of beta thalassemia mutation, and thus the approach for prenatal screening and prevention based awareness programme. Clinically diagnosed 516 cases of beta thalassemia were screened at molecular level. A detailed clinical Proforma was recorded with the information of origin of the family, ethnicity, and consanguinity. The present study reports that subjects originating from Uttar Pradesh, Uttarakhand, Bihar, and Jharkhand have c.92+5G>C and c.124_127delTTCT mutation as the commonest mutation compared to the subjects hailing from Madhya Pradesh and Chhattisgarh and Nepal where sickle mutation was found more common. In 40 consanguineous unions more common and specific beta mutations with higher rate of homozygosity have been reported. This consanguinity-based data helps not only in deciding target oriented prenatal diagnostic strategies but also in objective based awareness programmes in prevention of thalassemia major birth. PMID:26576156

  5. Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions

    PubMed Central

    Shihab, Hashem A.; Rodriguez, Santiago; Gaunt, Tom R.; Day, Ian N.M.

    2016-01-01

    Summary Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome—even when completely “knocked out,” do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations “as a whole” can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. PMID:27000383

  6. Consanguineous marriages in Afghanistan.

    PubMed

    Saify, Khyber; Saadat, Mostafa

    2012-01-01

    The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among Afghanistan populations. Data on types of marriages were collected using a simple questionnaire. The total number of couples in the study was 7140 from the following provinces: Badakhshan, Baghlan, Balkh, Bamyan, Kabul, Kunduz, Samangan and Takhar. Consanguineous marriages were classified by the degree of relationship between couples: double first cousins, first cousins, first cousins once removed, second cousins and beyond second cousins. The coefficient of inbreeding (F) was calculated for each couple and the mean coefficient of inbreeding (α) estimated for each population. The proportion of consanguineous marriages in the country was 46.2%, ranging from 38.2% in Kabul province to 51.2% in Bamyan province. The equivalent mean inbreeding coefficient (α) was 0.0277, and ranged from 0.0221 to 0.0293 in these two regions. There were significant differences between provinces for frequencies of different types of marriages (p<0.001). First cousin marriages (27.8%) were the most common type of consanguineous marriages, followed by double first cousin (6.9%), second cousin (5.8%), beyond second cousin (3.9%) and first cousin once removed (1.8%). There were significant differences between ethnic groups for the types of marriages (χ2=177.6, df=25, p<0.001). Tajiks (Soni) and Turkmens (also Pashtuns) showed the lowest (α=0.0250) and highest (α=0.0297) mean inbreeding coefficients, respectively, among the ethnic groups in Afghanistan. The study shows that Afghanistan's populations, like other Islamic populations, have a high level of consanguinity.

  7. Consanguineous Iranian kindreds with severe Tourette syndrome.

    PubMed

    Motlagh, Maria G; Seddigh, Arshia; Dashti, Behnoosh; Leckman, James F; Alaghband-Rad, Javad

    2008-10-30

    The search for vulnerability genes for Tourette syndrome has been ongoing for nearly three decades. The contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. Homozygosity mapping has been successfully used to detect recessive loci within populations with high rates of consanguinity. Using this technique, even quite small inbred families can be informative due to autozygosity in which the two alleles at an autosomal locus are identical by descent (i.e., copies of a single ancestral gene). To explore the utility of this approach, we identified 12 consanguineous Iranian families. Remarkably, these families were seen with an unusual natural history characterized by the early onset of vocal tics and coprolalia and frequent comorbidity with obsessive-compulsive disorder. Genotyping the affected and unaffected members of these pedigrees has the potential to identify rare recessive contributions to this disorder.

  8. Community perceptions of reasons for preference for consanguineous marriages in Pakistan.

    PubMed

    Hussain, R

    1999-10-01

    Although the recent Pakistan Demographic and Health Survey (DHS) show that two-thirds of marriages in Pakistan are consanguineous, the sociocultural determinants of such marriages remain largely unexplored. This paper examines the relative importance of the three commonly perceived reasons for such marriages: religious, economic and cultural. The analysis is based on qualitative data collected in 1995 from multi-ethnic and multi-religious communities in Karachi, the largest city of Pakistan. Results show that consanguineous marriages are preferred across all ethnic and religious groups to a varying degree, and that parents continue to be the prime decision-makers for marriages of both sons and daughters. The major reasons for a preference for consanguineous marriages are sociocultural rather than any perceived economic benefits, either in the form of consolidation of family property or smaller and less expensive dowries. Among Muslims, following religious traditions is the least commonly cited reason for such marriages. Despite the reported sociocultural advantages of consanguineous marriages, such unions are perceived to be exploitative as they perpetuate the existing power structures within the family. PMID:10581876

  9. Consanguineous marriages, pearls and perils: Geneva International Consanguinity Workshop Report.

    PubMed

    Hamamy, Hanan; Antonarakis, Stylianos E; Cavalli-Sforza, Luigi Luca; Temtamy, Samia; Romeo, Giovanni; Kate, Leo P Ten; Bennett, Robin L; Shaw, Alison; Megarbane, Andre; van Duijn, Cornelia; Bathija, Heli; Fokstuen, Siv; Engel, Eric; Zlotogora, Joel; Dermitzakis, Emmanouil; Bottani, Armand; Dahoun, Sophie; Morris, Michael A; Arsenault, Steve; Aglan, Mona S; Ajaz, Mubasshir; Alkalamchi, Ayad; Alnaqeb, Dhekra; Alwasiyah, Mohamed K; Anwer, Nawfal; Awwad, Rawan; Bonnefin, Melissa; Corry, Peter; Gwanmesia, Lorraine; Karbani, Gulshan A; Mostafavi, Maryam; Pippucci, Tommaso; Ranza-Boscardin, Emmanuelle; Reversade, Bruno; Sharif, Saghira M; Teeuw, Marieke E; Bittles, Alan H

    2011-09-01

    Approximately 1.1 billion people currently live in countries where consanguineous marriages are customary, and among them one in every three marriages is between cousins. Opinions diverge between those warning of the possible health risks to offspring and others who highlight the social benefits of consanguineous marriages. A consanguinity study group of international experts and counselors met at the Geneva International Consanguinity Workshop from May 3, 2010, to May 7, 2010, to discuss the known and presumptive risks and benefits of close kin marriages and to identify important future areas for research on consanguinity. The group highlighted the importance of evidence-based counseling recommendations for consanguineous marriages and of undertaking both genomic and social research in defining the various influences and outcomes of consanguinity. Technological advances in rapid high-throughput genome sequencing and for the identification of copy number variants by comparative genomic hybridization offer a significant opportunity to identify genotype-phenotype correlations focusing on autozygosity, the hallmark of consanguinity. The ongoing strong preferential culture of close kin marriages in many societies, and among migrant communities in Western countries, merits an equivalently detailed assessment of the social and genetic benefits of consanguinity in future studies.

  10. Science and society: genetic counselling and customary consanguineous marriage.

    PubMed

    Modell, Bernadette; Darr, Aamra

    2002-03-01

    Consanguineous marriage is customary in many societies, but leads to an increased birth prevalence of infants with severe recessive disorders. It is therefore often proposed that consanguineous marriage should be discouraged on medical grounds. However, several expert groups have pointed out that this proposal is inconsistent with the ethical principles of genetic counselling, overlooks the social importance of consanguineous marriage and is ineffective. Instead, they suggest that the custom increases the possibilities for effective genetic counselling, and recommend a concerted effort to identify families at increased risk, and to provide them with risk information and carrier testing when feasible.

  11. From new genetics to everyday knowledge: Ideas about how genetic diseases are transmitted in two large Brazilian families

    NASA Astrophysics Data System (ADS)

    Santos, Silvana; Bizzo, Nelio

    2005-07-01

    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 with a neurodegenerative disorder, SPOAN syndrome (spastic paraplegia, optic atrophy and neuropathy), and 40 individuals of another family living with neurofibromatosis type 1 (NF1). The results indicate that families here studied have built narratives to explain the origin of genetic diseases, saying that an ancestor infected with syphilis gave rise to disorders and birthmarks transmitted to descendents.

  12. Consanguineous marriage in Jordan.

    PubMed

    Khoury, S A; Massad, D

    1992-07-15

    We conducted a population-based study of consanguineous marriages in Jordan. About two thousand households were interviewed. First cousin marriages were encountered in 32.03%, second cousin in 6.8%, distant relation in 10.5%, and no relation in 50% of all marriages, respectively. Inbreeding coefficients were compared with those of other countries. The most important variables affecting inbreeding were social tradition, religion, education, and place of residence--urban vs. rural. Secular trends appear rather stable since the early decades of the twentieth century, especially for first cousin marriages. Jordan society showed a deeply rooted traditional behavioral pattern when inbreeding is considered.

  13. Organ donation consanguinity or universality.

    PubMed

    Kishore, R R

    1996-01-01

    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.

  14. Organ donation consanguinity or universality.

    PubMed

    Kishore, R R

    1996-01-01

    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

  15. An analysis of consanguineous marriage in the Muslim population of India at regional and state levels.

    PubMed

    Bittles, A H; Hussain, R

    2000-01-01

    Consanguineous marriage is widely favoured in a large majority of the world's Islamic populations. According to recent estimates, the resident Muslim population of India is over 100 million. However, apart from a few numerically small or geographically defined surveys, little is known about their patterns of marriage preferences since partition of the Indian Subcontinent in 1947. This study seeks to determine the prevalence and patterns of consanguineous marriages contracted among Indian Muslims at regional and state levels during the last two generations. Data from the 1992/93 Indian National Family Health Survey (NFHS) were used in the analysis. The NFHS was a nationally-representative survey of ever-married women aged 13-49 years, conducted across 25 states of India. Of the initial 9845 respondents, 8436 were included in the final weighted analysis sample. Overall, 22.0% of marriages were found to be contracted between spouses related as second cousins or closer, ranging from 15.9% in the eastern states to 32.9% in the western states of India. In all parts of the country first cousin marriages were the preferred form of consanguineous union, and in four of the five regions paternal first cousin marriages predominated. Despite predictions to the contrary, there was no evidence of a significant change in the prevalence of consanguineous unions over the course of the study period, which extended from the late 1950s to the early 1990s.

  16. An analysis of consanguineous marriage in the Muslim population of India at regional and state levels.

    PubMed

    Bittles, A H; Hussain, R

    2000-01-01

    Consanguineous marriage is widely favoured in a large majority of the world's Islamic populations. According to recent estimates, the resident Muslim population of India is over 100 million. However, apart from a few numerically small or geographically defined surveys, little is known about their patterns of marriage preferences since partition of the Indian Subcontinent in 1947. This study seeks to determine the prevalence and patterns of consanguineous marriages contracted among Indian Muslims at regional and state levels during the last two generations. Data from the 1992/93 Indian National Family Health Survey (NFHS) were used in the analysis. The NFHS was a nationally-representative survey of ever-married women aged 13-49 years, conducted across 25 states of India. Of the initial 9845 respondents, 8436 were included in the final weighted analysis sample. Overall, 22.0% of marriages were found to be contracted between spouses related as second cousins or closer, ranging from 15.9% in the eastern states to 32.9% in the western states of India. In all parts of the country first cousin marriages were the preferred form of consanguineous union, and in four of the five regions paternal first cousin marriages predominated. Despite predictions to the contrary, there was no evidence of a significant change in the prevalence of consanguineous unions over the course of the study period, which extended from the late 1950s to the early 1990s. PMID:10768421

  17. Consanguineous marriage among rural Arabs in Israel.

    PubMed

    Freundlich, E; Hino, N

    1984-11-01

    The prevalence of consanguineous marriages was examined among the Arab rural population in the Western Galilee region in Israel. The survey was conducted by questioning women attending Mother and Child Health Centers, or those met on the main street of the village. The overall figures were unusually high (39%), including those for first and second cousins. They were highest in the Druze population (49%), lower in the Moslems (40%) and still lower in the Christians (29%) (P less than 0.001). The most common type was first-cousin marriages, especially where the husband's father and the wife's father were brothers. The prevalence of consanguineous marriages was higher in the younger generation whose members had remained in their family village. These findings indicate that the traditional way of life, with its close family relationships, is still most common in the Arab rural society in Israel. The high prevalence of consanguinity is an unfavorable factor in this population's health condition. It is believed that the present educational and occupational changes will gradually alter this custom.

  18. Consanguinity and increased risk for schizophrenia in Egypt

    PubMed Central

    Mansour, Hader; Fathi, Warda; Klei, Lambertus; Wood, Joel; Chowdari, Kodavali; Watson, Annie; Eissa, Ahmed; Elassy, Mai; Ali, Ibtihal; Salah, Hala; Yassin, Amal; Tobar, Salwa; El-Boraie, Hala; Gaafar, Hanan; Ibrahim, Nahed E.; Kandil, Kareem; El-Bahaei, Wafaa; El-Boraie, Osama; Alatrouny, Mohamed; El-Chennawi, Farha; Devlin, Bernie; Nimgaonkar, Vishwajit L.

    2010-01-01

    Background Consanguinity has been suggested as a risk factor for psychsoses in some Middle Eastern countries, but adequate control data are unavailable. Our recent studies in Egypt have shown elevated parental consanguinity rates among patients with bipolar I disorder (BP1), compared with controls. We have now extended our analyses to Schizophrenia (SZ) in the same population. Methods A case-control study was conducted at Mansoura University Hospital, Mansoura, Egypt (SZ, n = 75; controls, n = 126, and their available parents). The prevalence of consanguinity was estimated from family history data (‘self report’), followed by DNA analysis using short tandem repeat polymorphisms (STRPs, n = 63) (‘DNA-based’ rates). Results Self reported consanguinity was significantly elevated among the patients (SZ: 46.6%, controls: 19.8%, OR 3.53, 95% CI 1.88, 6.64; p = 0.000058, 1 d.f.). These differences were confirmed using DNA based estimates for coefficients of inbreeding (inbreeding coefficients as means ± standard error, cases: 0.058 ± 0.007, controls: 0.022 ± 0.003). Conclusions Consanguinity rates are signifcantly elevated among Egyptian SZ patients in the Nile delta region. The associations are similar to those observed with BP1 in our earlier study. If replicated, the substantial risk associated with consanguinity raises public health concerns. They may also pave the way for gene mapping studies. PMID:20435442

  19. Consanguinity, human evolution, and complex diseases

    PubMed Central

    Bittles, A. H.; Black, M. L.

    2010-01-01

    There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F ≥ 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is ≈3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates. PMID:19805052

  20. Is there a significant trend in prevalence of consanguineous marriage in Tehran? A review of three generations.

    PubMed

    Akrami, Seyed Mohammad; Montazeri, Vahideh; Shomali, Somaieh Rashid; Heshmat, Ramin; Larijani, Bagher

    2009-02-01

    Consanguineous marriage is a common practice in Iran. The present study surveyed the trend in consanguineous marriage across three generations of Iranians. Index cases, consisting of 400 individuals attending the diabetes and osteoporosis clinic in Shariati Hospital, were interviewed. Data on consanguinity status for 1789 marriages within the index cases' families were obtained. Generation 1 consisted of marriages contracted before 1948, Generation 2 consisted of marriages contracted between 1949 and 1978, and Generation 3 consisted of marriages contracted after 1979. Prevalence of consanguineous marriage within these three generations was 8.8%, 16.6% and 19%, respectively, and represented a significant trend (p < 0.001). First cousin marriage was the most common type of consanguinity (69%). Socioeconomic level of families was not significantly related to having a consanguineous marriage. These data suggest that premarital genetic counseling and mass media efforts are needed to increase public awareness about genetic risks associated with consanguineous marriage.

  1. The frequency and effecting factors of consanguineous marriage in a group of soldiers in Ankara.

    PubMed

    Kir, Tayfun; Güleç, Mahir; Bakir, Bilal; Hoşjgönül, Esat; Tümerdem, Nazmi

    2005-07-01

    This cross-sectional study was carried out to investigate the frequency of consanguineous marriage in a group of army conscripts in Ankara and the factors affecting this. Of 4153 soldiers, 387 were married. The rate of marriage between first cousins was found to be 19.1%, and the overall rate of consanguineous marriage was 24.1%. Consanguineous marriage was found to be significantly prevalent among soldiers who were born in and still living in the Eastern region; among those who lived in villages; among those whose parents as well as themselves had low educational levels; and among those whose marriages were arranged by their families. Neither the payment of bride-price nor the presence of consanguinity between parents was a significant factor for consanguineous marriage. In addition, the age of the soldier and the age at marriage were significantly lower among soldiers married to first cousins than among soldiers whose marriages were not consanguineous.

  2. Consanguinity Protecting Effect Against Breast Cancer among Tunisian Women: Analysis of BRCA1 Haplotypes.

    PubMed

    Medimegh, Imen; Troudi, Wafa; Omrane, Ines; Ayari, Hajer; Uhrhummer, Nancy; Majoul, Hamdi; Benayed, Farhat; Mezlini, Amel; Bignon, Yves-Jean; Sibille, Catherine; Elgaaied, Amel Benammar

    2015-01-01

    The purpose of this study is to assess the effect of consanguinity on breast cancer incidence in Tunisia. We conducted a case-control study to evaluate the involvement of heterozygote and homozygote haplotypes of BRCA1 gene SNPs according to consanguinity among 40 cases of familial breast cancer, 46 cases with sporadic breast cancer and 34 healthy controls. We showed significant difference in consanguinity rate between breast cancer patients versus healthy controls P = 0.001. Distribution of homozygous BRCA1 haplotypes among healthy women versus breast cancer patients was significantly different; p=0.02. Parental consanguinity seems to protect against breast cancer in the Tunisian population. PMID:25987085

  3. Consanguineous marriage within social/occupational class boundaries in Pakistan.

    PubMed

    Shami, S A; Grant, J C; Bittles, A H

    1994-01-01

    Data on patterns of consanguineous marriage were collected from 5340 families resident in eight cities in the Pakistan province of Punjab. To assess whether social and/or occupational class was interacting with consanguinity, information also was obtained on the hereditary qaum to which each family belonged. In the present generation 46.5% of all marriages were contracted at the level of second cousin or closer, with an average coefficient of inbreeding (F) of 0.0286, and the results indicated that in each of the seventeen qaums there was strong preference for marriage to a close biological relative. However, significant differences existed in the distribution of consanguineous marriage by qaum membership, which could interfere with the interpretation of studies into the biological effects of inbreeding. PMID:8200883

  4. Consanguineous marriage within social/occupational class boundaries in Pakistan.

    PubMed

    Shami, S A; Grant, J C; Bittles, A H

    1994-01-01

    Data on patterns of consanguineous marriage were collected from 5340 families resident in eight cities in the Pakistan province of Punjab. To assess whether social and/or occupational class was interacting with consanguinity, information also was obtained on the hereditary qaum to which each family belonged. In the present generation 46.5% of all marriages were contracted at the level of second cousin or closer, with an average coefficient of inbreeding (F) of 0.0286, and the results indicated that in each of the seventeen qaums there was strong preference for marriage to a close biological relative. However, significant differences existed in the distribution of consanguineous marriage by qaum membership, which could interfere with the interpretation of studies into the biological effects of inbreeding.

  5. Consanguinity on Robinson Crusoe Island, an isolated Chilean population.

    PubMed

    Villanueva, Pia; Fernández, Maria A; De Barbieri, Zulema; Palomino, Hernán

    2014-07-01

    The population of Robinson Crusoe Island is estimated at 633 inhabitants. The current population has a common origin from the first eight families who colonized the island at the end of the 19th century. The objective of this study was to determine the rates of consanguinity, the average coefficients of inbreeding, the types of consanguineous marriages and the inbreeding evolution between 1900 and 2000 on the island. All marriages registered on the island, from the last colonization until 2000 (417 in total), were included in the analysis. In addition, extended genealogies were obtained. The consanguinity rate was 14.9% and the average coefficient of inbreeding (α) 54.05 × 10(-4). The most frequent type of consanguineous marriages was between second cousins, followed by first cousins. The average value of the first/second cousin ratio was 1.11. The population of Robinson Crusoe Island has a high rate of inbreeding. The unique characteristic of the island - its small current population, originating from just a few families, with small rate of gene flow - could explain the observed high and increasing consanguinity.

  6. Association studies in consanguineous populations

    SciTech Connect

    Genin, E.; Clerget-Darpous, F.

    1996-04-01

    To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients. 5 refs., 6 figs., 1 tab.

  7. A Novel Aberrant Splice Site Mutation in RAB23 Leads to an Eight Nucleotide Deletion in the mRNA and Is Responsible for Carpenter Syndrome in a Consanguineous Emirati Family

    PubMed Central

    Ben-Salem, S.; Begum, M.A.; Ali, B.R.; Al-Gazali, L.

    2013-01-01

    Carpenter syndrome is caused by mutations in the RAB23 gene that encodes a small GTPase of the Rab subfamily of proteins. Rab proteins are known to be involved in the regulation of cellular trafficking and signal transduction. Currently, only few mutations in RAB23 have been reported in patients with Carpenter syndrome. In this paper, we report the clinical features, molecular and functional analysis of 2 children from an Emirati consanguineous family with this syndrome. The affected children exhibit the typical features including craniosynostosis, typical facial appearance, polysyndactyly, and obesity. Molecular analysis of the RAB23 gene revealed a homozygous mutation affecting the first nucleotide of the acceptor splice site of exon 5 (c.482-1G>A). This mutation affects the authentic mRNA splicing and activates a cryptic acceptor site within exon 5. Thus, the erroneous splicing results in an eight nucleotide deletion, followed by a frameshift and premature termination codon at position 161 (p.V161fsX3). Due to the loss of the C-terminally prenylatable cysteine residue, the truncated protein will probably fail to associate with the target cellular membranes due to the absence of the necessary lipid modification. The p.V161fsX3 extends the spectrum of RAB23 mutations and points to the crucial role of prenylation in the pathogenesis of Carpenter syndrome within this family. PMID:23599695

  8. Consanguineous marriages in the United Arab Emirates.

    PubMed

    al-Gazali, L I; Bener, A; Abdulrazzaq, Y M; Micallef, R; al-Khayat, A I; Gaber, T

    1997-10-01

    This study examines the frequency of consanguineous marriage and the coefficient of inbreeding in the United Arab Emirates (UAE). The study was conducted in Al Ain and Dubai cities between October 1994 and March 1995. A sample of 2033 married UAE females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and the degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (50.5%) with a coefficient of inbreeding of 0.0222. The commonest type of consanguineous marriage was between first cousins (26.2%). Double first cousin marriages were common (3.5%) compared to other populations. The consanguinity rate in the UAE has increased from 39% to 50.5% in one generation. The level of consanguinity was higher in Al Ain (54.2%) than in Dubai (40%).

  9. Prevalence of consanguineous marriages among Iranian Georgians.

    PubMed

    Rafiee, Laleh; Saadat, Mostafa

    2011-01-01

    Consanguineous marriage--marriage between relatives--has received a great deal of attention as a potential risk factor for many adverse health outcomes. The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among Iranian Georgians living in Frydoonshahr (Isfahan province, central Iran). Data on consanguineous marriages were collected using a simple questionnaire. The total number of couples in this study was 646. Consanguineous marriage was classified by the degree of relationship between couples. First cousin marriages (14.2%) were the most common type of consanguineous marriages, followed by second cousin (7.0%), beyond second cousin (1.5%) and first cousin once removed (0.6%). The mean inbreeding coefficient (α) was calculated as 0.0104 for the population. The present study shows that the study population, as other Iranian populations, has a high level of consanguinity.

  10. Consanguinity and reproductive health among Arabs.

    PubMed

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

    2009-01-01

    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.

  11. Consanguinity and reproductive health among Arabs

    PubMed Central

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

    2009-01-01

    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

  12. Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan.

    PubMed

    Pedurupillay, Christeen Ramane J; Landsend, Erlend Christoffer Sommer; Vigeland, Magnus Dehli; Ansar, Muhammad; Frengen, Eirik; Misceo, Doriana; Strømme, Petter

    2016-01-01

    We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the variants responsible for the two phenotypes. One variant was a homozygous nonsense variant in the inhibitory subunit of the cone-specific cGMP phosphodiesterase gene, PDE6H:c.35C>G (p.Ser12*). PDE6H is expressed in the cones of the retina, which are involved in perception of color vision. This is the second report of a homozygous PDE6H:c.35C>G variant causing incomplete achromatopsia (OMIM 610024), thus strongly supporting the hypothesis that loss-of-function variants in PDE6H cause this visual deficiency phenotype. The second variant was a homozygous missense substitution in the lysophosphatidic acid receptor 6, LPAR6:c.188A>T (p.Asp63Val). LPAR6 acts as a G-protein-coupled receptor involved in hair growth. Biallelic loss-of-function variants in LPAR6 cause hypotrichosis type 8 (OMIM 278150), with or without woolly hair, a form of non-syndromic alopecia. Biallelic LPAR6:c.188A>T was previously described in five families from Pakistan. PMID:27472364

  13. Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan

    PubMed Central

    Pedurupillay, Christeen Ramane J.; Landsend, Erlend Christoffer Sommer; Vigeland, Magnus Dehli; Ansar, Muhammad; Frengen, Eirik; Misceo, Doriana; Strømme, Petter

    2016-01-01

    We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the variants responsible for the two phenotypes. One variant was a homozygous nonsense variant in the inhibitory subunit of the cone-specific cGMP phosphodiesterase gene, PDE6H:c.35C>G (p.Ser12*). PDE6H is expressed in the cones of the retina, which are involved in perception of color vision. This is the second report of a homozygous PDE6H:c.35C>G variant causing incomplete achromatopsia (OMIM 610024), thus strongly supporting the hypothesis that loss-of-function variants in PDE6H cause this visual deficiency phenotype. The second variant was a homozygous missense substitution in the lysophosphatidic acid receptor 6, LPAR6:c.188A>T (p.Asp63Val). LPAR6 acts as a G-protein-coupled receptor involved in hair growth. Biallelic loss-of-function variants in LPAR6 cause hypotrichosis type 8 (OMIM 278150), with or without woolly hair, a form of non-syndromic alopecia. Biallelic LPAR6:c.188A>T was previously described in five families from Pakistan. PMID:27472364

  14. Consanguinity and Birth Defects in the Jerusalem Perinatal Study Cohort

    PubMed Central

    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

    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. PMID:18493143

  15. Modernization and Consanguineous Marriage in Iran.

    ERIC Educational Resources Information Center

    Givens, Benjamin P.; Hirschman, Charles

    1994-01-01

    Used data on 4,667 women from the Iran Fertility Survey to examine trends and social correlates of consanguineous marriage. Found modest increase in proportion of marriages between cousins in Iran from 1940s to 1970s. Results suggest that modernization may be eroding social bases on consanguinity, whereas increased availability of cousins may lead…

  16. Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society.

    PubMed

    Teeuw, Marieke E; Loukili, Ghariba; Bartels, Edien Ac; ten Kate, Leo P; Cornel, Martina C; Henneman, Lidewij

    2014-04-01

    Consanguineous couples should be adequately informed about their increased reproductive risk and possibilities for genetic counselling. Information may only be effective if it meets the needs of the target group. This study aimed to gain more insight into: (1) attitudes of people belonging to ethnic groups in Western society towards consanguinity and their understanding of risk for offspring; and (2) their attitudes regarding reproductive information targeted at consanguineous couples. Dutch Moroccans and Turks were invited to complete an online questionnaire by snowball sampling and by placing a link on two popular Dutch Moroccan/Turkish forum websites between September and October 2011. The questionnaire was completed by 201 individuals who were, on average, neither positive nor negative towards consanguinity. Respondents with a consanguineous partner were more positive, estimated the risk for the offspring lower and were less positive about the provision of risk information to consanguineous couples when compared with respondents without a consanguineous partner. Participants of Turkish origin had a more negative attitude towards consanguinity and estimated the reproductive risk higher than Moroccan participants. More than half of the respondents thought that information should be given before marriage, whereas only 10% thought it should never be provided. The general practitioner was most often mentioned (54%) as the designated professional to inform people. Information about genetic risks related to consanguinity should be offered early, preferably before marriage. The diversity of the target population requires various strategies to disseminate information and reach consanguineous couples with the offer of genetic counselling.

  17. Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society.

    PubMed

    Teeuw, Marieke E; Loukili, Ghariba; Bartels, Edien Ac; ten Kate, Leo P; Cornel, Martina C; Henneman, Lidewij

    2014-04-01

    Consanguineous couples should be adequately informed about their increased reproductive risk and possibilities for genetic counselling. Information may only be effective if it meets the needs of the target group. This study aimed to gain more insight into: (1) attitudes of people belonging to ethnic groups in Western society towards consanguinity and their understanding of risk for offspring; and (2) their attitudes regarding reproductive information targeted at consanguineous couples. Dutch Moroccans and Turks were invited to complete an online questionnaire by snowball sampling and by placing a link on two popular Dutch Moroccan/Turkish forum websites between September and October 2011. The questionnaire was completed by 201 individuals who were, on average, neither positive nor negative towards consanguinity. Respondents with a consanguineous partner were more positive, estimated the risk for the offspring lower and were less positive about the provision of risk information to consanguineous couples when compared with respondents without a consanguineous partner. Participants of Turkish origin had a more negative attitude towards consanguinity and estimated the reproductive risk higher than Moroccan participants. More than half of the respondents thought that information should be given before marriage, whereas only 10% thought it should never be provided. The general practitioner was most often mentioned (54%) as the designated professional to inform people. Information about genetic risks related to consanguinity should be offered early, preferably before marriage. The diversity of the target population requires various strategies to disseminate information and reach consanguineous couples with the offer of genetic counselling. PMID:23921534

  18. KIN AND NON-KIN MARRIAGES AND FAMILY STRUCTURE IN A RICH TRIBAL SOCIETY.

    PubMed

    Bakoush, Omran; Bredan, Amin; Denic, Srdjan

    2016-11-01

    Human consanguinity is often attributed to poverty, lack of education and social insecurity. Nevertheless, kin unions continue to be arranged in socioeconomically transformed societies. This study examined the structure of families and marriages in the rich tribal society of the United Arab Emirates, which has had a high gross domestic product for the last two generations and currently has one of the highest in the world. The respondents were 217 national medical students whose families are proportionally distributed to the population of the country emirates. The rate of parental consanguinity (defined as a union of any two cousins) was 36%. The social status and mean size of consanguineous and non-consanguineous families were not significantly different. In non-consanguineous families, polygamy was more common and the number of half-siblings per family was higher. The extended families were on average 7% larger among non-consanguineous families. In contrast, for the extended families of the participants' grandparents, non-consanguineous families were smaller than their consanguineous counterparts. Participants from consanguineous families indicated that marriage of either a son or daughter was more difficult to arrange than did participants from non-consanguineous families. Though consanguineous parents had their offspring marry consanguineously more often than non-consanguineous parents, the numbers of married offspring in the two groups of families were not different. Consanguineous parents have more difficulty than non-consanguineous parents in finding spouses for themselves and for their offspring, and they arranged kin marriages for their children more often.

  19. Consanguineous marriage and reproduction in Beirut, Lebanon.

    PubMed

    Khlat, M

    1988-08-01

    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.

  20. Large Constituent Families Help Children Parse Compounds

    ERIC Educational Resources Information Center

    Krott, Andrea; Nicoladis, Elena

    2005-01-01

    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…

  1. Familial benign hypercalcaemia. Study of a large family.

    PubMed

    Menko, F H; Bijvoet, O L; Fronen, J L; Sandler, L M; Adami, S; O'Riordan, J L; Schopman, W; Heynen, G

    1983-01-01

    Twenty-seven hypercalcaemic subjects were identified in three generations of a family. There were no clinical complications of chronic hypercalcaemia, but five had had parathyroid surgery which was unsuccessful in four. Twenty of the twenty-seven subjects were compared with twenty-four normocalcaemic controls from the same family and the findings were also compared with those from forty patients with surgically proven primary hyperparathyroidism. The relation between the serum and urinary calcium levels was studied by means of an oral calcium loading test. The ratio of calcium clearance to creatinine clearance was normal in this family (but elevated in the patients with primary hyperparathyroidism) and the concentration of parathyroid hormone was normal, as was the total urinary excretion of cyclic AMP. Thus, there was no evidence of either suppressed or increased parathyroid activity in this familial condition. Basal urinary calcium excretion was normal under steady-state conditions indicating that the hypercalcaemia could not be attributed to either increased bone resorption or increased calcium absorption from the gut. In accordance with this, the serum levels of 1,25-dihydroxycholecalciferol were normal. The hypercalcaemia in this condition can be accounted for in full by an increase in renal tubular reabsorption of calcium, and thus differs from that of primary hyperparathyroidism in which there is increased production of calcium from gut and/or bone as well as an increase in renal tubular reabsorption of calcium. Although the serum phosphate and renal tubular reabsorption of phosphate were both low in patients with familial benign hypercalcaemia, they were not as low as in patients with the same degree of hypercalcaemia due to primary hyperparathyroidism. The changes in phosphate transport in familial benign hypercalcaemia could be explained as a secondary effect of the increased filtered load of calcium in the kidney. The tendency towards hypermagnesaemia in

  2. Consanguinity and disorders of sex development.

    PubMed

    Bashamboo, Anu; McElreavey, Ken

    2014-01-01

    Disorders of sex development (DSD) are defined as 'congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical' [Lee et al., Pediatrics 2006;118:e488-e500]. Studies conducted in Western countries, with low rates of consanguinity, show that truly ambiguous genitalia have an estimated incidence of 1:5,000 births. There are indications that the prevalence of DSD is higher in endogamous communities. The incidence of ambiguous genitalia in Saudi Arabia has been estimated at 1:2,500 live births; whilst in Egypt, it has been estimated at 1:3,000 live births. This may be due in part to an increase in disorders of androgen synthesis associated with 46,XX DSD. There is clearly a need for further studies to address the frequency of DSD in communities with high levels of consanguinity. This will be challenging, as an accurate diagnosis is difficult and expensive even in specialized centres. In developing countries with high levels of consanguinity, these limitations can be compounded by cultural, social and religious factors. Overall there is an indication that consanguinity may lead to an increase in incidences of both 46,XY and 46,XX DSD, and a co-ordinated study of populations with higher incidences of consanguinity/endogamy is needed to resolve this.

  3. Consanguinity studies in Wisconsin I: secular trends in consanguineous marriage, 1843-1981.

    PubMed

    Lebel, R R

    1983-08-01

    Over 920,000 Roman Catholic marriages have taken place since the Archdiocese of Milwaukee was established in 1843. Most of these records are extant, and all have been examined to ascertain consanguineous marriages. The changing average population coefficient of consanguinity has been calculated, by year and by decade, showing a clear downward trend since the turn of the century. The data are compared with reports of consanguineous marriage incidence from around the world, and in particular with all available previous reports from the United States.

  4. Homozygous HOXB1 loss-of-function mutation in a large family with hereditary congenital facial paresis.

    PubMed

    Vogel, Markus; Velleuer, Eunike; Schmidt-Jiménez, Leon F; Mayatepek, Ertan; Borkhardt, Arndt; Alawi, Malik; Kutsche, Kerstin; Kortüm, Fanny

    2016-07-01

    Hereditary congenital facial paresis (HCFP) belongs to the congenital cranial dysinnervation disorders. HCFP is characterized by the isolated dysfunction of the seventh cranial nerve and can be associated with hearing loss, strabismus, and orofacial anomalies. Möbius syndrome shares facial palsy with HCFP, but is additionally characterized by limited abduction of the eye(s). Genetic heterogeneity has been documented for HCFP as one locus mapped to chromosome 3q21-q22 (HCFP1) and a second to 10q21.3-q22.1 (HCFP2). The only known causative gene for HCFP is HOXB1 (17q21; HCFP3), encoding a homeodomain-containing transcription factor of the HOX gene family, which are master regulators of early developmental processes. The previously reported HOXB1 mutations change arginine 207 to another residue in the homeodomain and alter binding capacity of HOXB1 for transcriptional co-regulators and DNA. We performed whole exome sequencing in HCFP-affected individuals of a large consanguineous Moroccan family. The homozygous nonsense variant c.66C>G/p.(Tyr22*) in HOXB1 was identified in the four patients with HCFP and ear malformations, while healthy family members carried the mutation in the heterozygous state. This is the first disease-associated HOXB1 mutation with a likely loss-of-function effect suggesting that all HOXB1 variants reported so far also have severe impact on activity of this transcriptional regulator. © 2016 Wiley Periodicals, Inc. PMID:27144914

  5. Homozygous HOXB1 loss-of-function mutation in a large family with hereditary congenital facial paresis.

    PubMed

    Vogel, Markus; Velleuer, Eunike; Schmidt-Jiménez, Leon F; Mayatepek, Ertan; Borkhardt, Arndt; Alawi, Malik; Kutsche, Kerstin; Kortüm, Fanny

    2016-07-01

    Hereditary congenital facial paresis (HCFP) belongs to the congenital cranial dysinnervation disorders. HCFP is characterized by the isolated dysfunction of the seventh cranial nerve and can be associated with hearing loss, strabismus, and orofacial anomalies. Möbius syndrome shares facial palsy with HCFP, but is additionally characterized by limited abduction of the eye(s). Genetic heterogeneity has been documented for HCFP as one locus mapped to chromosome 3q21-q22 (HCFP1) and a second to 10q21.3-q22.1 (HCFP2). The only known causative gene for HCFP is HOXB1 (17q21; HCFP3), encoding a homeodomain-containing transcription factor of the HOX gene family, which are master regulators of early developmental processes. The previously reported HOXB1 mutations change arginine 207 to another residue in the homeodomain and alter binding capacity of HOXB1 for transcriptional co-regulators and DNA. We performed whole exome sequencing in HCFP-affected individuals of a large consanguineous Moroccan family. The homozygous nonsense variant c.66C>G/p.(Tyr22*) in HOXB1 was identified in the four patients with HCFP and ear malformations, while healthy family members carried the mutation in the heterozygous state. This is the first disease-associated HOXB1 mutation with a likely loss-of-function effect suggesting that all HOXB1 variants reported so far also have severe impact on activity of this transcriptional regulator. © 2016 Wiley Periodicals, Inc.

  6. Social structure and consanguinity in a French mountain Population (1550-1849).

    PubMed

    Rabino-Massa, Emma; Prost, Michel; Boëtsch, Gilles

    2005-04-01

    Sociocultural factors play a crucial role in the variation of consanguinity in a population. The choice of specific matrimonial strategies can favor the closure or opening of the group to the outside, whereas differential fertility affects the gene flow from one generation to another. In the present study we analyzed the role of socioprofessional groups in the maintenance of endogamy and consanguinity in a French Alpine valley: Vallouise in the Briançon area. In mountain environments, where the reproductive space is limited and quickly saturated, the autochthonous families adopt diversified matrimonial strategies. These marriage practices tend to prevent fragmentation of agricultural property. We analyzed the matrimonial behavior in the two main social groups of this population (décideurs and farmers) from 1550 to 1849. To better understand the behavior of the two social groups, we considered the two components of consanguinity, close and distant. Our study showed that the two groups had similar behavior regarding consanguinity. The way to prevent fragmentation of the patrimony was to choose a consanguineous spouse. This type of strategy inevitably leads to a high percentage of endogamy, which in this region of the Alps exceeded 90% through many centuries. PMID:16201137

  7. Consanguinity and its sociodemographic differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan.

    PubMed

    Jabeen, Nazish; Malik, Sajid

    2014-06-01

    Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe. PMID:25076667

  8. THE PREVALENCE OF CONSANGUINEOUS MARRIAGES AND AFFECTING FACTORS IN TURKEY: A NATIONAL SURVEY.

    PubMed

    Kaplan, Sena; Pinar, Gul; Kaplan, Bekir; Aslantekin, Filiz; Karabulut, Erdem; Ayar, Banu; Dilmen, Ugur

    2016-09-01

    This study was carried out by the Turkish Republic Ministry of Health to determine the prevalence of consanguineous marriage and its correlates with socio-demographic and obstetric risk factors in women in Turkey. The cross-sectional, national-level study was carried out from October to December 2013. The study population was composed of women between the ages of 15 and 65 years living in Turkey. The sample size was calculated as 9290 houses within Turkey's 81 provinces so as to improve the Turkish rural-urban expectations by means of systematic stack sampling according to the Turkish Statistical Institute's address-based vital statistics system. The target sample size was 6364, but only eligible 4913 women, who had been married, were included in the study. The consanguineous marriage frequency in the sample was found to be 18.5%, and of these 57.8% were first cousin marriages. Women living in an extended family and whose education level and first marriage ages were low, and whose perceived economic status was poor, had higher frequencies of consanguineous marriage (p<0.001). Consanguineous marriage frequencies were higher (p<0.001) for women who had spontaneous abortions and stillbirths or who had given birth to infants with a congenital abnormality. In this context, it is important to develop national policies and strategies to prevent consanguineous marriages in Turkey.

  9. Consanguinity and its sociodemographic differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan.

    PubMed

    Jabeen, Nazish; Malik, Sajid

    2014-06-01

    Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe.

  10. Attitude of Saudi Arabian adults towards consanguineous marriage

    PubMed Central

    Alharbi, Omar A.; Al-Shaia, Walaa A.; Al-Hamam, Abdulaziz A.; Al-Marzoug, Hala M.; Ahmed, Anwar E.; Bagha, Muhammed

    2015-01-01

    Background: Research on the attitudes of Saudi adults towards consanguinity is scarce. The study aimed to explore the attitudes towards consanguinity and its associations with socio-demographic characteristics in a sample of Saudi adults. Methods: A cross-sectional study was conducted using a self-administered questionnaire. A total of 386 outpatient waiting-area attendees at King Abdul-Aziz Medical City-Riyadh were included. Participants were asked about their socio-demographic characteristics, attitude towards consanguinity and the reasons behind this. Results: The positive attitude towards consanguinity among the study respondents was 48.1% with 95% confidence interval (42.91–53.33%). Social and traditional culture (59.9%) were found to be the predominant reasons for favoring consanguinity in Saudi Arabia. Evidence against a positive attitude towards consanguinity was noted in respondents who received medical information about consanguinity versus those who had not received medical information (42.3% vs. 57%, p-value = 0.008). According to the multivariate logistic model, the odds of a positive attitude towards consanguinity were 2 times higher for males (adjusted odds ratio [aOR]: 2.2; 95% CI: 1.147, 4.290) and 4.1 times higher in respondents in consanguineous marriages (aOR: 4.1; 95% CI: 2.350, 7.156). The odds of a positive attitude towards consanguinity were 50% less in respondents who received health information on consanguinity compared to those who had not received health information about consanguinity (aOR: 0.50; 95% CI: 0.253, 0.863). Conclusion: One in every two Saudi adults favors consanguinity however, Saudi men and women differ in their attitudes towards consanguinity. Receiving health information on consanguinity was associated with a negative attitude towards this practice. PMID:26835408

  11. A study of possible deleterious effects of consanguinity.

    PubMed

    Abdulrazzaq, Y M; Bener, A; al-Gazali, L I; al-Khayat, A I; Micallef, R; Gaber, T

    1997-03-01

    The aim of the study was to determine whether consanguineous marriages result in reproductive wastage and an increased incidence of illness in the offspring in a community with a long history of inbreeding and an expected high rate of consanguineous marriage. A representative sample of 2200 women aged > or = 15 years from Dubai and Al Ain, two cities in the United Arab Emirates, representing on the one hand a modern metropolis and on the other a traditional society, were studied. A questionnaire, which included questions on age, parity, gravidity, number of stillbirths, number of abortions, number of children alive, neonatal deaths and specific illnesses in children, was administered by nurses in antenatal and gynaecological clinics in the two cities. The rate of consanguineous marriage was 50.5% and parity, gravidity, ages and number of children were similar in consanguineous and non-consanguineous groups. There was no significant difference in rates of abortion, stillbirth and neonatal death between the two groups. Overall, there was statistically significant higher reproductive wastage in consanguineous couples, but when the category of less than second cousins was excluded from the consanguineous group no difference was found in reproductive wastage between consanguineous and non-consanguineous marriages. Children born to consanguineous unions also had significantly higher incidences of illnesses (37.1%) than those of non-consanguineous unions (29%). The occurrence of malignancies, congenital abnormalities, mental retardation and physical handicap was significantly higher in offspring of consanguineous than non-consanguineous marriages. In conclusion, consanguinity did not result in reproductive wastage, but was found to be an important factor in the causation of specific illnesses in offspring.

  12. Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis.

    PubMed

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Modell, B

    2016-01-01

    Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information. PMID:26363620

  13. Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis.

    PubMed

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Modell, B

    2016-01-01

    Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information.

  14. Consanguineous marriage in a newly developed country: the Qatari population.

    PubMed

    Bener, Abdulbari; Alali, Khalid A

    2006-03-01

    This study examines the frequency of consanguineous marriage and coefficient of inbreeding in the State of Qatar. The study was conducted in semi-urban areas of Doha between January and May 2004. A sample of 1515 married Qatari females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (54.0%) with a coefficient of inbreeding of 0.02706. The commonest type of consanguineous marriage was between first cousins (34.8%). Double first cousin marriages were common (3.1%) compared with other populations. The consanguinity rate in the State of Qatar has increased from 41.8% to 54.5% in one generation.

  15. Consanguineous marriages : Preconception consultation in primary health care settings.

    PubMed

    Hamamy, Hanan

    2012-07-01

    Consanguinity is a deeply rooted social trend among one-fifth of the world population mostly residing in the Middle East, West Asia and North Africa, as well as among emigrants from these communities now residing in North America, Europe and Australia. The mounting public awareness on prevention of congenital and genetic disorders in offspring is driving an increasing number of couples contemplating marriage and reproduction in highly consanguineous communities to seek counseling on consanguinity. Primary health care providers are faced with consanguineous couples demanding answers to their questions on the anticipated health risks to their offspring. Preconception and premarital counseling on consanguinity should be part of the training of health care providers particularly in highly consanguineous populations.

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

    PubMed

    Al-Arrayed, Shaikha; Hamamy, Hanan

    2012-05-01

    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.

  17. Is consanguineous marriage religiously encouraged? Islamic and Iranian considerations.

    PubMed

    Akrami, Seyed Mohammad; Osati, Zahra

    2007-03-01

    Consanguineous marriage has had considerable attention as a causative factor in the prevalence of genetic disorders. Iran, with its majority Muslim population, has a high rate of consanguineous marriage. In Iranian tradition, first cousin marriage is an acceptable and appreciated custom. However, there seems to be no encouragement of consanguineous marriage in the Islamic context; it is merely mentioned as a traditional and common custom. This paper may help medical professionals providing premarital genetic counselling, who are regularly asked about consanguineous marriage, especially in Islamic communities. Increased public awareness via the mass media would seem to be a priority.

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

    PubMed

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

    2013-10-01

    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.

  19. A large family characterised by nocturnal sudden death

    PubMed Central

    van den Berg, M.P.; Viersma, J.W.; Beaufort-Krol, G.C.M.; Bink-Boelkens, M.Th.E.; Bezzina, C.R.; Veldkamp, M.W.; Brouwer, J.; Haaksma, J.; van Tintelen, J.P.; van Langen, I.M.; Wouda, A.A.; Wilde, A.A.M.

    2002-01-01

    Background We recently identified a novel mutation in large family characterised by premature nocturnal sudden death. In the present paper we provide an overview of the findings in this family. Methods From 1958 onwards, when the first patient presented, we collected clinical data on as many family members as possible. After identification in 1998 of the underlying genetic disorder (SCN5A, 1795insD), genotyping was performed diagnostically. Results Since 1905 unexplained sudden death occurred in 26 family members, 17 of whom died during the night. Besides sudden death, symptomatology was rather limited; only six patients reported syncopal attacks. In one of them, a 13-year-old boy, asystolic episodes up to nine seconds were documented. Until now, the mutation has been found in 114 family members (57 males, 57 females). Carriers of the mutant gene exhibited bradycardia-dependent QT-prolongation, intrinsic sinus node dysfunction, generalised conduction abnormalities, a paucity of ventricular ectopy, and the Brugada sign. Cardiomyopathy or other structural abnormalities were not found in any of the carriers. Electrophysiological studies showed that mutant channels were characterised by markedly reduced INa amplitude, a positive shift of voltage-dependence of activation and a substantial negative shift of voltage-dependence of inactivation of INa. From 1978 onwards, a pacemaker for anti-brady pacing was implanted for prevention of sudden death. In patients in whom a prophylactic pacemaker was implanted no unexplained sudden death occurred, whereas 5 sudden deaths occurred in the group of patients who did not receive a pacemaker. Conclusion We have described a large family with a SCN5A-linked disorder (1795insD) with features of LQT3, Brugada syndrome and familial conduction system disease. Anti-brady pacing was successful in preventing sudden death. The mode of death is possibly bradycardic. ImagesFigure 5 PMID:25696119

  20. Consanguinity and fetal growth in Pakistani Moslems.

    PubMed

    Honeyman, M M; Bahl, L; Marshall, T; Wharton, B A

    1987-03-01

    There is conflicting evidence about the effect of parental consanguinity on fetal growth. Previous studies have not always allowed for other factors that are known to affect birth weight, in particular, gestational age, parity, and maternal height. We have therefore studied this question in the Pakistani Moslem population in Birmingham. Babies born to parents who were first cousins were on average 80 g lighter than those born to unrelated parents, but this difference was not significant for the size of the sample studied. Nor were there any differences in the other measurements of the babies. After expressing birth weight in terms of centiles for gestational age, sex, parity, and maternal height, however, while there was no difference in the overall distribution of centiles, there were more poorly grown babies--that is, weight below the 10th centile--in the first cousin group. We conclude that parental consanguinity is associated with an increase in the number of poorly grown babies but that the overall effect on mean birth weight is small. PMID:3566315

  1. Consanguinity trends and correlates in the Palestinian Territories.

    PubMed

    Assaf, Shireen; Khawaja, Marwan

    2009-01-01

    Secondary analysis of the trends and correlates of consanguinity in the Palestinian Territories was conducted using data from two separate surveys in 1995 and 2004. The analysis was conducted on ever-married women aged 15-54 who were asked about their relation to their husband in both surveys. A total of 16,197 women in 1995 and 4971 women in 2004 were successfully interviewed. Consanguinity was found to be widely practised in the Palestinian Territories with rates of total consanguinity reaching 45% of all marriages in 2004. Analysis was conducted with the data from the two surveys combined and this indicated that consanguinity was significantly decreasing with time after controlling for other variables. Age of the women, their age at marriage, region and locality type they lived in and their standard of living were all found to be significant predictors of consanguinity. The education level of the women was not found to be significant. After controlling for the survey year, women's labour force status was also found to be a non-significant predictor of consanguinity. Although consanguinity was found to be significantly decreasing slowly with time after controlling for other variables, the future trends of consanguinity are not known due to the unstable political situation in the territories, which could have a direct effect on marriage patterns. PMID:18549512

  2. Prevalence of consanguineous marriages and associated factors among Israeli Bedouins.

    PubMed

    Na'amnih, Wasef; Romano-Zelekha, Orly; Kabaha, Ahmed; Rubin, Liza Pollack; Bilenko, Natalya; Jaber, Lutfi; Honovich, Mira; Shohat, Tamy

    2014-10-01

    The Bedouin population in Israel is a semi-nomadic traditional patriarchal society. Consanguineous marriages are very common, contributing to high rates of congenital malformations and genetic diseases, resulting in high infant mortality. Data on consanguineous marriages among Bedouins in Israel are limited. This study examined the current prevalence of consanguineous marriages and their determinants among Israeli Bedouins. One thousand two hundred ninety Bedouin women who delivered in the maternity wards of the only hospital serving the Bedouin population were interviewed between November 2009 and January 2010. The prevalence of consanguineous marriages was 44.8 %. The most common type of spousal relationship was first cousins (65.7 % of all consanguineous marriages). The mean inbreeding coefficient was 0.0238. Factors significantly associated with consanguinity were less years of schooling (OR 0.94, 95 % CI (0.88-0.99), p = 0.02) and younger age at marriage of the wife (OR 0.90, 95 % CI (0.80-0.96), p = 0.0002). In conclusion, the rate of consanguineous marriages among Bedouins is very high, making this population at risk for congenital malformations and genetic diseases. Efforts should be directed at better education and provision of premarital and prenatal counseling on the health consequences of consanguineous marriages and the possibilities to lower those risks.

  3. Parental responses to consanguinity and genetic disease in Saudi Arabia.

    PubMed

    Panter-Brick, C

    1991-01-01

    In-depth interviews of 36 Saudi families whose children suffered from neuro-metabolic disorders were conducted at a specialist hospital in Riyadh in order to examine parental understanding of disease and attitudes towards future births and consanguineous marriages. Parents had difficulty accepting a genetic explanation for diseases that did not affect all children at the time of birth; they also expressed religious or folk beliefs to account for illness. Coping behaviours included denial and resignation to the situation, divorce and remarriage. Some families adopted a cautious approach to cousin marriages and future births; this was significantly related to their education level, but not to previous infant deaths. Awareness of medical facts brought little emotional comfort to parents but allowed for preventive measures through screening adult carriers and identifying affected infants. This study presents new material from Saudi Arabia to strengthen current awareness that the range of religious beliefs, social attitudes and reproductive behaviours adopted by families in a society undergoing rapid change is of direct relevance to health care.

  4. Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors.

    PubMed

    Bennett, Robin L; Motulsky, Arno G; Bittles, Alan; Hudgins, Louanne; Uhrich, Stefanie; Doyle, Debra Lochner; Silvey, Kerry; Scott, C Ronald; Cheng, Edith; McGillivray, Barbara; Steiner, Robert D; Olson, Debra

    2002-04-01

    The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.

  5. Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors.

    PubMed

    Bennett, Robin L; Motulsky, Arno G; Bittles, Alan; Hudgins, Louanne; Uhrich, Stefanie; Doyle, Debra Lochner; Silvey, Kerry; Scott, C Ronald; Cheng, Edith; McGillivray, Barbara; Steiner, Robert D; Olson, Debra

    2002-04-01

    The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations. PMID:26141656

  6. Airfoil family design for large offshore wind turbine blades

    NASA Astrophysics Data System (ADS)

    Méndez, B.; Munduate, X.; San Miguel, U.

    2014-06-01

    Wind turbine blades size has scaled-up during last years due to wind turbine platform increase especially for offshore applications. The EOLIA project 2007-2010 (Spanish Goverment funded project) was focused on the design of large offshore wind turbines for deep waters. The project was managed by ACCIONA Energia and the wind turbine technology was designed by ACCIONA Windpower. The project included the design of a wind turbine airfoil family especially conceived for large offshore wind turbine blades, in the order of 5MW machine. Large offshore wind turbines suffer high extreme loads due to their size, in addition the lack of noise restrictions allow higher tip speeds. Consequently, the airfoils presented in this work are designed for high Reynolds numbers with the main goal of reducing blade loads and mantainig power production. The new airfoil family was designed in collaboration with CENER (Spanish National Renewable Energy Centre). The airfoil family was designed using a evolutionary algorithm based optimization tool with different objectives, both aerodynamic and structural, coupled with an airfoil geometry generation tool. Force coefficients of the designed airfoil were obtained using the panel code XFOIL in which the boundary layer/inviscid flow coupling is ineracted via surface transpiration model. The desing methodology includes a novel technique to define the objective functions based on normalizing the functions using weight parameters created from data of airfoils used as reference. Four airfoils have been designed, here three of them will be presented, with relative thickness of 18%, 21%, 25%, which have been verified with the in-house CFD code, Wind Multi Block WMB, and later validated with wind tunnel experiments. Some of the objectives for the designed airfoils concern the aerodynamic behavior (high efficiency and lift, high tangential coefficient, insensitivity to rough conditions, etc.), others concern the geometry (good for structural design

  7. Prevalence of consanguineous marriages in South Sinai, Egypt.

    PubMed

    Yamamah, G; Abdel-Raouf, E; Talaat, A; Saad-Hussein, A; Hamamy, H; Meguid, N A

    2013-01-01

    A total of 3961 married couples from six major geographical areas representing the South Sinai governorates in Egypt were studied to assess the rate of consanguineous marriage. The population of six selected areas (St Catherines, Nuweiba, Abu Rudeis, Ras Sudr, El Tor and Abu Zenima) were subdivided into Bedouin, urban and mixed populations. A questionnaire-based interview was conducted showing that the consanguinity rate in this region is 37.5%, with the highest rate recorded in Abu Rudeis (52.3%) and lowest rate in Nuweiba (24.1%). Consanguinity was significantly higher among the Bedouin population compared with the urban population in Abu Rudeis, Ras Sudr, El Tor and Abu Zenima, while in St Catherines and Nuweiba there was no statistically significant difference. Among consanguineous couples, 5%, 60% and 35% were double first cousins, first cousins and second cousins respectively. The mean inbreeding coefficient α of the studied population was 0.01845.

  8. Genetics of consanguineous marriage: Impact and importance of counseling.

    PubMed

    Akrami, Seyed Mohammad

    2012-12-01

    Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage.

  9. Genetics of consanguineous marriage: Impact and importance of counseling

    PubMed Central

    Akrami, Seyed Mohammad

    2012-01-01

    Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage.

  10. [Factors influencing the frequency of consanguineous marriages in Japan].

    PubMed

    Imaizumi, Y

    1987-04-01

    A survey of consanguineous marriages in Japan was conducted through questionnaires in 1983. The total number of couples studied was 9225, chosen from 6 widely different areas of Japan. The rates of first cousin marriages and of total consanguineous marriages for all areas were 1.6% and 3.9%, respectively. The rate of total consanguineous marriages was 10 times higher in Fukue-Shi (7.9%) than Asahikawa city area (.78%). The rate of total consanguineous marriages decreased with the marriage year in Japan, where the rate of first cousin marriages has changed remarkably. The rates of consanguineous marriages were estimated according to marital distance between birth places, socioeconomic classes, religion, marriage form, opportunity of encounter, and motivation towards marriage. Among educational groups, the rate was highest in graduates of junior high school for husbands and wives, and the rate was lowest in college or university graduates. Occupationally, the rate was the highest in agriculture, forestry, and fishery for husbands and wives, and the rate was lowest among salesmen for husbands and in professional occupations and researchers for wives. As for opportunities of encounter, the rate was 22-29 times higher in the group for friendship from the time of childhood (25.8%) than in those for school, workplace, and social gatherings (1.2%) and for chance meetings (.9%). A recommendation by parents and relatives was the most frequent reason for consanguineous marriage for both husbands and wives, followed by knowledge of the partner by relatives.

  11. KIC 8462852: Transit of a Large Comet Family

    NASA Astrophysics Data System (ADS)

    Bodman, Eva H. L.; Quillen, Alice

    2016-03-01

    We investigate the plausibility of a cometary source of the unusual transits observed in the KIC 8462852 light curve. A single comet of similar size to those in our solar system produces a transit depth of the order of 10-3 lasting less than a day which is much smaller and shorter than the largest dip observed (˜ 20% for ˜3 days), but a large, closely traveling cluster of comets can fit the observed depths and durations. We find that a series of large comet swarms, with all except one on the same orbit, provides a good fit for the KIC 8462852 data during Quarters 16 and 17, but does not explain the large dip observed during Quarter 8. However, the transit dips only loosely constrain the orbits and can be fit by swarms with periastrons differing by a factor of 10. To reach a transit depth of ˜0.2, the comets need to be in a close group of ˜30, if they are ˜100 km in radius or in a group of ˜300 if they are ˜10 km in radius. The total number of comets required to fit all of the dips is ˜70 ˜ 100 km or ˜700 ˜ 10 km comets. A single comet family from a tidally disrupted Ceres-sized progenitor or the start of a Late Heavy Bombardment period explains the last ˜60 days of the unusual KIC 8462852 light curve.

  12. A large family of filled skutterudites stabilized by electron count.

    PubMed

    Luo, Huixia; Krizan, Jason W; Muechler, Lukas; Haldolaarachchige, Neel; Klimczuk, Tomasz; Xie, Weiwei; Fuccillo, Michael K; Felser, Claudia; Cava, Robert J

    2015-01-01

    The Zintl concept is important in solid-state chemistry to explain how some compounds that combine electropositive and main group elements can be stable at formulas that at their simplest level do not make any sense. The electronegative elements in such compounds form a polyatomic electron-accepting molecule inside the solid, a 'polyanion', that fills its available energy states with electrons from the electropositive elements to obey fundamental electron-counting rules. Here we use this concept to discover a large family of filled skutterudites based on the group 9 transition metals Co, Rh, and Ir, the alkali, alkaline-earth, and rare-earth elements, and Sb4 polyanions. Forty-three new filled skutterudites are reported, with 63 compositional variations--results that can be extended to the synthesis of hundreds of additional new compounds. Many interesting electronic and magnetic properties can be expected in future studies of these new compounds. PMID:25744553

  13. Familial pattern of large vestibular aqueduct syndrome in a Chinese family

    PubMed Central

    Hazmi, Mohd; Ab Aziz, A.; Asma, A.

    2013-01-01

    Large Vestibular Aqueduct Syndrome (LVAS) is the most common radiographic malformation in children with early onset of hearing loss. Usually its occurrence is non-familial, however intriguingly a portion of patients with LVAS is found to have evidence of genetic predisposition. We described cases of LVAS in two siblings of a Chinese family. The elder sister first presented with reduced hearing since childhood and her brother has a similar complaint upon further questioning. Their hearing test showed bilateral sensorineural hearing loss (SNHL) and computed tomography (CT) of temporal bone showed enlarged vestibular aqueduct in both patients. We described an approach to diagnosis of LVAS and highlight the importance of hearing assessment in genetic link hearing loss. PMID:27034633

  14. Consanguineous marriages in Beirut: time trends, spatial distribution.

    PubMed

    Khlat, M

    1988-01-01

    To provide some information on consanguineous marriages, a population based-description of consanguineous marriages in Beirut is presented. A health survey of the city of Beirut, undertaken from July 1, 1983, to August 31, 1984, covered 13,736 individuals, comprising 3033 ever- married women. These women provided information on their marriage and the kinship between the spouses, as well as on the religion, educational and occupational status of their husbands. Armitage's test was used to assess the significance of the time gradient in consanguineous marriages and Bartholomew's test used to assess the significance of the variation in religion, educational level, and occupational status of the residents by level of endogamy in the sector. The overall prevalence of consanguineous marriages was 25%. 56% of marriages occurred between 1st cousins. Splitting the 1st cousin marriages by pedigree showed that patrilateral parallel-cousin marriage was well represented, amounting to 52.2% of all cousin marriages. Over time, consanguineous marriages significantly declined the mean proportion varying from 30% before 1950 to 25% between 1950-69, to about 20% starting form 1970. Cousin marriages remained stable over time, while marriages between distant relatives underwent a significant decline. Rates of consanguineous marriages was computed by sector and mapped. Rates were higher in the western part of the city, comprising a majority of Muslim inhabitants, than in the eastern part, mostly Christian. The higher the proportion of consanguineous marriages, the higher the proportion of husbands of low educational level, of low occupational status, and of Muslim religion.

  15. Effects of polygyny and consanguinity on high fertility in the rural Arab population in South Jordan.

    PubMed

    Sueyoshi, Shuji; Ohtsuka, Ryutaro

    2003-10-01

    Based on the authors' interview survey for 608 randomly selected women of the rural Arab population in the South Ghor district of Jordan, this paper examined the effects of polygyny and consanguinity on high fertility, which was recognized as natural fertility. The prevalence of polygynous and consanguineous marriages was 28.0% and 58.1%, respectively, largely reflecting the population's traditional marriage customs. The findings highlighted a significantly higher total marital fertility rate (TMFR) in the monogamous wives (10.5) than in the senior polygynous (8.1) and junior polygynous wives (8.6); the TMFR did not significantly differ among the wives of non-consanguineous, first-cousin and second-cousin marriages. The formation of polygynous marriage was decided by the husband, mostly as a result of his senior wife's infecundity or sub-fecundity, and the age of the husband at marriage to his junior polygynous wife was high in many cases, leading to a decline in this wife's fecundity.

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

    PubMed Central

    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

    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. PMID:21885617

  17. The impact of consanguinity on neonatal and infant health.

    PubMed

    Bittles, A H; Black, M L

    2010-11-01

    Marriage between biological relatives is widely popular in many parts of the world, with over 1000 million people living in countries where 20-50+% of unions are contracted between couples related as second cousins or closer. Consanguinity is, however, a controversial topic, in part due to public misunderstanding, complicated by often exaggerated past estimates of the adverse health outcomes. While some consanguineous couples are at high risk of conceiving a child with a genetic disorder, they are a small minority. Thus a multi-population meta-analysis has indicated an excess infant death rate of 1.1% in the progeny of first cousins, and even this figure may be compromised by inadequate control for non-genetic variables. The benefits as well as the disadvantages of consanguineous marriage are assessed and discussed, with specific consideration given to the health of migrant communities in Western countries, among whom first cousin marriage remains preferential.

  18. Consanguinity Mapping of Congenital Heart Disease in a South Indian Population

    PubMed Central

    McGregor, Tracy L.; Misri, Amit; Bartlett, Jackie; Orabona, Guilherme; Friedman, Richard D.; Sexton, David; Maheshwari, Sunita; Morgan, Thomas M.

    2010-01-01

    Background Parental consanguinity is a risk factor for congenital heart disease (CHD) worldwide, suggesting that a recessive inheritance model may contribute substantially to CHD. In Bangalore, India, uncle-niece and first cousin marriages are common, presenting the opportunity for an international study involving consanguinity mapping of structural CHD. We sought to explore the recessive model of CHD by conducting a genome-wide linkage analysis utilizing high-density oligonucleotide microarrays and enrolling 83 CHD probands born to unaffected consanguineous parents. Methodology/Principal Findings In this linkage scan involving single nucleotide polymorphism (SNP) markers, the threshold for genome-wide statistical significance was set at the standard log-of-odds (LOD) score threshold of 3.3, corresponding to 1995∶1 odds in favor of linkage. We identified a maximal single-point LOD score of 3.76 (5754∶1 odds) implicating linkage of CHD with the major allele (G) of rs1055061 on chromosome 14 in the HOMEZ gene, a ubiquitously expressed transcription factor containing leucine zipper as well as zinc finger motifs. Re-sequencing of HOMEZ exons did not reveal causative mutations in Indian probands. In addition, genotyping of the linked allele (G) in 325 U.S. CHD cases revealed neither genotypic nor allele frequency differences in varied CHD cases compared to 605 non-CHD controls. Conclusions/Significance Despite the statistical power of the consanguinity mapping approach, no single gene of major effect could be convincingly identified in a clinically heterogeneous sample of Indian CHD cases born to consanguineous parents. However, we are unable to exclude the possibility that noncoding regions of HOMEZ may harbor recessive mutations leading to CHD in the Indian population. Further research involving large multinational cohorts of patients with specific subtypes of CHD is needed to attempt replication of the observed linkage peak on chromosome 14. In addition, we

  19. Genetics of consanguineous marriage: Impact and importance of counseling.

    PubMed

    Akrami, Seyed Mohammad

    2012-12-01

    Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage. PMID:27625826

  20. Mismatches in genetic markers in a large family study.

    PubMed Central

    Ashton, G C

    1980-01-01

    The Hawaii Family Study of Cognition provided an opportunity to investigate the frequency and implications of non-agreement, or mismatches, between observed and expected genetic marker phenotypes of husbands, wives, and children. Mismatch data from 68 families in which one or both spouses were known not to be a biological parent were used to determine the rate of undeclared nonparentage in 1,748 families in which conventional relationships were claimed. Two independent approaches gave consistent estimates, suggesting that approximately 2.3% of the 2,839 tested children from these families were probably the result of infidelity, concealed adoption, or another event. About two-thirds of the mismatches detected were probably due to properties of the techniques employed. PMID:6930820

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

    PubMed Central

    Carre, I; Johnston, B; Thomas, P; Morrison, P

    1999-01-01

    BACKGROUND—Familial hiatal hernia has only rarely been documented.
AIMS—To describe the pattern of inheritance of familial hiatal hernia within an affected family.
SUBJECTS—Thirty eight members of a family pedigree across five generations.
METHODS—All family members were interviewed and investigated by barium meal for evidence of a hiatal hernia.
RESULTS—Twenty three of 38 family members had radiological evidence of a hiatal hernia. No individual with a hiatal hernia was born to unaffected parents. In one case direct male to male transmission was shown.
CONCLUSIONS—Familial inheritance of hiatal hernia does occur. Evidence of direct male to male transmission points to an autosomal dominant mode of inheritance.


Keywords: familial hiatal hernia; Barrett's oesophagus; autosomal dominant genetics PMID:10517898

  2. Consanguinity and genetic diseases in North Africa and immigrants to Europe.

    PubMed

    Anwar, Wagida A; Khyatti, Meriem; Hemminki, Kari

    2014-08-01

    Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of marriage between close relatives originating from a common ancestor. With limited natural selection, recessive genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29-33% in Morocco. As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are common in NA, but with immigration they have spread to Europe and to other parts of the world. Another example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country, and there is no evidence that any native Swede would have been diagnosed with this disease. The examples discussed in this chapter show that the historic movement of populations and current immigration are influencing the concept of 'endemic' disease. PMID:25107999

  3. Consanguinity and early mortality in the Muslim populations of India and Pakistan.

    PubMed

    Hussain, R; Bittles, A H; Sullivan, S

    2001-01-01

    Empirical information from studies conducted in Pakistan has indicated a high level of offspring mortality that can be attributed to parental consanguinity even when non-biological variables are controlled. However, with the exception of some small and geographically restricted studies, few comparable data are available on the influence of inbreeding in child survival among the Muslim population of India, which numbers between 100 and 120 million. The present study compares deaths during the first 5 years of life among the offspring of first cousin (F = 0.0625) and non-consanguineous unions (F = 0), using data collected in the 1992-1993 Indian National Family Health Survey (NFHS) and the 1990-1991 Pakistan Demographic and Health Survey (PDHS). The focus was on determinants of mortality in live-born children to age 5 years. In both countries, bivariate analyses indicated that mortality was significantly increased in the offspring of first cousin unions during the neonatal and post-neonatal, total infant, and under-5 year periods. The findings were confirmed by multivariate regression, which incorporated control for a range of biological and demographic factors.

  4. Consanguinity and genetic diseases in North Africa and immigrants to Europe.

    PubMed

    Anwar, Wagida A; Khyatti, Meriem; Hemminki, Kari

    2014-08-01

    Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of marriage between close relatives originating from a common ancestor. With limited natural selection, recessive genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29-33% in Morocco. As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are common in NA, but with immigration they have spread to Europe and to other parts of the world. Another example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country, and there is no evidence that any native Swede would have been diagnosed with this disease. The examples discussed in this chapter show that the historic movement of populations and current immigration are influencing the concept of 'endemic' disease.

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

    PubMed

    Martin, S N; Sutherland, J; Levin, A V; Klose, R; Priston, M; Héon, E

    2000-06-01

    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 community in south western Ontario was affected with congenital glaucoma and was studied by linkage and mutational analysis to identify the glaucoma related genetic defects. Linkage analysis using the MLINK component of the LINKAGE package (v 5.1) showed evidence of linkage to the 2p21 region (Zmax=3.34, theta=0, D2S1348 and D2S1346). Mutational analysis of the primary candidate gene, CYP1B1, was done by direct cycle sequencing, dideoxy fingerprinting analysis, and fragment analysis. Two different disease causing mutations in exon 3, 1410del13 and 1505G-->A, both segregated with the disease phenotype. The two different combinations of these alleles appeared to result in a variable expressivity of the phenotype. The compound heterozygote appeared to have a milder phenotype when compared to the homozygotes for the 13 bp deletion. The congenital glaucoma phenotype for this large inbred Amish family is the result of mutations in CYP1B1 (2p21). The molecular information derived from this study will be used to help identify carriers of the CYP1B1 mutation in this community and optimise the management of those at risk of developing glaucoma. PMID:10851252

  6. CONSANGUINITY AND INBREEDING COEFFICIENT IN TRIBAL PASHTUNS INHABITING THE TURBULENT AND WAR-AFFECTED TERRITORY OF BAJAUR AGENCY, NORTH-WEST PAKISTAN.

    PubMed

    Ahmad, Bashir; Rehman, Atta Ur; Malik, Sajid

    2016-01-01

    The north-western populations of Pakistan in the Federally Administered Tribal Areas (FATA) adjoining the Pakistan-Afghanistan border are an amalgamation of native and migrated Pashtun tribes. These tribal populations are in transition due to war conditions and geo-political turmoil on both sides of the border since the Soviet invasion in 1979. Bio-demographic and epidemiological data for these tribes are scarce. A prospective cross-sectional sample of 967 males was selected from a representative Pashtun population of Bajaur Agency, and information obtained on bio-demographic variables and marital union types. Analysis of these data revealed that consanguinity was 22.34% and the inbreeding coefficient F was calculated to be 0.0134. The inbreeding coefficient was observed to be higher in subjects who were illiterate, had unskilled jobs and who belonged to younger age categories, extended families and the Tarkalani tribe. Further analyses with respect to temporal variables like subject's age, year of marriage and age at marriage revealed that after a transition in marital union types in the early 80s, there has been a declining trend in the rate of consanguineous unions. Further, consanguineous unions in the parental generation were only 5%, but parental marriage types were predictors of subjects' marital union types. The data further establish that, contrary to a general notion about a high consanguinity rate in Pakistan, consanguineous unions are not common in Bajaur Agency and first cousin marriage is not the preferred type. Furthermore, this research shows that there is a great regional variation in the pattern of consanguinity in Pakistan that needs to be documented in order to draw a more comprehensive picture of the inbreeding coefficient in the country.

  7. The frequency of consanguineous marriage among British Pakistanis.

    PubMed

    Darr, A; Modell, B

    1988-03-01

    An enquiry answered by 100 randomly selected British Pakistani mothers in the postnatal wards of two hospitals in West Yorkshire showed that 55 were married to their first cousins, while in only 33 cases had their mother been married to her first cousin. This suggests an increasing rate of consanguineous marriage in this relatively small group, by contrast with the decreasing rate observed in some other countries. The genetic implications merit further study. PMID:3351906

  8. Reflections on the consanguinity and birth outcome debate.

    PubMed

    Ahmad, W I

    1994-12-01

    The high rate of consanguineous marriages has been implicated as an important factor in the high rates of perinatal mortality and congenital malformations among the UK Pakistani population. This paper critically considers the debate on consanguinity and birth outcome. A critical review of epidemiological literature is placed in the context of wider, but centrally important, debates on social class and ethnic categorizations, notions of culture and literature on racism. The epidemiological literature is inconsistent in its findings, and is often based on data and arguments of dubious validity. Equally, notions of social class, ethnicity and culture used in such studies lack sophistication and require reconsideration. Health policy options based on promoting cultural change in marriage patterns, conveniently but unjustifiably, shift the blame of poor birth outcome onto the Pakistani community and are doomed to failure. The consanguinity hypothesis is over-simplistic to explain the higher rates of perinatal mortality and congenital malformations among the Pakistani population. Its popularity rests less on its scientific merit and more on its convenience in shifting the blame onto supposedly deviant cultures and marriage patterns and its fit with racist ideas of alienness and deviance. PMID:7880573

  9. Reflections on the consanguinity and birth outcome debate.

    PubMed

    Ahmad, W I

    1994-12-01

    The high rate of consanguineous marriages has been implicated as an important factor in the high rates of perinatal mortality and congenital malformations among the UK Pakistani population. This paper critically considers the debate on consanguinity and birth outcome. A critical review of epidemiological literature is placed in the context of wider, but centrally important, debates on social class and ethnic categorizations, notions of culture and literature on racism. The epidemiological literature is inconsistent in its findings, and is often based on data and arguments of dubious validity. Equally, notions of social class, ethnicity and culture used in such studies lack sophistication and require reconsideration. Health policy options based on promoting cultural change in marriage patterns, conveniently but unjustifiably, shift the blame of poor birth outcome onto the Pakistani community and are doomed to failure. The consanguinity hypothesis is over-simplistic to explain the higher rates of perinatal mortality and congenital malformations among the Pakistani population. Its popularity rests less on its scientific merit and more on its convenience in shifting the blame onto supposedly deviant cultures and marriage patterns and its fit with racist ideas of alienness and deviance.

  10. Broad scan linkage analysis in a large Tourette family pedigree

    SciTech Connect

    Peiffer, A.; Leppert, M.; Wetering, B.J.M. van der

    1994-09-01

    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.

  11. FamAgg: an R package to evaluate familial aggregation of traits in large pedigrees

    PubMed Central

    Rainer, Johannes; Taliun, Daniel; D’Elia, Yuri; Pattaro, Cristian; Domingues, Francisco S.; Weichenberger, Christian X.

    2016-01-01

    Summary: Familial aggregation analysis is the first fundamental step to perform when assessing the extent of genetic background of a disease. However, there is a lack of software to analyze the familial clustering of complex phenotypes in very large pedigrees. Such pedigrees can be utilized to calculate measures that express trait aggregation on both the family and individual level, providing valuable directions in choosing families for detailed follow-up studies. We developed FamAgg, an open source R package that contains both established and novel methods to investigate familial aggregation of traits in large pedigrees. We demonstrate its use and interpretation by analyzing a publicly available cancer dataset with more than 20 000 participants distributed across approximately 400 families. Availability and implementation: The FamAgg package is freely available at the Bioconductor repository, http://www.bioconductor.org/packages/FamAgg. Contact: Christian.Weichenberger@eurac.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26803158

  12. Demographic characteristics of the Israeli Arab community in connection with consanguinity.

    PubMed

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

    1996-12-01

    In a previous nationwide survey of the Israeli Arab community we showed that 44% of all marriages are consanguineous. Further analysis of the data from this previous survey was undertaken, and we defined six demographic characteristics that may be associated with consanguinity or non-consanguinity in the marriages. Of these, we found a significant correlation (P <0.001) with religion (for Moslems, odds ratio 1.7), consanguinity in parents' marriages, and the respondent's attitude towards consanguineous marriage. The educational level achieved was not a major factor in the type of marriage chosen. These findings should enable us to plan specifically designed educational and counseling programs with a view to reducing the overall incidence of consanguineous marriage.

  13. The practice of consanguineous marriage in Oman: prevalence, trends and determinants.

    PubMed

    Islam, M Mazharul

    2012-09-01

    The practice of consanguineous marriage has been the culturally preferred form of marriage in most Arab and the Middle Eastern countries, including Oman, but due to a paucity of population-based data in the past there is a dearth of information about its form and dynamics in Oman. Recent national-level surveys allow this gap to be filled. This paper examines the prevalence, trends and determinants of consanguineous marriages in Oman using data from the 2000 Oman National Health Survey. The results indicate a very high prevalence of consanguineous marriage in Oman, as more than half (52%) of marriages are consanguineous. First cousin unions are the most common type of consanguineous unions, constituting 39% of all marriages and 75% of all consanguineous marriages. The study observed various patterns of consanguinity, some of them common with other Arab nations, and some unique in nature. Women's age at marriage, employment, place of childhood residence and geographical region appear to be significant determinants of consanguineous marriages. Consanguineous marriage shows a strong association with marital stability, early age at marriage and early-age childbearing. There has been no appreciable change in the prevalence of consanguineous unions in Oman over the last four decades despite massive socioeconomic development and modernization. However, recent marriage cohorts show slight declining trends. The results suggest that consanguinity is likely to remain stable in the future or decline at a slow rate. Specific health education and genetic counselling should be followed in line with WHO recommendations to minimize the negative health consequences of consanguinity for child health.

  14. A large family of anti‐activators accompanying XylS/AraC family regulatory proteins

    PubMed Central

    Yan, Michael B.; Tran, Minh; Wright, Nathan; Luzader, Deborah H.; Kendall, Melissa M.; Ruiz‐Perez, Fernando; Nataro, James P.

    2016-01-01

    Summary AraC Negative Regulators (ANR) suppress virulence genes by directly down‐regulating AraC/XylS members in Gram‐negative bacteria. In this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for ANRs among different bacterial pathogens. We identified more than 200 ANRs distributed in diverse clinically important gram negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR‐activated regulator), a prototype member of the ANR family in EAEC, binds with high affinity to the central linker domain of AraC‐like member AggR. ANR‐AggR binding disrupted AggR dimerization and prevented AggR‐DNA binding. ANR homologs of Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable of complementing Aar activity by repressing aggR expression in EAEC strain 042. ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other members of the AraC family, including Rns and ToxT. The predicted proteins of all ANR members exhibit three highly conserved predicted α‐helices. Site‐directed mutagenesis studies suggest that at least predicted α‐helices 2 and 3 are required for Aar activity. In sum, our data strongly suggest that members of the novel ANR family act by directly binding to their cognate AraC partners. PMID:27038276

  15. Malaysia: where big is still better. For Malays, large families are part of the plan.

    PubMed

    1993-11-01

    The benefits of various-sized families in Malaysia were discussed by several women and supplemented with official statements on family planning (FP). The Director of the National Population and Family Development, Dr. Raj Karim, advised that maternal health is jeopardized when women have more than five children. About 30% of reproductive age women in Malaysia have five or more children. A Federation of FP Associations spokesperson agreed that women should be advised of the dangers of bearing over five children, of the importance of spacing births two to four years apart, and of the ideal age of childbearing (21-39 years). The government lacks an official policy on family size. The government position is, however, compatible with Islamic teachings on spacing in order to protect the health of the mother and child. Islamic law does not permit sterilization or abortion. The "fatwas" of Islamic teaching may have been misconstrued by those not using any form of contraception. Dr. Karim, who has five children, reported that having a large family can be difficult for a woman with a job, a career, and a husband or when both parents work. Most Malays desire large families. The average Malay family size was 4.1 children in 1990; Malaysian Chinese have fertility of 2.3 children and Malaysian Indians have 2.6 children. People say that the benefits outweigh the hardships of a large family.

  16. Influence of parental consanguineous marriages on age at onset of bipolar disorder.

    PubMed

    Saadat, Mostafa

    2012-07-30

    The present study was performed to investigate the association between parental consanguineous marriages and age at onset of bipolar disorder (BPD). A total of 195 BPD patients participated in the study. Kaplan-Meier analysis revealed that relationships between age at onset and cumulative proportion of patients have different patterns with respect to types of parental marriages. Among early onset cases, the age at onset was higher for offspring of consanguineous than unrelated marriages, whereas in late onset cases the age at onset was lower for offspring of consanguineous than unrelated marriages. However, there was no difference between consanguineous and unrelated marriages for intermediate age at onset.

  17. Models of population-based analyses for data collected from large extended families

    PubMed Central

    Lee, Elisa T.; Howard, Barbara V.; Fabsitz, Richard R.; Devereux, Richard B.; MacCluer, Jean W.; Laston, Sandra; Comuzzie, Anthony G.; Shara, Nawar M.; Welty, Thomas K.

    2014-01-01

    Large studies of extended families usually collect valuable phenotypic data that may have scientific value for purposes other than testing genetic hypotheses if the families were not selected in a biased manner. These purposes include assessing population-based associations of diseases with risk factors/covariates and estimating population characteristics such as disease prevalence and incidence. Relatedness among participants however, violates the traditional assumption of independent observations in these classic analyses. The commonly used adjustment method for relatedness in population-based analyses is to use marginal models, in which clusters (families) are assumed to be independent (unrelated) with a simple and identical covariance (family) structure such as those called independent, exchangeable and unstructured covariance structures. However, using these simple covariance structures may not be optimally appropriate for outcomes collected from large extended families, and may under- or over-estimate the variances of estimators and thus lead to uncertainty in inferences. Moreover, the assumption that families are unrelated with an identical family structure in a marginal model may not be satisfied for family studies with large extended families. The aim of this paper is to propose models incorporating marginal models approaches with a covariance structure for assessing population-based associations of diseases with their risk factors/covariates and estimating population characteristics for epidemiological studies while adjusting for the complicated relatedness among outcomes (continuous/categorical, normally/non-normally distributed) collected from large extended families. We also discuss theoretical issues of the proposed models and show that the proposed models and covariance structure are appropriate for and capable of achieving the aim. PMID:20882324

  18. Internal organization of large protein families: relationship between the sequence, structure and function based clustering

    PubMed Central

    Cai, Xiao-hui; Jaroszewski, Lukasz; Wooley, John; Godzik, Adam

    2011-01-01

    The protein universe can be organized in families that group proteins sharing common ancestry. Such families display variable levels of structural and functional divergence, from homogenous families, where all members have the same function and very similar structure, to very divergent families, where large variations in function and structure are observed. For practical purposes of structure and function prediction, it would be beneficial to identify sub-groups of proteins with highly similar structures (iso-structural) and/or functions (iso-functional) within divergent protein families. We compared three algorithms in their ability to cluster large protein families and discuss whether any of these methods could reliably identify such iso-structural or iso-functional groups. We show that clustering using profile-sequence and profile-profile comparison methods closely reproduces clusters based on similarities between 3D structures or clusters of proteins with similar biological functions. In contrast, the still commonly used sequence-based methods with fixed thresholds result in vast overestimates of structural and functional diversity in protein families. As a result, these methods also overestimate the number of protein structures that have to be determined to fully characterize structural space of such families. The fact that one can build reliable models based on apparently distantly related templates is crucial for extracting maximal amount of information from new sequencing projects. PMID:21671455

  19. Absence of cystic fibrosis mutations in a large Asian population sample and occurrence of a homozygous S549N mutation in an inbred Pakistani family.

    PubMed Central

    Curtis, A; Richardson, R J; Boohene, J; Jackson, A; Nelson, R; Bhattacharya, S S

    1993-01-01

    The occurrence of cystic fibrosis is very rare in the Asian population. Carriers of the mutations most commonly found in Caucasians were not detected in a large Asian population sample of almost 900 chromosomes. However, an affected Pakistani child born to consanguineous parents was further investigated and shown to be homozygous for the mutation S549N (G-->A). Molecular and clinical data are presented which may improve our understanding of the phenotypic effects of the S549N mutation in the CFTR gene. Images PMID:7680378

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

    PubMed Central

    Zhu, Ye; Gu, Xiang; Xu, Chao

    2016-01-01

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

  1. Consanguineous marriages in the population of Sheikhupura (Punjab), Pakistan.

    PubMed

    Shami, S A; Iqbal, I

    1983-01-01

    This study was based on 1007 couples from the Sheikhupura population. The proportions of various parental relationships were: 0.3784 1st cousins, 0.0318 1st cousins once removed, 0.0784 double 2nd cousins, 0.1033 bradari distant relations, 0.3416 bradari, and 0.0665 unrelated parents. Mean paternal ages in unrelated couples are significantly higher than in 1st cousins, double 2nd cousins, and bradari relations. The differences in paternal and maternal ages are significantly higher in unrelated relations as compared to 1st cousins and double 2nd cousins. Procounced effects of consanguinity on parental deaths and neonatal deaths were observed in 1st cousin marriages compared to other relationships. Juvenile and infant deaths show comparatively less effects of consanguinity in 1st cousin marriages. Mean coefficient of inbreeding calculated for this population was 0.0271. Lethal gene equivalents calculated were 1.5424. The added risk of affected children in 1st cousins over that of unrelated parents was 4.82%. The results suggest that the deleterious genes show their effects more in the prenatal than in the postnatal period.

  2. Structure and evolutionary history of a large family of NLR proteins in the zebrafish

    PubMed Central

    Zielinski, Julia; Kondrashov, Fyodor

    2016-01-01

    Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins. Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families. We describe a family of nearly 400 NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system. PMID:27248802

  3. An epidemiological study on consanguineous marriage among urban population in Alexandria.

    PubMed

    Mohamed, M S

    1995-01-01

    The study was carried out using a cross-sectional approach, involving interviews with 500 households randomly selected from three urban areas in Alexandria (Bab Sharki, El Gomrok and Karmouz). A questionnaire interview was conducted with married females in these households to determine prevalence of consanguineous marriages and to study knowledge of married females about causes and effects of consanguineous marriages. Prevalence of consanguineous marriages among 500 married females was 22.8% with the highest frequency among marriage between first cousins (15.8%). Average inbreeding coefficient up to the marriage between second cousins equals to 0.01172. The linear trend of consanguineous marriages throughout the last 50 years was statistically significant. Age at marriage was younger in consanguineous marriages than non consanguineous marriages. Longstanding familiarity and sharing same traditions and customs with male relatives were the main causes of consanguineous marriages. The majority of the studied females (42.2%) reported that consanguineous marriage is harmful while 29.6% reported that it has no effect on offsprings.

  4. Evidence for ASD recurrence rates and reproductive stoppage from large UK ASD research family databases.

    PubMed

    Wood, Claire L; Warnell, Frances; Johnson, Mary; Hames, Annette; Pearce, Mark S; McConachie, Helen; Parr, Jeremy R

    2015-02-01

    Following a diagnosis of a developmental disorder such as autism spectrum disorder (ASD) in early childhood, parents may decide to have fewer children than previously planned. The tendency for families to halt reproduction after receiving a diagnosis for one child is known as reproductive stoppage. Stoppage may lead to an underestimate of recurrence risk estimates of parents having more than one child with ASD. Using two large UK ASD family databases, we investigated recurrence rates for ASD and evidence for reproductive stoppage for both ASD and undiagnosed ASD/broader autism phenotype in a subgroup of families. Reproductive stoppage was tested for using the Mann-Whitney U-test to disprove the null hypothesis that affected and nonaffected children were distributed randomly by birth order. Dahlberg's later-sib method was used to estimate recurrence risk and take stoppage into account. Data were available from 299 families (660 children) including 327 with ASD. Ten percent of the complete families had more than one child with an ASD. Using Dahlberg's later-sib method, the recurrence risk for ASD was 24.7% overall and 50.0% in families with two or more older siblings with ASD. Children with ASD were born significantly later in families than those without ASD in all sibship combinations. This study shows strong evidence that ASD is associated with reproductive stoppage. These data have important implications for family planning and genetic counseling.

  5. Ultra Large Gene Families: A Matter of Adaptation or Genomic Parasites?

    PubMed Central

    Schiffer, Philipp H.; Gravemeyer, Jan; Rauscher, Martina; Wiehe, Thomas

    2016-01-01

    Gene duplication is an important mechanism of molecular evolution. It offers a fast track to modification, diversification, redundancy or rescue of gene function. However, duplication may also be neutral or (slightly) deleterious, and often ends in pseudo-geneisation. Here, we investigate the phylogenetic distribution of ultra large gene families on long and short evolutionary time scales. In particular, we focus on a family of NACHT-domain and leucine-rich-repeat-containing (NLR)-genes, which we previously found in large numbers to occupy one chromosome arm of the zebrafish genome. We were interested to see whether such a tight clustering is characteristic for ultra large gene families. Our data reconfirm that most gene family inflations are lineage-specific, but we can only identify very few gene clusters. Based on our observations we hypothesise that, beyond a certain size threshold, ultra large gene families continue to proliferate in a mechanism we term “run-away evolution”. This process might ultimately lead to the failure of genomic integrity and drive species to extinction. PMID:27509525

  6. The prevalence and correlates of consanguineous marriages in Yemen: similarities and contrasts with other Arab countries.

    PubMed

    Jurdi, Rozzet; Saxena, Prem C

    2003-01-01

    Using data on 9762 women from the 1997 Yemen Demographic and Maternal and Child Health Survey, this paper examines the prevalence and socioeconomic correlates of consanguineous marriages in Yemen. The results indicate that 40% of marriages are consanguineous, over 85% of which are between first cousins. The prevalence of consanguineous marriages appears to have increased over time, particularly for the last marriage cohort. As for socioeconomic correlates, the study confirms the inverse association between consanguineous marriages and women's education and occupation, age at marriage and economic status. However, no statistically significant difference in the prevalence of consanguinity has been found by place of residence and geographical region. Somewhat unexpected results have been obtained by husband's background characteristics, with higher educated men and those working in the modern sector of the economy being more likely to be married to cousins.

  7. An ABCD1 Mutation (c.253dupC) Caused Diverse Phenotypes of Adrenoleukodystrophy in an Iranian Consanguineous Pedigree

    PubMed Central

    Mehrpour, Masoud; Gohari, Faeze; Dizaji, Majid Zaki; Ahani, Ali; Malicdan, May Christine V.; Behnam, Babak

    2016-01-01

    Objectives Current study was the first to report a consanguineous Iranian pedigree with ABCD1 mutation. Methods Targeted molecular analysis was initially performed in three affected individuals in one family suspected to have X-ALD due to chronic progressive spasticity. Upon confirmation of genetic diagnosis, further neurologic and genetic evaluation of all family members was done. Results A mutation in ABCD1 was identified in 35 affected individuals (out 96 pedigree members). The c. 253dup, in exon 1, leads to a frame shift and a premature stop codon at amino acid position 194 (p.Arg85Profs*110). Surprisingly, affected individuals in our cohort show some variability in phenotype, including childhood cerebral ALD, adrenomyeloneuropathy, and addison-only disease phenotypes, expanding the phenotype of X-ALD with p.Arg85Profs*110. Conclusion This report characterizes the clinical spectrum of an expanded Iranian pedigree with X-ALD due to an ABCD1 mutation. Given a high frequency of carriers in this region, we expect the prevalence of X-ALD to be higher, underscoring the importance of genetic counseling through reliable identification of heterozygous as well as homozygote females in consanguineous communities. PMID:27489563

  8. Oculocutaneous albinism and consanguineous marriage among Spanish Gitanos or Calé--a study of 83 cases.

    PubMed

    Gamella, Juan F; Carrasco-Muñoz, Elisa Martín; Núñez Negrillo, Ana María

    2013-09-01

    This paper studies 83 cases of oculocutaneous albinism (OCA) in family networks of Gitanos in southeastern Spain, and analyzes their sustained inbreeding patterns and complex genealogical relationships. It is based in the family and genealogy reconstitution of the Gitano population of 22 contiguous localities using ethnographic and historical demography methods. The study found a prevalence of OCA among Gitanos in the area of about 1: 1,200. Most of the cases belong to three extended kin networks in which consanguineous marriages have been common for generations. In these networks there are other cases of visual and auditive congenital anomalies, and other birth defects such as brachydactily, polydactily, neurological defects, Potter Sequence, etc. In 61 OCA cases it was possible to trace inbreeding links with a depth of three to nine generations. For these cases the estimated alpha (average of the inbreeding coefficient, F) is 0.0222. Relationships between the parents of people affected are of three types: close, as between first or second cousins; distant, as between third or fourth cousins, and non-existent, as in mixed marriages. In most cases, however, persons with albinism are linked by multiple consanguineous links. Albinism seems to be a visible example of a high prevalence of birth defects in this minority, associated with founder effects, sustained inbreeding and high fertility rates. These conditions derive from Gitano's marriage preferences and pronatalist strategies. In turn, these strategies have to be related to the exclusion, persecution and segregation that Spanish Gypsies have suffered for centuries.

  9. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation.

    PubMed

    Molven, Anders; Grimstvedt, Magne B; Steine, Solrun J; Harland, Mark; Avril, Marie-Françoise; Hayward, Nicholas K; Akslen, Lars A

    2005-09-01

    Mutations in two loci encoding cell-cycle-regulatory proteins have been shown to cause familial malignant melanoma. About 20% of melanoma-prone families bear a mutation in the CDKN2A locus, which encodes two unrelated proteins, p16INK4A and p14ARF. Mutations in the other locus, CDK4, are much rarer and have been linked to the disease in only three families worldwide. In the 1960s, a large Norwegian pedigree with multiple atypical nevi and malignant melanomas was identified. Subsequently, six generations and more than 100 family members were traced and 20 cases of melanoma verified. In this article, we report that CDK4 codon 24 is mutated from CGT to CAT (Arg24His) in this unusually large melanoma kindred. Intriguingly, one of the family members had ocular melanoma, but the CDK4 mutation could not be detected in archival tissue samples from this subject. Thus, the case of ocular melanoma in this family was sporadic, suggesting an etiology different from that of the skin tumors. The CDK4 mutation in the Norwegian family was identical to that in melanoma families in France, Australia, and England. Haplotype analysis using microsatellite markers flanking the CDK4 gene and single-nucleotide polymorphisms within the gene did not support the possibility that there was a common founder, but rather indicated at least two independent mutational events. All CDK4 melanoma families known to date have a substitution of amino acid 24. In addition to resulting from selection pressure, this observation may be explained by the CG dinucleotide of codon 24 representing a mutational hot spot in the CDK4 gene.

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

    PubMed

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

    2014-04-01

    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 6 year 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

  11. SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia

    PubMed Central

    Nickerson, Sarah L.; Marquis-Nicholson, Renate; Claxton, Karen; Ashton, Fern; Leong, Ivone U. S.; Prosser, Debra O.; Love, Jennifer M.; George, Alice M.; Taylor, Graham; Wilson, Callum; McKinlay Gardner, R. J.; Love, Donald R.

    2015-01-01

    Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.

  12. Papillon–Lefevre syndrome: Reporting consanguinity as a risk factor

    PubMed Central

    Shah, Aasim Farooq; Tangade, Pradeep; Agarwal, Swatantra

    2014-01-01

    Papillon–Lefevre syndrome (PLS) is an autosomal recessive genetic disorder characterized by palmoplantar hyperkeratosis associated with severe early-onset periodontitis and premature loss of primary and permanent teeth. This report describes two cases of PLS in 28-year-old female and 16-year-old male siblings with consanguineously married parents. The patients presented to the Department of Public Health Dentistry of a dental education and research institute in India with thickening, flaking, and scaling of the skin on the palms and soles of the feet. On oral examination, the female patient presented completely resorbed maxillary and mandibular alveolar ridges with retention of only the third molars. The male patient retained only teeth 18, 13, 28, 38, and 45. Based on complete histories and clinical examination findings, a final diagnosis of PLS was made and treatment was initiated using an interdisciplinary dental approach in both cases. PMID:25057233

  13. Domestic violence and consanguineous marriages - perspective from Rawalpindi, Pakistan.

    PubMed

    Shaikh, M Ali; Kayani, A; Shaikh, I Ali

    2014-01-01

    Domestic violence is globally endemic and adversely impacts the health and economic well-being of women and society. This study used the standardized and validated assessment instrument "Woman Abuse Screening Tool" to study the prevalence of various forms of domestic violence among married women. The relationship between domestic violence and consanguineous marriage was studied using the chi-squared test. Cumulatively, 1010 married women were interviewed. Emotional abuse was the most commonly reported abuse, reported by 721 (71.4%) women as either often or sometimes, followed by sexual abuse and physical abuse, reported by 527 (52.2%) and 511 (50.6%) respectively. Being married to one's cousin did not protect married women from being abused either emotionally or physically by their husbands; thsi was statistically significant. There is a need for better understanding of the magnitude and scale of domestic violence in Pakistan by using standardized assessment tools for meaningful comparisons across different parts of the country over time.

  14. Papillon-Lefevre syndrome: Reporting consanguinity as a risk factor.

    PubMed

    Shah, Aasim Farooq; Tangade, Pradeep; Agarwal, Swatantra

    2014-07-01

    Papillon-Lefevre syndrome (PLS) is an autosomal recessive genetic disorder characterized by palmoplantar hyperkeratosis associated with severe early-onset periodontitis and premature loss of primary and permanent teeth. This report describes two cases of PLS in 28-year-old female and 16-year-old male siblings with consanguineously married parents. The patients presented to the Department of Public Health Dentistry of a dental education and research institute in India with thickening, flaking, and scaling of the skin on the palms and soles of the feet. On oral examination, the female patient presented completely resorbed maxillary and mandibular alveolar ridges with retention of only the third molars. The male patient retained only teeth 18, 13, 28, 38, and 45. Based on complete histories and clinical examination findings, a final diagnosis of PLS was made and treatment was initiated using an interdisciplinary dental approach in both cases.

  15. Genomic runs of homozygosity record population history and consanguinity.

    PubMed

    Kirin, Mirna; McQuillan, Ruth; Franklin, Christopher S; Campbell, Harry; McKeigue, Paul M; Wilson, James F

    2010-01-01

    The human genome is characterised by many runs of homozygous genotypes, where identical haplotypes were inherited from each parent. The length of each run is determined partly by the number of generations since the common ancestor: offspring of cousin marriages have long runs of homozygosity (ROH), while the numerous shorter tracts relate to shared ancestry tens and hundreds of generations ago. Human populations have experienced a wide range of demographic histories and hold diverse cultural attitudes to consanguinity. In a global population dataset, genome-wide analysis of long and shorter ROH allows categorisation of the mainly indigenous populations sampled here into four major groups in which the majority of the population are inferred to have: (a) recent parental relatedness (south and west Asians); (b) shared parental ancestry arising hundreds to thousands of years ago through long term isolation and restricted effective population size (N(e)), but little recent inbreeding (Oceanians); (c) both ancient and recent parental relatedness (Native Americans); and (d) only the background level of shared ancestry relating to continental N(e) (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan African agriculturalists), and the occasional cryptically inbred individual. Moreover, individuals can be positioned along axes representing this demographic historic space. Long runs of homozygosity are therefore a globally widespread and under-appreciated characteristic of our genomes, which record past consanguinity and population isolation and provide a distinctive record of the demographic history of an individual's ancestors. Individual ROH measures will also allow quantification of the disease risk arising from polygenic recessive effects.

  16. Consanguineous marriage and differentials in age at marriage, contraceptive use and fertility in Pakistan.

    PubMed

    Hussain, R; Bittles, A H

    1999-01-01

    Fertility rates in Pakistan have remained consistently high over the past three decades. While numerous studies have examined sociodemographic determinants, the role of biological factors, and particularly consanguinity, has received little attention, even though marriage between close biological relatives continues to be the norm in Pakistan. Reproductive behaviour among women in consanguineous (first cousin) and non-consanguineous unions was compared, using data from a 1995 study of multi-ethnic communities in Karachi and the 1990-91 Pakistan Demographic & Health Survey (PDHS). The results show that, although female age at first marriage has been gradually rising in both study samples, women in consanguineous unions married at younger ages and were less likely to use modern contraceptive methods. In the Karachi sample, women in first cousin unions experienced a higher mean number of pregnancies and also reported a higher mean number of children ever born (CEB). However, their mean number of surviving children did not differ from those born to women in non-consanguineous unions, implying higher prenatal and/or postnatal losses in couples related as first cousins. On the other hand, the PDHS showed both lower CEB values for women in consanguineous marriages and a lower number of surviving children. Given the continuing popularity of consanguineous marriage, these findings have important implications for future fertility reduction in Pakistan.

  17. Consanguinity as a determinant of reproductive behaviour and mortality in Pakistan.

    PubMed

    Bittles, A H; Grant, J C; Shami, S A

    1993-06-01

    To determine the prevalence of consanguineous marriages and estimate the effects of consanguinity on reproductive behaviour and mortality, household and hospital-based surveys were conducted in 11 cities in the Pakistan province of Punjab between 1979 and 1985. The 9520 women interviewed reported 44,474 pregnancies, with data collected on maternal and paternal ages at marriage, abortions/miscarriages, stillbirths and deaths in the first month, at 2-12 months and 2-8/10 years. Six categories of consanguineous marriage were included: double first cousin, first cousin, first cousin once removed/double second cousin, second cousin, bradari (brotherhood) and non-consanguineous. Marriages contracted between spouses related as second cousins or closer accounted for 50.3% of the total, equivalent to an average coefficient of kinship (alpha = sigma piFi) of 0.0280. Unions between close biological relatives were characterized by younger maternal and paternal ages at marriage and reduced spousal age difference, but a longer time to first delivery. Overall, they exhibited greater fertility than non-consanguineous couples. Antenatal and postnatal mortality were assessed by consanguinity and age interval. Consanguinity-associated deaths were consistently higher in the neonatal, infant and childhood periods. The consequences of these outcomes on the health of the present and future generations is assessed.

  18. Common Origin of Four Diverse Families of Large Eukaryotic DNA Viruses

    PubMed Central

    Iyer, Lakshminarayan M.; Aravind, L.; Koonin, Eugene V.

    2001-01-01

    Comparative analysis of the protein sequences encoded in the genomes of three families of large DNA viruses that replicate, completely or partly, in the cytoplasm of eukaryotic cells (poxviruses, asfarviruses, and iridoviruses) and phycodnaviruses that replicate in the nucleus reveals 9 genes that are shared by all of these viruses and 22 more genes that are present in at least three of the four compared viral families. Although orthologous proteins from different viral families typically show weak sequence similarity, because of which some of them have not been identified previously, at least five of the conserved genes appear to be synapomorphies (shared derived characters) that unite these four viral families, to the exclusion of all other known viruses and cellular life forms. Cladistic analysis with the genes shared by at least two viral families as evolutionary characters supports the monophyly of poxviruses, asfarviruses, iridoviruses, and phycodnaviruses. The results of genome comparison allow a tentative reconstruction of the ancestral viral genome and suggest that the common ancestor of all of these viral families was a nucleocytoplasmic virus with an icosahedral capsid, which encoded complex systems for DNA replication and transcription, a redox protein involved in disulfide bond formation in virion membrane proteins, and probably inhibitors of apoptosis. The conservation of the disulfide-oxidoreductase, a major capsid protein, and two virion membrane proteins indicates that the odd-shaped virions of poxviruses have evolved from the more common icosahedral virion seen in asfarviruses, iridoviruses, and phycodnaviruses. PMID:11689653

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

    SciTech Connect

    Wahlstroem, J.; Swanbeck, G.; Inerot, A.

    1994-09-01

    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.

  20. Effects of consanguineous marriages on fertility among three endogamous groups of Andhra Pradesh.

    PubMed

    Reddy, P G

    1987-01-01

    To assess interrelationships between consanguineous marriage and fertility, 3 caste groups in Andhra Pradesh--the Desuri Kapu, an affluent agricultural caste; the Devanga, an artisan caste in the middle range of the hierarchy; and the Mala, a scheduled caste at the bottom--were selected for field study. Consanguineous marriages are an essential part of the social structure in this area of southern India. A total of 2524 marriages were analyzed, of which 46% were consanguineous. 19% of consanguineous marriages were between uncle and niece, 22% were between 1st cousins, and 5% were between more distant cousins. The Devanga had the highest rate of related marriages (48%), followed by the Desuri Kapu (47%) and the Mala (41%). Higher caste individuals, and wealthier persons within each caste, are more likely to marry relatives so they can avoid splitting their properties through dowry of bride price. The consanguineous unions as a whole were significantly more fertile than nonconsanguineous unions. The mean number of pregnancies, live births, and surviving offspring was 4.85, 4.44, and 2.99, respectively, among consanguineous couples compared with 3.41, 3.32, and 2.87, respectively, among nonconsanguineous couples. Although the number of pregnancies and live births was significantly higher among consanguineous couples in all 3 castes compared with nonconsanguineous couples, the difference in the number of surviving children between consanguineous and nonconsanguineous unions was not significant among the wealthier castes. This suggests that child mortality is higher among the offspring of consanguineous unions, despite their greater wealth.

  1. Clinical and molecular characterisation of Bardet-Biedl syndrome in consanguineous populations: the power of homozygosity mapping.

    PubMed

    Abu Safieh, L; Aldahmesh, M A; Shamseldin, H; Hashem, M; Shaheen, R; Alkuraya, H; Al Hazzaa, S A F; Al-Rajhi, A; Alkuraya, F S

    2010-04-01

    Bardet-Biedl syndrome (BBS) is a ciliopathy with pleiotropic effect that manifests primarily as renal insufficiency, polydactyly, retinal dystrophy and obesity. The current phenotype-genotype correlation is insufficient to predict the likely causative mutation that makes sequencing of all 14 BBS genes an often necessary but highly complicated way to identify the underlying genetic defect in affected patients. In this study, homozygosity mapping is shown as a robust approach that is highly suited for genetically heterogeneous autosomal recessive disorders in populations in which consanguinity is prevalent. This approach allowed us to quickly identify seven novel mutations in seven families with BBS. Some of these mutations would have been missed by unguided routine sequencing, which suggests that missed mutations in known BBS genes could be more common than previously thought. This study, the largest to date on Saudi BBS families, also revealed interesting phenotypic aspects of BBS, including the first report of non-syndromic retinitis pigmentosa as a novel BBS phenotype.

  2. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    PubMed

    Jaber, Lutfi; Karim, Igbaria A; Jawdat, Abu Moch; Fausi, Mawasi; Merlob, Paul

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P < 0.001). Age and religion had no significant effect. An urgent need exists to improve the awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity).

  3. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    PubMed

    Jaber, Lutfi; Karim, Igbaria A; Jawdat, Abu Moch; Fausi, Mawasi; Merlob, Paul

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P < 0.001). Age and religion had no significant effect. An urgent need exists to improve the awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity). PMID:15050876

  4. Large family with both parents affected by distinct BRCA1 mutations: implications for genetic testing

    PubMed Central

    Sokolenko, Anna P; Voskresenskiy, Dmitry A; Iyevleva, Aglaya G; Bit-Sava, Elena M; Gutkina, Nadezhda I; Anisimenko, Maxim S; Yu Sherina, Nathalia; Mitiushkina, Nathalia V; Ulibina, Yulia M; Yatsuk, Olga S; Zaitseva, Olga A; Suspitsin, Evgeny N; Togo, Alexandr V; Pospelov, Valery A; Kovalenko, Sergey P; Semiglazov, Vladimir F; Imyanitov, Evgeny N

    2009-01-01

    Although the probability of both parents being affected by BRCA1 mutations is not negligible, such families have not been systematically described in the literature. Here we present a large breast-ovarian cancer family, where 3 sisters and 1 half-sister inherited maternal BRCA1 5382insC mutation while the remaining 2 sisters carried paternal BRCA1 1629delC allele. No BRCA1 homozygous mutations has been detected, that is consistent with the data on lethality of BRCA1 knockout mice. This report exemplifies that the identification of a single cancer-predisposing mutation within the index patient may not be sufficient in some circumstances. Ideally, all family members affected by breast or ovarian tumor disease have to be subjected to the DNA testing, and failure to detect the mutation in any of them calls for the search of the second cancer-associated allele. PMID:19338681

  5. Identification of a rhodopsin gene mutation in a large family with autosomal dominant retinitis pigmentosa.

    PubMed

    Yu, Xinping; Shi, Wei; Cheng, Lulu; Wang, Yanfang; Chen, Ding; Hu, Xuting; Xu, Jinling; Xu, Limin; Wu, Yaming; Qu, Jia; Gu, Feng

    2016-01-01

    Retinitis pigmentosa (RP) is a genetically highly heterogeneous retinal disease and one of the leading causes of blindness in the world. Next-generation sequencing technology has enormous potential for determining the genetic etiology of RP. We sought to identify the underlying genetic defect in a 35-year-old male from an autosomal-dominant RP family with 14 affected individuals. By capturing next-generation sequencing (CNGS) of 144 genes associated with retinal diseases, we identified eight novel DNA variants; however, none of them cosegregated for all the members of the family. Further analysis of the CNGS data led to identification of a recurrent missense mutation (c.403C > T, p.R135W) in the rhodopsin (RHO) gene, which cosegregated with all affected individuals in the family and was not observed in any of the unaffected family members. The p.R135W mutation has a reference single nucleotide polymorphism (SNP) ID (rs104893775), and it appears to be responsible for the disease in this large family. This study highlights the importance of examining NGS data with reference SNP IDs. Thus, our study is important for data analysis of NGS-based clinical genetic diagnoses. PMID:26794436

  6. Clinical and linkage study of a large family with simple ectopia lentis linked to FBN1

    SciTech Connect

    Edwards, M.J.; Roberts, J.; Partington, M.W.; Colley, P.W.; Hollway, G.E.; Kozman, H.M.; Mulley, J.C.

    1994-10-15

    Simple ectopia lentis (EL) was studied in a large family, by clinical examination and analysis of linkage to markers in the region of FBN1, the gene for fibrillin which causes Marfan syndrome on chromosome 15. No patient had clinical or echocardiographic evidence of Marfan syndrome, although there was a trend towards relatively longer measurements of height; lower segment; arm span; middle finger, hand, and foot length in the affected members of the family, compared with unaffected sibs of the same sex. Analysis of linkage to intragenic FBN1 markers was inconclusive because they were relatively uninformative. Construction of a multipoint background map from the CEPH reference families identified microsatellite markers linked closely to FBN1 which could demonstrate linkage of EL in this family to the FBN1 region. LINKMAP analysis detected a multipoint lod score of 5.68 at D15S119, a marker approximately 6 cM distal to FBN1, and a multipoint lod score of 5.04 at FBN1. The EL gene in this family is likely to be allelic to Marfan syndrome, and molecular characterization of the FBN1 mutation should now be possible. 25 refs., 6 figs., 2 tabs.

  7. A large multigene family codes for the polypeptides of the crystalline trichocyst matrix in Paramecium.

    PubMed Central

    Madeddu, L; Gautier, M C; Vayssié, L; Houari, A; Sperling, L

    1995-01-01

    The secretory granules (trichocysts) of Paramecium are characterized by a highly constrained shape that reflects the crystalline organization of their protein contents. Yet the crystalline trichocyst content is composed not of a single protein but of a family of related polypeptides that derive from a family of precursors by protein processing. In this paper we show that a multigene family, of unusually large size for a unicellular organism, codes for these proteins. The family is organized in subfamilies; each subfamily codes for proteins with different primary structures, but within the subfamilies several genes code for nearly identical proteins. For one subfamily, we have obtained direct evidence that the different members are coexpressed. The three subfamilies we have characterized are located on different macronuclear chromosomes. Typical 23-29 nucleotide Paramecium introns are found in one of the regions studied and the intron sequences are more variable than the surrounding coding sequences, providing gene-specific markers. We suggest that this multigene family may have evolved to assure a microheterogeneity of structural proteins necessary for morphogenesis of a complex secretory granule core with a constrained shape and dynamic properties: genetic analysis has shown that correct assembly of the crystalline core is necessary for trichocyst function. Images PMID:7579685

  8. Consanguinity and endogamy in the Netherlands: demographic and medical genetic aspects.

    PubMed

    Ten Kate, Leo P; Teeuw, Marieke E; Henneman, Lidewij; Cornel, Martina C

    2014-01-01

    This paper reviews what is currently known about the presence of consanguinity and endogamy in the Netherlands, in the past and today, and concludes with a discussion of medical genetic aspects. First geographic characteristics, the demographic history, the genetic make-up of the native population, legal aspects and the public opinion are reviewed. Then data on the prevalence of consanguinity in the native population are presented for marriages since 1840, followed by data on consanguineous marriages among immigrants from countries with a tradition of close-kin marriages. It is estimated that approximately 1% of at-risk consanguineous couples are referred to clinical genetic centres for prospective genetic counselling in the Netherlands. This picture will change dramatically if and when next-generation sequencing is introduced to identify couples at ≥ 25% risk prospectively. PMID:25060279

  9. Modernization or cultural maintenance: the practice of consanguineous marriage in Iran.

    PubMed

    Jalal Abbasi-Shavazi, Mohammad; McDonald, Peter; Hosseini-Chavoshi, Meimanat

    2008-11-01

    Consanguineous marriage has been the culturally preferred form of marriage in Iran. This paper examines the extent to which education, urbanization and changes in modes of economic production have affected the incidence of consanguineous marriage and attitudes towards consanguineous marriages. The 2002 Iran Fertility Transition Survey conducted in the four provinces of Gilan, Sistan and Baluchistan, Yazd and West Azarbaijan provides information on the degree of relationship of marriage partners from around 6550 ever-married women aged 15-49. Attitudinal data were also obtained. Overall, the level of marriage to biological relatives ranged from 23% in Gilan to 78% in Sistan and Baluchistan. The paper finds that the practice of marriage to biological relatives has remained surprisingly resilient in the face of modernizing influences and that ethnicity, province and area of residence remain important determinants. On the other hand, attitudes have shifted towards marriage with a non-relative. Anthropological research would illuminate the processes of consanguineous marriage in Iran.

  10. Consanguinity and endogamy in the Netherlands: demographic and medical genetic aspects.

    PubMed

    Ten Kate, Leo P; Teeuw, Marieke E; Henneman, Lidewij; Cornel, Martina C

    2014-01-01

    This paper reviews what is currently known about the presence of consanguinity and endogamy in the Netherlands, in the past and today, and concludes with a discussion of medical genetic aspects. First geographic characteristics, the demographic history, the genetic make-up of the native population, legal aspects and the public opinion are reviewed. Then data on the prevalence of consanguinity in the native population are presented for marriages since 1840, followed by data on consanguineous marriages among immigrants from countries with a tradition of close-kin marriages. It is estimated that approximately 1% of at-risk consanguineous couples are referred to clinical genetic centres for prospective genetic counselling in the Netherlands. This picture will change dramatically if and when next-generation sequencing is introduced to identify couples at ≥ 25% risk prospectively.

  11. Phenotype-Genotype Correlation in Wilson Disease in a Large Lebanese Family: Association of c.2299insC with Hepatic and of p. Ala1003Thr with Neurologic Phenotype

    PubMed Central

    Usta, Julnar; Wehbeh, Antonios; Rida, Khaled; El-Rifai, Omar; Estiphan, Theresa Alicia; Majarian, Tamar; Barada, Kassem

    2014-01-01

    Genotype phenotype correlations in Wilson disease (WD) are best established in homozygous patients or in compound heterozygous patients carrying the same set of mutations. We determined the clinical phenotype of patients with WD carrying the c.2298_2299insC in Exon 8 (c.2299insC) or the p. Ala1003Thr missense substitution in Exon 13 mutations in the homozygous or compound heterozygous state. We investigated 76 members of a single large Lebanese family. Their genotypes were determined, and clinical assessments were carried out for affected subjects. We also performed a literature search retrieving the phenotypes of patients carrying the same mutations of our patients in the homozygous or compound heterozygous state. There were 7 consanguineous marriages in this family and the prevalence of WD was 8.9% and of carriers of ATP7B mutation 44.7%. WD was confirmed in 9 out of 76 subjects. All 9 had the c.2299insC mutation, 5 homozygous and 4-compound heterozygous with p. Ala1003Thr. Six of our patients had hepatic, 2 had neurologic and 1 had asymptomatic phenotype. Based on our data and a literature review, clear phenotypes were reported for 38 patients worldwide carrying the c.2299insC mutation. About 53% of those have hepatic and 29% have neurologic phenotype. Furthermore, there were 10 compound heterozygous patients carrying the p. Ala1003Thr mutation. Among those, 80% having c.2299insC as the second mutation had hepatic phenotype, and all others had neurologic phenotype. We hereby report an association between the c.2299insC mutation and hepatic phenotype and between the p. Ala1003Thr mutation and neurologic phenotype. PMID:25390358

  12. Genomic Selection For Bacterial Cold Water Disease Resistance In Rainbow Trout Reveals Large Within-Family Variation That Cannot Be Exploited In Traditional Family-based Selective Breeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Selective breeding is an effective strategy to improve resistance to specific pathogens, and thus has the potential to mitigate antibiotic use in aquaculture. Large family sizes of aquaculture species permits family-based selective breeding programs, but the need for specific-pathogen-free nucleus p...

  13. Consanguineous marriage in PR China: a study in rural Man (Manchu) communities.

    PubMed

    Wang, W; Qian, Cong; Bittles, A H

    2002-01-01

    Although there is a long history of consanguineous marriage in China, information on its prevalence is very limited. The Man (Qing) dynasty ruled China for over 250 years, but no consanguinity studies have been reported on this important population. The objective of the present investigation was to determine the present-day level of consanguineous marriage in the Man community, and to compare the data with existing consanguinity information on other Chinese populations. The study was conducted in a group of 11 rural Man communities in the north-eastern Chinese province of Liaoning. Household-based interviews were conducted by local staff on 513 couples, 418 of whom were Man with another 95 Man-Han inter-ethnic marriages. Basic pedigrees were constructed to determine the biological relationship between each set of spouses. Thirty of the 418 couples were in a consanguineous union, with a mean coefficient of inbreeding alpha = 0.0012. The small population sizes of the study may have contributed to the spatial variation in the patterns of inbreeding. Across generations there was a reduction in consanguineous marriages and an increase in inter-ethnic unions, which paralleled changes in civil marriage regulations.

  14. The relationship between consanguineous marriage and death in fetus and infants

    PubMed Central

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

    2012-01-01

    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. PMID:23626609

  15. Fryns syndrome in a girl born to consanguineous parents.

    PubMed

    Schwyzer, U; Briner, J; Schinzel, A

    1987-01-01

    An overweight female newborn with multiple congenital anomalies died shortly after birth. The parents were cousins. The following abnormal findings were noted: Broad, square-shaped head with flat nose, misshapen ears, cleft palate, receding chin, short neck with additional skinfolds, disproportionately short limbs, transverse palmar creases, distal digital hypoplasia with hypoplastic finger- and toenails. Autopsy disclosed a number of further malformations including: dysplasia of the hippocampus, atypical lobation of the lungs with cystic-adenomatoid malformation of the left upper lobe, malrotation of the intestine, bilateral cystic renal dysplasia, bilateral atretic ureters plus a right accessory hydroureter, hypoplastic urinary bladder, uterus and vagina duplex and elongated, partly cystic ovaries. The pattern of malformations in this girl is very similar to that of 7 previously reported patients including two sets of siblings and one instance of parental consanguinity. All patients died shortly after birth. For proper genetic counselling and for prenatal ultrasonographic diagnosis in a further pregnancy, it is important to recognize patients with the Fryns syndrome.

  16. Clinical expression of developmental coordination disorder in a large Canadian family.

    PubMed

    Gaines, Robin; Collins, David; Boycott, Kym; Missiuna, Cheryl; Delaat, Denise; Soucie, Helen

    2008-11-01

    Previous studies of the phenotype of developmental coordination disorder (DCD) have largely concentrated on population-based samples. The present study reports on an in-depth examination of a large Canadian family with eight children, after three children who were suspected to have DCD were referred for evaluation. Subsequently, five of the six children whose motor impairments could be measured, and the mother, met the diagnostic criteria for DCD as per the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders - fourth edition. The family members diagnosed with DCD showed remarkably similar profiles of motor difficulties. Additionally, the five children diagnosed with DCD had current speech articulation difficulties, with four of them having visited speech/language pathologists; the mother had a lateral lisp. More in-depth testing for three children revealed intact intellectual, academic and language comprehension skills. Three of the children diagnosed with DCD were obese. The present report highlights familial clustering of DCD and the presence of comorbid conditions in the affected children. PMID:19436536

  17. Towards identification of an epilepsy gene in a large family with idiopathic generalized epilepsy

    SciTech Connect

    Roussear, M.; Lopes-Cendes, I.; Berkovic, S.F.

    1994-09-01

    To identify the disease gene in a large, multiplex family segregating an autosomal dominant form of idiopathic generalized epilepsy (IGE). The IGEs have been recognized for several decades as being genetically determined. However, large pedigrees with a clear Mendelian inheritance are not commonly available. This, and the presence of locus heterogeneity have been obstacles to the identification of linkage in several IGE syndromes. We have identified a large IGE kindred with fifty-eight living individuals, including 26 affecteds, showing a clear autosomal dominant inheritance with incomplete penetrance. Forty-fur informative individuals, including 23 affecteds, were selected for the linkage studies. We have chosen 200 polymorphic microsatellite markers, about 20 cM apart, throughout the human autosomes as a genome-search linkage strategy. To date, 47 markers, representing 30% of the human genome, have been excluded for linkage in the Australian kindred. As our study progresses, we will report up-to-date results.

  18. Penetrance and clinical consequences of a gross SDHB deletion in a large family.

    PubMed

    Solis, D C; Burnichon, N; Timmers, H J L M; Raygada, M J; Kozupa, A; Merino, M J; Makey, D; Adams, K T; Venisse, A; Gimenez-Roqueplo, A-P; Pacak, K

    2009-04-01

    Mutations in the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) are inherited in an autosomal dominant manner and are associated with hereditary paraganglioma (PGL) and pheochromocytoma. The phenotype of patients with SDHB point mutations has been previously described. However, the phenotype and penetrance of gross SDHB deletions have not been well characterized as they are rarely described. The objective was to describe the phenotype and estimate the penetrance of an exon 1 large SDHB deletion in one kindred. A retrospective and prospective study of 41 relatives across five generations was carried out. The main outcome measures were genetic testing, clinical presentations, plasma catecholamines and their O-methylated metabolites. Of the 41 mutation carriers identified, 11 were diagnosed with PGL, 12 were found to be healthy carriers after evaluation, and 18 were reportedly healthy based on family history accounts. The penetrance of PGL related to the exon 1 large SDHB deletion in this family was estimated to be 35% by age 40. Variable expressivity of the phenotype associated with a large exon 1 SDHB deletion was observed, including low penetrance, diverse primary PGL tumor locations, and malignant potential.

  19. Penetrance and clinical consequences of a gross SDHB deletion in a large family

    PubMed Central

    Solis, DC; Burnichon, N; Timmers, HJLM; Raygada, MJ; Kozupa, A; Merino, MJ; Makey, D; Adams, KT; Venisse, A; Gimenez-Roqueplo, A-P; Pacak, K

    2016-01-01

    Mutations in the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) are inherited in an autosomal dominant manner and are associated with hereditary paraganglioma (PGL) and pheochromocytoma. The phenotype of patients with SDHB point mutations has been previously described. However, the phenotype and penetrance of gross SDHB deletions have not been well characterized as they are rarely described. The objective was to describe the phenotype and estimate the penetrance of an exon 1 large SDHB deletion in one kindred. A retrospective and prospective study of 41 relatives across five generations was carried out. The main outcome measures were genetic testing, clinical presentations, plasma catecholamines and their O-methylated metabolites. Of the 41 mutation carriers identified, 11 were diagnosed with PGL, 12 were found to be healthy carriers after evaluation, and 18 were reportedly healthy based on family history accounts. The penetrance of PGL related to the exon 1 large SDHB deletion in this family was estimated to be 35% by age 40. Variable expressivity of the phenotype associated with a large exon 1 SDHB deletion was observed, including low penetrance, diverse primary PGL tumor locations, and malignant potential. PMID:19389109

  20. Bombay blood group: Is prevalence decreasing with urbanization and the decreasing rate of consanguineous marriage

    PubMed Central

    Mallick, Sujata; Kotasthane, Dhananjay S.; Chowdhury, Puskar S.; Sarkar, Sonali

    2015-01-01

    Context: Bombay blood group although rare is found to be more prevalent in the Western and Southern states of India, believed to be associated with consanguineous marriage. Aims: To estimate the prevalence of the Bombay blood group (Oh) in the urban population of Puducherry. To find the effect of urbanization on consanguineous marriage and to establish whether consanguinity plays a part in the prevalence of Oh group. To compare Oh group prevalence with that of other neighboring states, where population is not predominantly urban. Settings and Design: This is a descriptive study in a tertiary care hospital in Puducherry, over a period of 6 years. Materials and Methods: All blood samples showing ‘O’ group were tested with anti-H lectin. Specialized tests like Adsorption Elution Technique, inhibition assay for determination of secretor status were performed on Oh positive cases. Any history of consanguineous marriage was recorded. Statistical Analysis Used: All variables were categorical variable and percentage and proportions were calculated manually. Results: Analysis of the results of 35,497 study subjects showed that the most common group was ‘O’ group constituting 14,164 (39.90%) of subjects. Only three “Oh” that is, Bombay phenotype (0.008%) were detected. Consanguinity was observed in two cases (66.66%). Conclusions: This study shows the prevalence of Bombay blood group representing the urban population of Puducherry, to be high (0.008%) and associated with consanguineous marriage (66.66%). Thus, consanguinity is still an important risk factor present, even in an urban population in Southern India. PMID:26420929

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

    PubMed

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

    2000-02-01

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

  2. Identification of a GJA3 Mutation in a Large Family with Bilateral Congenital Cataract.

    PubMed

    Li, Bin; Liu, Yuying; Liu, Yaning; Guo, Hui; Hu, Zhengmao; Xia, Kun; Jin, Xuemin

    2016-03-01

    The congenital cataract has been a clinically important cause of impaired vision development, making up about 10% of the cases of childhood blindness. Mutations of more than 40 genes have been identified causing congenital cataract with Mendelian inheritance, which indicated that it has an extremely high genetic heterogeneity. In this study, we recruited a large congenital cataract family and identified a missense mutation (c.143A>G: p.E48G) within gap junction protein alpha-3 (GJA3) gene in the proband using whole exome sequencing. Subsequent Sanger sequencing of this mutation in all family members revealed that this mutation cosegregated with the phenotype in the family with full penetrance. Our study identified a mutation in GJA3 that correlated with congenital cataract phenotype, which was not reported previously, and would be of benefit to the diagnosis of this genetic disorder. This finding expands the mutation spectrum of GJA3 and provides useful information for further study of the molecular pathogenesis of congenital cataract.

  3. A large family of divergent Drosophila odorant-binding proteins expressed in gustatory and olfactory sensilla.

    PubMed

    Galindo, K; Smith, D P

    2001-11-01

    We identified a large family of putative odorant-binding protein (OBP) genes in the genome of Drosophila melanogaster. Some of these genes are present in large clusters in the genome. Most members are expressed in various taste organs, including gustatory sensilla in the labellum, the pharyngeal labral sense organ, dorsal and ventral cibarial organs, as well as taste bristles located on the wings and tarsi. Some of the gustatory OBPs are expressed exclusively in taste organs, but most are expressed in both olfactory and gustatory sensilla. Multiple binding proteins can be coexpressed in the same gustatory sensillum. Cells in the tarsi that express OBPs are required for normal chemosensation mediated through the leg, as ablation of these cells dramatically reduces the sensitivity of the proboscis extension reflex to sucrose. Finally, we show that OBP genes expressed in the pharyngeal taste sensilla are still expressed in the poxneuro genetic background while OBPs expressed in the labellum are not. These findings support a broad role for members of the OBP family in gustation and olfaction and suggest that poxneuro is required for cell fate determination of labellar but not pharyngeal taste organs. PMID:11729153

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

    SciTech Connect

    Desai, Nishita; Mukhopadhyaya, Biswarup

    2009-09-01

    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.

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

    PubMed

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

    2000-08-01

    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.

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

    PubMed

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

    2013-02-01

    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.

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

    PubMed Central

    2013-01-01

    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 Δ12 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 Δ12-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 Δ12 position

  8. An empirical analysis of the effects of consanguineous marriages on economic development.

    PubMed

    Bildirici, Melike; Kökdener, Meltem; Ersin, Oezgür ömer

    2010-01-01

    In this study, development experiences toward economic development are investigated to provide an alternative analysis of economic development, human capital, and genetic inheritance in the light of consanguineous marriages. The countries analyzed in the study are discussed in accordance with consanguineous marriage practices and classified by their per capita gross domestic product (GDP) growth. A broad range of countries are analyzed in the study. Arab countries that experienced high rates of growth in their gross national income during the twentieth century but failed to fulfill adequate development measures as reflected in the growth in national income, countries undergoing transition from tight government regulation to free market democracy, and African nations that have experienced complications in the process of development show important differences in the process of economic development. It is shown that the countries that have reached high average development within the context of per capita GDP have overcome problems integral to consanguineous marriage.

  9. Transcriptome Sequencing of a Large Human Family Identifies the Impact of Rare Noncoding Variants

    PubMed Central

    Li, Xin; Battle, Alexis; Karczewski, Konrad J.; Zappala, Zach; Knowles, David A.; Smith, Kevin S.; Kukurba, Kim R.; Wu, Eric; Simon, Noah; Montgomery, Stephen B.

    2014-01-01

    Recent and rapid human population growth has led to an excess of rare genetic variants that are expected to contribute to an individual’s genetic burden of disease risk. To date, much of the focus has been on rare protein-coding variants, for which potential impact can be estimated from the genetic code, but determining the impact of rare noncoding variants has been more challenging. To improve our understanding of such variants, we combined high-quality genome sequencing and RNA sequencing data from a 17-individual, three-generation family to contrast expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) within this family to eQTLs and sQTLs within a population sample. Using this design, we found that eQTLs and sQTLs with large effects in the family were enriched with rare regulatory and splicing variants (minor allele frequency < 0.01). They were also more likely to influence essential genes and genes involved in complex disease. In addition, we tested the capacity of diverse noncoding annotation to predict the impact of rare noncoding variants. We found that distance to the transcription start site, evolutionary constraint, and epigenetic annotation were considerably more informative for predicting the impact of rare variants than for predicting the impact of common variants. These results highlight that rare noncoding variants are important contributors to individual gene-expression profiles and further demonstrate a significant capability for genomic annotation to predict the impact of rare noncoding variants. PMID:25192044

  10. The changing pattern of consanguinity in a selected region of the Israeli Arab community.

    PubMed

    Sharkia, Rajach; Zaid, Muhamad; Athamna, Abed; Cohen, Dani; Azem, Abdussalam; Zalan, Abdelnaser

    2008-01-01

    The prevalence of consanguinity within the Israeli Arab community is relatively high, and is associated with high rates of inherited disorders that lead to a high frequency of morbidity and mortality. Data on consanguinity between couples were recorded during two periods (1980-1985 and 2000-2004) in relation to socioeconomic status of 4 selected villages. Two of the villages (A and B) are known to have high socioeconomic status, and the other two (C and D) are known to have low socioeconomic status. The average incidence of consanguineous marriages has slightly decreased from 33.1% in the first period to 25.9% in the second period (P = 0.0218) in all of the 4 villages. Marriages between first cousins showed a more significant decrease, from 23.9% in the first period to 13.6% in the second period (P < 0.0001). The average consanguinity rates of villages A and B were found to decrease from 22.3 to 16.2% respectively (P < 0.001) between the two observation periods, whereas those of villages C and D were found to decrease from 42.3 to 37.2%, (P < 0.001) during the same two periods. Thus, there has been a change in the pattern of consanguinity within the selected Israeli Arab villages, between the two study periods. This change seems to correlate with the sociodemographic status of the villages. Therefore, improving the socioeconomic status of the villages, as well as implementation of proper health education programs, is expected to have a positive effect in reducing consanguinity.

  11. [The economic-financial sustainability of the Family Health Strategy in large municipalities].

    PubMed

    Portela, Gustavo Zoio; Ribeiro, José Mendes

    2011-03-01

    The universalization of basic care and commitment budget of the Ministry of Health with the Family Health Strategy (ESF) through new systematic financing incentives have been highlighted in the Brazilian health policy scenario. One of the great problems observed is the expansion of the strategy for large urban centres. This paper studies the economic-financial sustainability of ESF in Brazilian municipalities of more than 100 thousand inhabitants according to some selected indicators, considering the geographical region to which they belong, their population size and participation in Project for the Expansion and Consolidation Family Health (Proesf). Municipalities belonging to the Southeast region, more developed of the country, have on average better economic-financial performance, but lower average values of coverage of ESF. Municipalities from the North and Northeast, with the lowest average for economic-financial sustainability indicators, were the ones that made more effort to developments in the period. Thus, we observed the dynamics between bigger fiscal capacity and budgetary commitment with the Health Sector for biggest municipalities and in more economically developed regions, and greater vulnerability and dependence of federative transferences for municipalities with less people, in less developed areas.

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

    PubMed

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

    2007-09-01

    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.

  13. Large scale in silico identification of MYB family genes from wheat expressed sequence tags.

    PubMed

    Cai, Hongsheng; Tian, Shan; Dong, Hansong

    2012-10-01

    The MYB proteins constitute one of the largest transcription factor families in plants. Much research has been performed to determine their structures, functions, and evolution, especially in the model plants, Arabidopsis, and rice. However, this transcription factor family has been much less studied in wheat (Triticum aestivum), for which no genome sequence is yet available. Despite this, expressed sequence tags are an important resource that permits opportunities for large scale gene identification. In this study, a total of 218 sequences from wheat were identified and confirmed to be putative MYB proteins, including 1RMYB, R2R3-type MYB, 3RMYB, and 4RMYB types. A total of 36 R2R3-type MYB genes with complete open reading frames were obtained. The putative orthologs were assigned in rice and Arabidopsis based on the phylogenetic tree. Tissue-specific expression pattern analyses confirmed the predicted orthologs, and this meant that gene information could be inferred from the Arabidopsis genes. Moreover, the motifs flanking the MYB domain were analyzed using the MEME web server. The distribution of motifs among wheat MYB proteins was investigated and this facilitated subfamily classification.

  14. SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia

    PubMed Central

    Nickerson, Sarah L.; Marquis-Nicholson, Renate; Claxton, Karen; Ashton, Fern; Leong, Ivone U. S.; Prosser, Debra O.; Love, Jennifer M.; George, Alice M.; Taylor, Graham; Wilson, Callum; McKinlay Gardner, R. J.; Love, Donald R.

    2015-01-01

    Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias. PMID:27600236

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

    PubMed

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

    2013-02-01

    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.

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

    ERIC Educational Resources Information Center

    Online Submission, 2007

    2007-01-01

    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…

  17. The Role of Family Environment in Depressive Symptoms among University Students: A Large Sample Survey in China

    PubMed Central

    Yang, Yanjie; Chen, Lu; Qiu, Xiaohui; Qiao, Zhengxue; Zhou, Jiawei; Pan, Hui; Ban, Bo; Zhu, Xiongzhao; He, Jincai; Ding, Yongqing; Bai, Bing

    2015-01-01

    Objective To explore the relationship between family environment and depressive symptoms and to evaluate the influence of hard and soft family environmental factors on depression levels in a large sample of university students in China. Methods A multi-stage stratified sampling procedure was used to select 6,000 participants. The response rate was 88.8%, with 5,329 students completing the Beck Depression Inventory (BDI) and the Family Environment Scale Chinese Version (FES-CV), which was adapted for the Chinese population. Differences between the groups were tested for significance by the Student’s t-test; ANOVA was used to test continuous variables. The relationship between soft family environmental factors and BDI were tested by Pearson correlation analysis. Hierarchical linear regression analysis was conducted to model the effects of hard environmental factors and soft environmental factors on depression in university students. Results A total of 11.8% of students scored above the threshold of moderate depression(BDI≧14). Hard family environmental factors such as parent relationship, family economic status, level of parental literacy and non-intact family structure were associated with depressive symptoms. The soft family environmental factors—conflict and control—were positively associated with depression, while cohesion was negatively related to depressive symptom after controlling for other important associates of depression. Hierarchical regression analysis indicated that the soft family environment correlates more strongly with depression than the hard family environment. Conclusions Soft family environmental factors—especially cohesion, conflict and control—appeared to play an important role in the occurrence of depressive symptoms. These findings underline the significance of the family environment as a source of risk factors for depression among university students in China and suggest that family-based interventions and improvement are very

  18. Impact of consanguinity on cardio-metabolic health and other diseases: findings from an Afro-Indian tribal community.

    PubMed

    Bhasin, Prerna; Kapoor, Satwanti

    2015-04-01

    Numerous anthropological reports have indicated consanguineous marriage in populous Asian countries, but the overall impact of first cousin marriage on survival and health of specific communities has rarely been reported. The aim of the study was to estimate risks for various complex diseases in the progeny of consanguineous parents. A cross-sectional study was conducted among 222 women among Siddis, a particularly vulnerable tribal group in the state of Gujarat, India, who are Sunni Muslims by faith. The Siddis are not part of the original Negrito element of India. They are descendants of Africans from Northeast and East Africa who were brought to India as slaves, soldiers, or servants. The degree of consanguinity between each female and her spouse and the degree of consanguinity between their parents and proband's grandparents were recorded with the help of pedigrees. The results showed that the rate of consanguinity in the present generation was 49 % (N = 109), higher than preceding generations. A significant association was observed between women's age, educational level, occupational status, consanguineous parents, and consanguinity. Socioeconomic status and consanguinity showed U-shaped associations. Nearly three times odds for cardio-metabolic risks (2.65 odds ratio (OR) for heart diseases, 2.44 OR for diabetes mellitus, and 2.62 OR for hypertension) have been contracted in the progeny of consanguineous marriage in the parental generation. The risk of cardio-metabolic diseases is higher in offspring of consanguineous couples, and there is a significant increase in the prevalence of common adult diseases.

  19. Family.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1985-01-01

    This document contains the fourth volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of the family and delinquency. "The Family and Delinquency" (LaMar T. Empey) systematically reviews and weighs the evidence to support prominent theories on the origins of…

  20. Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families.

    PubMed

    Kang, Peter; Mariapun, Shivaani; Phuah, Sze Yee; Lim, Linda Shushan; Liu, Jianjun; Yoon, Sook-Yee; Thong, Meow Keong; Mohd Taib, Nur Aishah; Yip, Cheng Har; Teo, Soo-Hwang

    2010-11-01

    Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4-28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2. PMID:20617377

  1. Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families.

    PubMed

    Kang, Peter; Mariapun, Shivaani; Phuah, Sze Yee; Lim, Linda Shushan; Liu, Jianjun; Yoon, Sook-Yee; Thong, Meow Keong; Mohd Taib, Nur Aishah; Yip, Cheng Har; Teo, Soo-Hwang

    2010-11-01

    Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4-28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2.

  2. Consanguinity: A Risk Factor for Preterm Birth at Less Than 33 Weeks’ Gestation

    PubMed Central

    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

    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. PMID:20978088

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

    ERIC Educational Resources Information Center

    Abu-Rabia, Salim; Maroun, Lateefeh

    2005-01-01

    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 in…

  4. Prevalence of consanguineous marriages among shi'a populations of Lebanon.

    PubMed

    El-Kheshen, Ghadir; Saadat, Mostafa

    2013-09-01

    In genetics, a consanguineous marriage means union between couples who are related as second cousins or closer. The present cross-sectional study was carried out in order to illustrate the prevalence and types of consanguineous marriages in the Shi'a population living in widespread territories in Lebanon including the Bekaa Valley, the south of Lebanon and the southern suburb of Beirut. Data on types of marriages were collected using a simple questionnaire. The total number of couples in the study was 1203. Consanguineous marriage was classified by the degree of relationship between couples. The overall frequency of consanguinity was found to be 28.4%, with first cousin marriages (21.3%) being the most common type followed by first cousins once removed (5.5%), then double first cousins (0.8%). The frequencies of second cousin and beyond second cousin marriages were the same at 0.4% of all the marriages. The mean inbreeding coefficient (α) was estimated at about 0.0161 for the population. There were no significant differences between the three studied territories for frequencies of different types of marriages (p>0.1), nor were there significant differences between the rural and urban areas (p>0.1).

  5. Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency.

    PubMed

    Rivoisy, Claire; Gérard, Laurence; Boutboul, David; Malphettes, Marion; Fieschi, Claire; Durieu, Isabelle; Tron, François; Masseau, Agathe; Bordigoni, Pierre; Alric, Laurent; Haroche, Julien; Hoarau, Cyrille; Bérézné, Alice; Carmagnat, Maryvonnick; Mouillot, Gael; Oksenhendler, Eric

    2012-02-01

    The DEFI study has collected clinical data and biological specimens from kindreds with CVID. Patients with demonstrated parental consanguinity (cCVID group) were compared to patients without parental consanguinity (ncCVID). A total of 24 of the 436 patients with CVID had consanguineous parents. Age at first symptoms and age at diagnosis were comparable in the two groups. Some complications were more frequent in cCVID patients: splenomegaly (62.5% vs. 29%; p = 0.001), granulomatous disease (29% vs. 12%; p = 0.02), and bronchiectasis (58% vs. 29%; p = 0.003). A high incidence of opportunistic infections was also observed in this population (29% vs. 5%; p < 0.001). Distribution of B-cell subsets were similar in the two groups. Naïve CD4+ T cells were decreased in cCVID patients (15% vs. 28%; p < 0.001), while activated CD4 + CD95+ (88% vs. 74%; p = 0.002) and CD8 + HLA-DR + T cells (47% vs. 31%; p < 0.001) were increased in these patients when compared to ncCVID patients. Parental consanguinity is associated with an increased risk of developing severe clinical complications in patients with CVID. Most of these patients presented with severe T-cell abnormalities and should be considered with a diagnosis of late-onset combined immune deficiency (LOCID). Systematic investigation for parental consanguinity in patients with CVID provides useful information for specific clinical care and genetic screening. PMID:22002594

  6. Complete complement deficiency in a large cohort of familial systemic lupus erythematosus

    PubMed Central

    Aggarwal, Rachna; Sestak, Andrea L; Souza, Anil D’; Dillon, Skyler P.; Namjou, Bahram; Scofield, R Hal

    2010-01-01

    Genetic complete deficiency of the early complement components such as C1, C2 and C4 commonly results in a monogenetic form of systemic lupus erythematosus (SLE). However, previous studies have examined groups of complete complement deficient subjects for SLE, while a familial SLE cohort has not been studied for deficiencies of complement. Thus, we undertook the present study to determine the frequency of hereditary complete complement deficiencies among families with two or more SLE patients. All SLE patients from 544 such families had CH50 determined. Medical records were examined for past CH50 values. There were 66 individuals in whom all available CH50 values were zero. All but four of these had an SLE-affected relative with a non-zero CH50; thus, these families did not have monogenic complement deficient related SLE. The four remaining SLE-affected subjects were in fact two sets of siblings in which 3 of the 4 SLE patients had onset of disease at <18 years of age. Both patients in one of these families had been determined to have C4 deficiency, while the other family had no clinical diagnosis of complement deficiency. In this second family, one of the SLE patients had had normal C4 and C3 values, indicating that either C1q or C2 deficiency was possible. Thus, only 2 of 544 SLE families had definite or possible complement deficiency; however, 1 of 7 families in which all SLE patients had pediatric onset and 2 of 85 families with at least 1 pediatric-onset SLE patent had complete complement deficiency. SLE is found commonly among families with hereditary complement deficiency but the reverse is not true. Complete complement deficiency is rare among families with two or more SLE patients, but is concentrated among families with onset of SLE prior to age 18. PMID:19910391

  7. Patient perception and knowledge of acetaminophen in a large family medicine service.

    PubMed

    Herndon, Christopher M; Dankenbring, Dawn M

    2014-06-01

    The use of acetaminophen is currently under increased scrutiny by the US Food and Drug Administration (FDA) due to the risk of intentional and more concerning, unintentional overdose-related hepatotoxicity. Acetaminophen is responsible for an estimated 48% of all acute liver failure diagnoses. The purpose of this study is to evaluate patient perception and knowledge of the safe use and potential toxicity of acetaminophen-containing products. The authors conducted a descriptive, 2-week study using a convenience sample from a large family medicine clinic waiting room. Survey questions assessed ability to identify acetaminophen, knowledge of the current recommended maximum daily dose, respondent acetaminophen use patterns, common adverse effects associated with acetaminophen, and respondent self-reported alcohol consumption. Acetaminophen safety information was provided to all persons regardless of participation in the study. Of the 102 patients who chose to participate, 79% recognized acetaminophen as a synonym of Tylenol, whereas only 9% identified APAP as a frequently used abbreviation. One third of respondents thought acetaminophen was synonymous with ibuprofen and naproxen. Approximately one fourth of patients correctly identified the then maximum recommended daily acetaminophen dose of 4 g. Seventy-eight percent of patients correctly identified hepatotoxicity as the most common serious adverse effect. We conclude that patient deficiencies in knowledge of acetaminophen recognition, dosing, and toxicity warrant public education by health professionals at all levels of interaction. Current initiatives are promising; however, further efforts are required.

  8. Revisiting Myosin Families Through Large-scale Sequence Searches Leads to the Discovery of New Myosins

    PubMed Central

    Pasha, Shaik Naseer; Meenakshi, Iyer; Sowdhamini, Ramanathan

    2016-01-01

    Myosins are actin-based motor proteins involved in many cellular movements. It is interesting to study the evolutionary patterns and the functional attributes of various types of myosins. Computational search algorithms were performed to identify putative myosin members by phylogenetic analysis, sequence motifs, and coexisting domains. This study is aimed at understanding the distribution and the likely biological functions of myosins encoded in various taxa and available eukaryotic genomes. We report here a phylogenetic analysis of around 4,064 myosin motor domains, built entirely from complete or near-complete myosin repertoires incorporating many unclassified, uncharacterized sequences and new myosin classes, with emphasis on myosins from Fungi, Haptophyta, and other Stramenopiles, Alveolates, and Rhizaria (SAR). The identification of large classes of myosins in Oomycetes, Cellular slime molds, Choanoflagellates, Pelagophytes, Eustigmatophyceae, Fonticula, Eucoccidiorida, and Apicomplexans with novel myosin motif variants that are conserved and thus presumably functional extends our knowledge of this important family of motor proteins. This work provides insights into the distribution and probable function of myosins including newly identified myosin classes.

  9. Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality.

    PubMed

    Belet, Stefanie; Fieremans, Nathalie; Yuan, Xuan; Van Esch, Hilde; Verbeeck, Jelle; Ye, Zhaohui; Cheng, Linzhao; Brodsky, Brett R; Hu, Hao; Kalscheuer, Vera M; Brodsky, Robert A; Froyen, Guy

    2014-03-01

    The phosphatidylinositol glycan class A (PIGA) protein is a member of the glycosylphosphatidylinositol anchor pathway. Germline mutations in PIGA located at Xp22.2 are thought to be lethal in males. However, a nonsense mutation in the last coding exon was recently described in two brothers with multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) who survived through birth likely because of the hypomorphic nature of the truncated protein, but died in their first weeks of life. Here, we report on a frameshift mutation early in the PIGA cDNA (c.76dupT; p.Y26Lfs*3) that cosegregates with the disease in a large family diagnosed with a severe syndromic form of X-linked intellectual disability. Unexpectedly, CD59 surface expression suggested the production of a shorter PIGA protein with residual functionality. We provide evidence that the second methionine at position 37 may be used for the translation of a 36 amino acids shorter PIGA. Complementation assays confirmed that this shorter PIGA cDNA was able to partially rescue the surface expression of CD59 in a PIGA-null cell line. Taken together, our data strongly suggest that the early frameshift mutation in PIGA produces a truncated hypomorph, which is sufficient to rescue the lethality in males but not the MCAHS2-like phenotype.

  10. Wiskott–Aldrich syndrome: review and report of a large family

    PubMed Central

    Stiehm, E. R.; McIntosh, R. M.

    1967-01-01

    Wiskott–Aldrich syndrome is a sex-linked recessive antibody-deficiency syndrome characterized by thrombocytopenia, eczema and increased susceptibility to infection. All forms of therapy are notably unsuccessful and these patients succumb in the first decade. Three cases of this syndrome are presented from a large family in which nine male infants have succumbed with manifestations of this disease. Two of the infants died at ages 10 months and 4 years respectively. A third child is alive at age 2. Serial quantitative immune globulin studies performed in two cases demonstrated markedly elevated γA, decreased γM and normal γG; levels of γM were initially normal but fell progressively as γA levels increased. The low levels of γM are probably a factor in their low or absent isoagglutinins, poor response to injected antigens, and increased susceptibility to infection; elevated γA levels may indicate immunologic unresponsiveness and/or a compensatory mechanism for the defect in γM synthesis. In two of these patients prolonged trials (17 and 23 months) of periodic plasma infusions (15 ml/kg at 6-week intervals), accompanied by γ-globulin injections (0·1 ml/kg) were undertaken. Although no remarkable effects on the platelets or their resistance to infection was noted, we feel that some benefit might have accrued and that further trails are indicated. PMID:4166240

  11. Revisiting Myosin Families Through Large-scale Sequence Searches Leads to the Discovery of New Myosins

    PubMed Central

    Pasha, Shaik Naseer; Meenakshi, Iyer; Sowdhamini, Ramanathan

    2016-01-01

    Myosins are actin-based motor proteins involved in many cellular movements. It is interesting to study the evolutionary patterns and the functional attributes of various types of myosins. Computational search algorithms were performed to identify putative myosin members by phylogenetic analysis, sequence motifs, and coexisting domains. This study is aimed at understanding the distribution and the likely biological functions of myosins encoded in various taxa and available eukaryotic genomes. We report here a phylogenetic analysis of around 4,064 myosin motor domains, built entirely from complete or near-complete myosin repertoires incorporating many unclassified, uncharacterized sequences and new myosin classes, with emphasis on myosins from Fungi, Haptophyta, and other Stramenopiles, Alveolates, and Rhizaria (SAR). The identification of large classes of myosins in Oomycetes, Cellular slime molds, Choanoflagellates, Pelagophytes, Eustigmatophyceae, Fonticula, Eucoccidiorida, and Apicomplexans with novel myosin motif variants that are conserved and thus presumably functional extends our knowledge of this important family of motor proteins. This work provides insights into the distribution and probable function of myosins including newly identified myosin classes. PMID:27597808

  12. Revisiting Myosin Families Through Large-scale Sequence Searches Leads to the Discovery of New Myosins.

    PubMed

    Pasha, Shaik Naseer; Meenakshi, Iyer; Sowdhamini, Ramanathan

    2016-01-01

    Myosins are actin-based motor proteins involved in many cellular movements. It is interesting to study the evolutionary patterns and the functional attributes of various types of myosins. Computational search algorithms were performed to identify putative myosin members by phylogenetic analysis, sequence motifs, and coexisting domains. This study is aimed at understanding the distribution and the likely biological functions of myosins encoded in various taxa and available eukaryotic genomes. We report here a phylogenetic analysis of around 4,064 myosin motor domains, built entirely from complete or near-complete myosin repertoires incorporating many unclassified, uncharacterized sequences and new myosin classes, with emphasis on myosins from Fungi, Haptophyta, and other Stramenopiles, Alveolates, and Rhizaria (SAR). The identification of large classes of myosins in Oomycetes, Cellular slime molds, Choanoflagellates, Pelagophytes, Eustigmatophyceae, Fonticula, Eucoccidiorida, and Apicomplexans with novel myosin motif variants that are conserved and thus presumably functional extends our knowledge of this important family of motor proteins. This work provides insights into the distribution and probable function of myosins including newly identified myosin classes. PMID:27597808

  13. Large genomic rearrangement of BRCA1 and BRCA2 genes in familial breast cancer patients in Korea.

    PubMed

    Cho, Ja Young; Cho, Dae-Yeon; Ahn, Sei Hyun; Choi, Su-Youn; Shin, Inkyung; Park, Hyun Gyu; Lee, Jong Won; Kim, Hee Jeong; Yu, Jong Han; Ko, Beom Seok; Ku, Bo Kyung; Son, Byung Ho

    2014-06-01

    We screened large genomic rearrangements of the BRCA1 and BRCA2 genes in Korean, familial breast cancer patients. Multiplex ligation-dependent probe amplification assay was used to identify BRCA1 and BRCA2 genomic rearrangements in 226 Korean familial breast cancer patients with risk factors for BRCA1 and BRCA2 mutations, who previously tested negative for point mutations in the two genes. We identified only one large deletion (c.4186-1593_4676-1465del) in BRCA1. No large rearrangements were found in BRCA2. Our result indicates that large genomic rearrangement in the BRCA1 and BRCA2 genes does not seem like a major determinant of breast cancer susceptibility in the Korean population. A large-scale study needs to validate our result in Korea.

  14. A large deletion/insertion-induced frameshift mutation of the androgen receptor gene in a family with a familial complete androgen insensitivity syndrome.

    PubMed

    Cong, Peikuan; Ye, Yinghui; Wang, Yue; Lu, Lingping; Yong, Jing; Yu, Ping; Joseph, Kimani Kagunda; Jin, Fan; Qi, Ming

    2012-06-01

    Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disorder with a normal 46, XY karyotype caused by abnormality of the androgen receptor (AR) gene. One Chinese family consisting of the proband and 5 other members with complete androgen insensitivity syndrome (CAIS) was investigated. Mutation analysis by DNA sequencing on all 8 exons and flanking intron regions of the AR gene revealed a unique large deletion/insertion mutation in the family. A 287 bp deletion and 77 bp insertion (c.933_1219delins77) mutation at codon 312 resulted in a frameshift which caused a premature stop (p.Phe312Aspfs*7) of polypeptide formation. The proband's mother and grandmother were heterozygous for the mutant allele. The proband's father, uncle and grandfather have the normal allele. From the pedigree constructed from mutational analysis of the family, it is revealed that the probably pathogenic mutation comes from the maternal side.

  15. Consanguineous marriage in an urban area of Saudi Arabia: rates and adverse health effects on the offspring.

    PubMed

    al-Abdulkareem, A A; Ballal, S G

    1998-02-01

    The objective of this cross-sectional study was to determine the pattern and time trend of consanguineous marriage and its adverse health effects on the offspring in Dammam city, Eastern Province, in the Kingdom of Saudi Arabia. This city is known to attract Saudis from different parts of the country because it is in the heart of this industrial region. Five primary health care centers were randomly selected from different sectors of the city in addition to the city's only Maternity and Children's Hospital. For inclusion in the study a wife must have at least one pregnancy that terminated in either full term liveborn baby, still birth, or abortion. A total of 1307 ever-married Saudis completed a pre-structured questionnaire during an interview. The rate of consanguineous marriage was 52.0% with an average inbreeding coefficient of 0.0312. First-cousin marriages were the commonest (39.3%) of all matings. The consanguineous groups had a significantly higher number of pregnancies. The mean birth weight of the offspring of consanguineous couples was not statistically significant being less than that of the non-consanguineous. However, within the consanguineous groups the more closely related couples had smaller babies on average. No significant differences were noted for the rates of inherited diseases and reproductive wastage. The rate of consanguineous marriage in this city was high and so was the inbreeding coefficient. These figures place this nation among the countries with a high rate of consanguineous marriages. A nationwide study to determine accurately the relationship between consanguinity and inherited diseases has much to commend it.

  16. Clinical, histopathologic, and genetic investigation in two large families with dentinogenesis imperfecta type II.

    PubMed

    Malmgren, B; Lindskog, S; Elgadi, A; Norgren, S

    2004-04-01

    Dentinogenesis imperfecta (DI) type II, an inherited disorder affecting dentin, has been linked to mutations in the dentin sialophosphoprotein ( DSPP) gene on chromosome 4q21. The gene product is cleaved into two dentin-specific matrix proteins, dentin sialoprotein (DSP) and dentin phosphoprotein. The aim of this investigation was to study genotypes and phenotypes in two affected families with special reference to clinical, radiographic, and histopathologic manifestations. Seven affected members of Family A and five of Family B were documented clinically and radiographically; 14 and 10 teeth, respectively, were available for histopathologic investigation and prepared for ground sections, which were assessed semiquantitatively for dysplastic manifestations in the dentin according to the scoring system, dysplastic dentin score (DDS). Venous blood samples were collected from six affected and ten unaffected members of Family A, and from eight affected and six unaffected members of Family B. Genomic DNA was extracted and used for sequence analyses. The two families presented with different missense mutations. An Arg68Trp missense mutation in the DSP part of the gene was revealed in all six analyzed affected individuals in Family A. This mutation was not present in any of the ten healthy members. In Family B, an Ala15Val missense mutation involving the last residue of the signal peptide was found in all eight affected but in none of the six healthy members. The clinical and radiographic disturbances and DDS were more severe in Family B. The data indicate the presence of a genotype-phenotype correlation in DI type II.

  17. Familial pheochromocytoma, hypercalcemia, and von Hippel-Lindau disease. A ten year study of a large family.

    PubMed

    Atuk, N O; McDonald, T; Wood, T; Carpenter, J T; Walzak, M P; Donaldson, M; Gillenwater, J Y

    1979-05-01

    Long-term epidemiological and laboratory studies were carried out in a kindred with familial pheochromocytoma associated with von Hippel-Lindau disease. Thirteen members were affected by the syndrome and the trait appears to be transmitted in an autosomal dominant fashion. Of 13 patients, 7 had pheochromocytoma alone. Of the remaining six patients, one had pheochromocytoma combined with von Hippel-Lindau disease, four had pheochromocytoma with retinal disease only, and a single patient had a retinal lesion without pheochromocytoma. In four patients, pheochromocytoma antedated the development of retinal lesions. Ten members also had mild hypercalcemia without accompanying elevations of PTH in the 4 patients in whom this was determined. In all, hypercalcemia was corrected with removal of tumors, and no patient had a return of hypercalcemia in the absence of recurrent increases in urinary catecholamines. The clinical presentations in 12 patients varied markedly, as did their urinary excretion rates of norepinephrine, epinephrine and their metabolites. However, an analysis of the data revealed significant correlations not previously described between the urinary excretion of free catecholamines (norepinephrine plus epinephrine), blood pressure, the free catecholamine content of the tumor and the age of the patient. Urinary excretion of free norepinephrine plus epinephrine appear to be decreased with advancing age (p less than 0.001). Both systolic and diastolic blood pressures and the age of the patient were inversely correlated (p less than 0.01). A significant inverse relationship between the tumor content of free catecholamines and the age of the patients was, although to a lesser degree, also present (p less than 0.05). As a whole, the size of the tumors and their norepinephrine content were not correlated. We present a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the

  18. Familiality of Co-existing ADHD and Tic Disorders: Evidence from a Large Sibling Study

    PubMed Central

    Roessner, Veit; Banaschewski, Tobias; Becker, Andreas; Buse, Judith; Wanderer, Sina; Buitelaar, Jan K.; Sergeant, Joseph A.; Sonuga-Barke, Edmund J.; Gill, Michael; Manor, Iris; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Steinhausen, Hans-Christoph; Faraone, Steven V.; Asherson, Philip; Rothenberger, Aribert

    2016-01-01

    Background: The association of attention-deficit/hyperactivity disorder (ADHD) and tic disorder (TD) is frequent and clinically important. Very few and inconclusive attempts have been made to clarify if and how the combination of ADHD+TD runs in families. Aim: To determine the first time in a large-scale ADHD sample whether ADHD+TD increases the risk of ADHD+TD in siblings and, also the first time, if this is independent of their psychopathological vulnerability in general. Methods: The study is based on the International Multicenter ADHD Genetics (IMAGE) study. The present sub-sample of 2815 individuals included ADHD-index patients with co-existing TD (ADHD+TD, n = 262) and without TD (ADHD–TD, n = 947) as well as their 1606 full siblings (n = 358 of the ADHD+TD index patients and n = 1248 of the ADHD-TD index patients). We assessed psychopathological symptoms in index patients and siblings by using the Strength and Difficulties Questionnaire (SDQ) and the parent and teacher Conners' long version Rating Scales (CRS). For disorder classification the Parental Account of Childhood Symptoms (PACS-Interview) was applied in n = 271 children. Odds ratio with the GENMOD procedure (PROCGENMOD) was used to test if the risk for ADHD, TD, and ADHD+TD in siblings was associated with the related index patients' diagnoses. In order to get an estimate for specificity we compared the four groups for general psychopathological symptoms. Results: Co-existing ADHD+TD in index patients increased the risk of both comorbid ADHD+TD and TD in the siblings of these index patients. These effects did not extend to general psychopathology. Interpretation: Co-existence of ADHD+TD may segregate in families. The same holds true for TD (without ADHD). Hence, the segregation of TD (included in both groups) seems to be the determining factor, independent of further behavioral problems. This close relationship between ADHD and TD supports the clinical approach to carefully assess ADHD in any case

  19. Consanguineous Marital Union Resulting in a Progeny of Whistling-face Syndrome and Hemophilia: A Case Report.

    PubMed

    Gurjar, Vivek; Gurjar, Minal

    2015-04-01

    Many different types of genetic disorders are noted to be prevalent among consanguineous progeny. Although the most common type of consanguineous union in all major societies is between first cousins, the importance of customary influences is apparent from variations in the specific types of first-cousin marriages contracted. Epidemiological data for the prevalence of whistling-face syndrome (WFS) are not available, but less than a hundred cases reported in the literature are noted. We are presenting a case where a consanguineous marriage resulted in two of their children presenting with WFS and one with hemophilia.

  20. Consanguineous Marital Union Resulting in a Progeny of Whistling-face Syndrome and Hemophilia: A Case Report.

    PubMed

    Gurjar, Vivek; Gurjar, Minal

    2015-04-01

    Many different types of genetic disorders are noted to be prevalent among consanguineous progeny. Although the most common type of consanguineous union in all major societies is between first cousins, the importance of customary influences is apparent from variations in the specific types of first-cousin marriages contracted. Epidemiological data for the prevalence of whistling-face syndrome (WFS) are not available, but less than a hundred cases reported in the literature are noted. We are presenting a case where a consanguineous marriage resulted in two of their children presenting with WFS and one with hemophilia. PMID:25954077

  1. Characterization of the p16 gene in the mouse: Evidence for a large gene family

    SciTech Connect

    Fountain, J.W.; Giendening, J.M.; Flores, J.F.

    1994-09-01

    The p16 gene product is an inhibitor of the cyclin-dependent kinase 4 (CDK4)/cyclin D complex. When uninhibited, the CDK4/cyclin D complex participates in the phosphorylation of the retinoblastoma (RB) protein and renders it inactive. Upon inactivation of the RB protein, transition from the G{sub 1} to the S phase of mitosis occurs and results in cellular proliferation. Thus, p16 is presumed to act as a negative regulator of cell growth by preventing the phosphorylation, and thereby subsequent inactivation, of RB by CDK4/cyclin D. Recently, the p16 gene (also known as the multiple tumor suppressor 1 (MTS1) gene) has been mapped to chromosome 9p21 and found to be deleted or mutated in a number of tumor cell lines. These findings support the role of p16 as a growth inhibitor or tumor suppressor gene and suggest that the mutation of this gene may have global implications in carcinogenesis. We have chosen to test the functional significance of p16 mutations in vivo through the generation of a mouse mutant for p16. In preparation for this undertaking, eight apparently independent (as judged by restriction enzyme digestion and differential hybridization) mouse genomic embryonic stem cell clones have been identified using exon 2 from the human p16 gene as a probe. The identification of these multiple nonoverlapping clones was not entirely surprising since the reduced stringency hybridization of a zoo blot with the same probe also revealed 10-15 positive EcoRI fragments in all species tested, including human, monkey, cow, dog, cat, rabbit, hamster, mouse, chicken and D. melanogaster. Taken together, these findings suggest that the p16 gene is a member of a large gene family. The location of these genomic clones, as well as their potential expression in the mouse, is currently under investigation.

  2. Febrile convulsions in selected large families: a single-major-locus mode of inheritance?

    PubMed

    Maher, J; McLachlan, R S

    1997-02-01

    As part of a genetic linkage study of febrile convulsions, families with at least four members with the disorder were identified. By applying known principles of human inheritance, possible modes of transmission of febrile convulsions and factors which might impede progress in understanding their inheritance were analyzed. In eight families, 75 of 333 members had febrile convulsions. Inheritance of the disorder occurred in 43, 51, and 46% of children, siblings and all first-degree relatives of probands respectively. Vertical transmission occurred through three to four generations, including from male to male. In these families with multiple affected members, the findings support an autosomal dominant mode of inheritance of febrile convulsions.

  3. Migration as a determinant of marriage pattern: preliminary report on consanguinity among Afghans.

    PubMed

    Wahab, Abdul; Ahmad, Mahmud; Akram Shah, Syed

    2006-05-01

    Two sample populations, one refugee and one resident, were studied. The frequencies of consanguineous marriages came out to be 49.8%and 55.4%, respectively, for the refugees and the residents. Caste endogamy was dominant both in the residents and the refugees. The mean coefficient of inbreeding was calculated to be 0.0303 for the refugee population and 0.0332 for the resident population samples. First cousin marriage was the dominant type of marriage in both samples; father's brother's daughter (FBD) marriage was more frequent among the refugees while mother's brother's daughter(MBD) marriage was more frequent among the residents. Education has no decreasing effect on the incidence of consanguineous marriages. A significant difference in the pattern of marriages in the refugees is observed after the Saur Revolution of 1979. PMID:16613618

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

    PubMed

    Haycock, Camille; Wahl, Carol

    2013-01-01

    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

  5. Novel homozygous PANK2 mutation identified in a consanguineous Chinese pedigree with pantothenate kinase-associated neurodegeneration

    PubMed Central

    Li, Yan-Fang; Li, Hong-Fu; Zhang, Yan-Bin; Wu, Ji-Min

    2016-01-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive neurodegenerative disorder resulting from pantothenate kinase 2 (PANK2) gene mutations. It is clinically characterized by early onset of extrapyramidal symptoms, with or without pigmentary retinopathy, optic atrophy and acanthocytosis. The specific radiographic appearance of PKAN is the eye-of-the-tiger sign. However, there are few studies regarding PKAN patients of Chinese Han ancestry. In the present study, a Chinese 20-year-old female with an 8-year history of unsteady walking and involuntary movements is described. Brain magnetic resonance imaging revealed eye-of-the-tiger sign. Following sequencing of PANK2, a novel homozygous c.863C>T (p.P288L) mutation was identified in the patient and heterozygous c.863C>T was identified in her consanguineous parents. The absence of this mutation in the 1000 Genomes database, The Exome Aggregation Consortium, and 200 controls demonstrated that this mutation was probably pathogenic for PKAN in this family. In addition, the PANK2 c.863C>T mutation was predicted to be deleterious by SIFT, disease causing by Mutation Taster and probably damaging by PolyPhen2. PMID:27446545

  6. A novel mutation in the C7orf11 gene causes nonphotosensitive trichothiodystrophy in a multiplex highly consanguineous kindred.

    PubMed

    Pode-Shakked, Ben; Marek-Yagel, Dina; Greenberger, Shoshana; Pode-Shakked, Naomi; Pras, Elon; Barzilai, Aviv; Yassin, Saeed; Sidi, Yechezkel; Anikster, Yair

    2015-12-01

    Trichothiodystrophy (TTD), also known as sulfur-deficient brittle hair syndrome, is a rare autosomal recessive multisystem disorder, which manifests with brittle hair, mental retardation, ichthyosis and decreased fertility. Mutations in the TTDN1 (C7orf11) gene have been shown to cause a nonphotosensitive type of trichothiodystrophy. We report of a 19 years old male, born to consanguineous parents of Arab-Muslim descent, who presented due to severe renal failure, but exhibited additional unique features, including developmental delay, mental retardation, splenomegaly, pancytopenia, hypogonadism and brittle hair. Following the clinical diagnosis of nonphotosensitive TTD, sequencing of the coding exons of C7orf11 was performed and revealed the patient to be homozygous for a novel c.505dupA mutation. As the severe renal failure following which the proband was referred to our care is not typically characteristic of this disorder, its significance is discussed. Molecular diagnosis of this highly affected family should enable genetic counseling and prenatal diagnosis for future pregnancies. PMID:26518168

  7. A study of consanguineous marriage as a risk factor for developing comitant strabismus.

    PubMed

    Bagheri, Mansooreh; Farvardin, Majid; Saadat, Mostafa

    2015-04-01

    Inheritance has an important role in the etiology of comitant strabismus. Consanguineous marriage is a leading factor in birth defects in which inheritance has a role. The aim of this study is to reveal if consanguineous marriage increases the risk of developing comitant strabismus. We included 461 patients who underwent primary surgery for comitant strabismus in Shiraz University Khalili Hospital (Fars province, southern Iran) between years 2003 and 2013 in our study. All the patients were living in Shiraz, Iran. Patients were categorized into the following 4 groups: (1) intermittent or constant exotropia, (2) infantile esotropia, (3) non-accommodative acquired esotropia, and (4) accommodative acquired esotropia. A total of 421 healthy children who were born in Shiraz, at the same period of time, were also studied as a control group. Presence and type of the consanguineous marriages were evaluated in the parents of the patients and control group by a questionnaire. Mean of inbreeding coefficient (α) was calculated in each group of patients and was compared with those of control group. The proportion of parental first cousin marriage was 37.7 and 23.5 % among patient and control groups. The mean of inbreeding coefficients (α) were 0.0236, 0.0283, 0.0288, and 0.0236 in four groups of the patients, respectively. The mean of inbreeding coefficient was 0.0263 in total patients, which was significantly higher than 0.0164 of control group (T = 5.27, df = 880, P < 0.001). Patients with non-accommodative acquired esotropia had the highest mean of inbreeding coefficient (α) (0.0288). It seems that recessive form of inheritance plays an important role in the etiology of comitant strabismus. Modified screening programs may be needed for earlier detection of strabismus in the offspring of consanguineous couples.

  8. Retrospective analysis of cohort database: Phenotypic variability in a large dataset of patients confirmed to have homozygous familial hypercholesterolemia

    PubMed Central

    Raal, Frederick J.; Sjouke, Barbara; Hovingh, G. Kees; Isaac, Barton F.

    2016-01-01

    These data describe the phenotypic variability in a large cohort of patients confirmed to have homozygous familial hypercholesterolemia. Herein, we describe the observed relationship of treated low-density lipoprotein cholesterol with age. We also overlay the low-density lipoprotein receptor gene (LDLR) functional status with these phenotypic data. A full description of these data is available in our recent study published in Atherosclerosis, “Phenotype Diversity Among Patients With Homozygous Familial Hypercholesterolemia: A Cohort Study” (Raal et al., 2016) [1]. PMID:27182539

  9. Consanguinity and endogamy in Northern Tunisia and its impact on non-syndromic deafness.

    PubMed

    Ben Arab, Saida; Masmoudi, Saber; Beltaief, Najeh; Hachicha, Slah; Ayadi, Hammadi

    2004-07-01

    Deafness is an important health problem in the Tunisian population, especially in isolates where the prevalence ranges from 2 to 8%. To evaluate the effect of inbred unions on deafness, a study was conducted on 5,020 individuals (160 are deaf) between 2000 and 2002 in the North of Tunisia. The coefficient of inbreeding for all individuals and the levels of inbreeding in ten districts were computed. The higher levels were obtained in the rural districts. Our study revealed that geographic isolation, social traditions, and parental involvement in mode selection all contribute to increase consanguinity in these regions. The mean inbreeding seems to be similar to those estimated in highly inbred isolates in the world. The relative risk of the 35delG mutation, the single most frequent allele for non-syndromic recessive deafness in Tunisia, was estimated from the observed inbreeding coefficient and found to be 10.76 (SD 7.74) for first-cousin marriages, which are the most common form of consanguineous marriage encountered. Our knowledge of the risk rate of deafness and our understanding of consanguinity is required for the prevention of genetic deafness in the Tunisian population.

  10. Atypical Features in a Large Turkish Family Affected with Friedreich Ataxia

    PubMed Central

    Cevik, Betul; Aksoy, Durdane; Sahbaz, E. Irmak; Basak, A. Nazli

    2016-01-01

    Here, we describe the clinical features of several members of the same family diagnosed with Friedreich ataxia (FRDA) and cerebral lesions, demyelinating neuropathy, and late-age onset without a significant cardiac involvement and presenting with similar symptoms, although genetic testing was negative for the GAA repeat expansion in one patient of the family. The GAA repeat expansion in the frataxin gene was shown in all of the family members except in a young female patient. MRI revealed arachnoid cysts in two patients; MRI was consistent with both cavum septum pellucidum-cavum vergae and nodular signal intensity increase in one patient. EMG showed demyelinating sensorimotor polyneuropathy in another patient. The GAA expansion-negative 11-year-old female patient had mental-motor retardation, epilepsy, and ataxia. None of the patients had significant cardiac symptoms. Description of FRDA families with different ethnic backgrounds may assist in identifying possible phenotypic and genetic features of the disease. Furthermore, the genetic heterogeneity observed in this family draws attention to the difficulty of genetic counseling in an inbred population and to the need for genotyping all affected members before delivering comprehensive genetic counseling.

  11. Atypical Features in a Large Turkish Family Affected with Friedreich Ataxia.

    PubMed

    Kurt, Semiha; Cevik, Betul; Aksoy, Durdane; Sahbaz, E Irmak; Gundogdu Eken, Aslı; Basak, A Nazli

    2016-01-01

    Here, we describe the clinical features of several members of the same family diagnosed with Friedreich ataxia (FRDA) and cerebral lesions, demyelinating neuropathy, and late-age onset without a significant cardiac involvement and presenting with similar symptoms, although genetic testing was negative for the GAA repeat expansion in one patient of the family. The GAA repeat expansion in the frataxin gene was shown in all of the family members except in a young female patient. MRI revealed arachnoid cysts in two patients; MRI was consistent with both cavum septum pellucidum-cavum vergae and nodular signal intensity increase in one patient. EMG showed demyelinating sensorimotor polyneuropathy in another patient. The GAA expansion-negative 11-year-old female patient had mental-motor retardation, epilepsy, and ataxia. None of the patients had significant cardiac symptoms. Description of FRDA families with different ethnic backgrounds may assist in identifying possible phenotypic and genetic features of the disease. Furthermore, the genetic heterogeneity observed in this family draws attention to the difficulty of genetic counseling in an inbred population and to the need for genotyping all affected members before delivering comprehensive genetic counseling. PMID:27668106

  12. Atypical Features in a Large Turkish Family Affected with Friedreich Ataxia

    PubMed Central

    Cevik, Betul; Aksoy, Durdane; Sahbaz, E. Irmak; Basak, A. Nazli

    2016-01-01

    Here, we describe the clinical features of several members of the same family diagnosed with Friedreich ataxia (FRDA) and cerebral lesions, demyelinating neuropathy, and late-age onset without a significant cardiac involvement and presenting with similar symptoms, although genetic testing was negative for the GAA repeat expansion in one patient of the family. The GAA repeat expansion in the frataxin gene was shown in all of the family members except in a young female patient. MRI revealed arachnoid cysts in two patients; MRI was consistent with both cavum septum pellucidum-cavum vergae and nodular signal intensity increase in one patient. EMG showed demyelinating sensorimotor polyneuropathy in another patient. The GAA expansion-negative 11-year-old female patient had mental-motor retardation, epilepsy, and ataxia. None of the patients had significant cardiac symptoms. Description of FRDA families with different ethnic backgrounds may assist in identifying possible phenotypic and genetic features of the disease. Furthermore, the genetic heterogeneity observed in this family draws attention to the difficulty of genetic counseling in an inbred population and to the need for genotyping all affected members before delivering comprehensive genetic counseling. PMID:27668106

  13. Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies.

    PubMed

    Grewal, Prabhjit K; McLaughlan, Jennifer M; Moore, Christopher J; Browning, Claudia A; Hewitt, Jane E

    2005-10-01

    The Large(myd) mouse has a loss-of-function mutation in the putative glycosyltransferase gene Large. Mutations in the human homolog (LARGE) have been described in a form of congenital muscular dystrophy (MDC1D). Other genes (POMT1, POMGnT1, fukutin, and FKRP) that encode known or putative glycosylation enzymes are also causally associated with human congenital muscular dystrophies. All these diseases are associated with hypoglycosylation of the membrane protein alpha-dystroglycan (alpha-DG) and consequent loss of extracellular ligand binding. Hence, they are termed dystroglycanopathies. A paralogous gene for LARGE (LARGE2 or GYLTL1B) may also have a role in DG glycosylation. Using database interrogation and reverse-transcriptase polymerase chain reaction (RT-PCR), we identified vertebrate orthologs of each of these LARGE genes in many vertebrates, including human, mouse, dog, chicken, zebrafish, and pufferfish. However, within invertebrate genomes, we were able to identify only single homologs. We suggest that vertebrate LARGE orthologs be referred to as LARGE1. RT-PCR, dot-blot, and northern analysis indicated that LARGE2 has a more restricted tissue-expression profile than LARGE1. Using epitope-tagged proteins, we show that both LARGE1 and LARGE2 localize to the Golgi apparatus. The high similarity between the LARGE paralogs suggests that LARGE2 may also act on DG. Overexpression of LARGE2 in mouse C2C12 myoblasts results in increased glycosylation of alpha-DG accompanied by an increase in laminin binding. Thus, there may be functional redundancy between LARGE1 and LARGE2. Consistent with this idea, we show that alpha-DG is still fully glycosylated in kidney (a tissue that expresses a high level of LARGE2 mRNA) of Large(myd) mutant mice. PMID:15958417

  14. On the genetics of mandibular prognathism: analysis of large European noble families.

    PubMed Central

    Wolff, G; Wienker, T F; Sander, H

    1993-01-01

    Mandibular prognathism is assumed to be a polygenic trait in the vast majority of cases. In a few families, this phenotype and perhaps a syndrome with a broader spectrum of facial anomalies seems to be determined by a single dominant gene of very low frequency (McKusick No *176700). The phenotype is known to have occurred independently in several European noble families. We constructed a pedigree comprising 13 of these families with 409 members in 23 generations in which mandibular prognathism has been segregating. Obviously, the presumed dominant gene is not fully penetrant in the heterozygous state. Pedigree analysis using the Elston-Stewart algorithm yields a maximum likelihood estimate (MLE) of p = 0.955 (SE 0.038) of the penetrance parameter. Images PMID:8445614

  15. Screening of male breast cancer and of breast-ovarian cancer families for BRCA2 mutations using large bifluorescent amplicons

    PubMed Central

    Pages, S; Caux, V; Stoppa-Lyonnet, D; Tosi, M

    2001-01-01

    41 breast cancer or breast-ovarian cancer families, including 12 families with at least one affected first-degree male relative, were screened for mutations in the BRCA2 gene. Mutations had not been found in the BRCA1 gene of these families. Chemical cleavage of Mismatch was used to identify nucleotide changes within large PCR products (average size 1.2 kb) that carried strand-specific fluorescent end-labels. 15 amplicons were sufficient to scan 18 exons, including the large exon 11. The remaining 9 small exons were examined by Denaturing Gradient Gel Electrophoresis. The high sensitivity of this approach was documented by the detection, in these 41 patients, of all 9 exonic single nucleotide polymorphisms reported with heterozygosity >0.1. Truncating BRCA2 mutations were found in 7 of the 41 families. 3 of them were in the group of 12 families comprising cases of male breast cancer. Since the methods used here have no bias for particular types of mutations, these data confirm the high proportion of frameshifts among mutations in BRCA2. However, relevant single nucleotide substitutions were also found: one resulting in a stop codon and another one, present in a male patient, was the previously reported change Asp2723His, that affects a highly conserved region of the BRCA2 protein. This study indicates a BRCA2 contribution of 10% (95% CI 2.5–17.5) to our original cohort of 59 breast-ovarian cancer families, whereas the contribution of BRCA1 had been estimated at 46% (95% CI 33–59). © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11207042

  16. [Multiple endocrine neoplasia type 1: genetic study of a large family].

    PubMed

    Orellana, C; Palasí, R; Martínez, F; Ponce, J L; Gil Sanz, J; Sancho Fornos, S; Prieto, F

    1999-03-01

    Multiple endocrine neoplasia syndrome type 1 (MEN-1) is an inherited disorder characterised by the predisposition of the cells from parathyroid glands, endocrine pancreas and adenohypophysis to develop neoplasms. We report the genetic study of an extended family with at least 8 affected patients and 10 putative carriers of a mutation in MEN-1 gene. One intragenic (Asp418 GAC-->GAT), and five flanking markers were characterised in the family by PCR amplification and polyachrylamide gel electrophoresis. Association of the disease to MEN-1 gene was confirmed for this family: all the affected members show a haplotype in common. Three patients at risk were diagnosed as non-carriers, since they have not inherited that haplotype. The remaining seven members, presymptomatic carriers, are included in a follow-up protocol. The genetic study of families segregating MEN-1 syndrome are useful in avoiding indiscriminate follow-up determinations to those members who have not received the genetic predisposition to develop any of the manifestations of the syndrome. Segregation analysis with linked markers is useful, under certain circumstances, to perform such type of studies. PMID:10207847

  17. Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family

    PubMed Central

    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

    2012-01-01

    Summary Bromodomains (BRDs) are protein interaction modules that specifically recognize ε-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

  18. Moxidectin and the avermectins: Consanguinity but not identity

    PubMed Central

    Prichard, Roger; Ménez, Cécile; Lespine, Anne

    2012-01-01

    The avermectins and milbemycins contain a common macrocyclic lactone (ML) ring, but are fermentation products of different organisms. The principal structural difference is that avermectins have sugar groups at C13 of the macrocyclic ring, whereas the milbemycins are protonated at C13. Moxidectin (MOX), belonging to the milbemycin family, has other differences, including a methoxime at C23. The avermectins and MOX have broad-spectrum activity against nematodes and arthropods. They have similar but not identical, spectral ranges of activity and some avermectins and MOX have diverse formulations for great user flexibility. The longer half-life of MOX and its safety profile, allow MOX to be used in long-acting formulations. Some important differences between MOX and avermectins in interaction with various invertebrate ligand-gated ion channels are known and could be the basis of different efficacy and safety profiles. Modelling of IVM interaction with glutamate-gated ion channels suggest different interactions will occur with MOX. Similarly, profound differences between MOX and the avermectins are seen in interactions with ABC transporters in mammals and nematodes. These differences are important for pharmacokinetics, toxicity in animals with defective transporter expression, and probable mechanisms of resistance. Resistance to the avermectins has become widespread in parasites of some hosts and MOX resistance also exists and is increasing. There is some degree of cross-resistance between the avermectins and MOX, but avermectin resistance and MOX resistance are not identical. In many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates. These similarities and differences should be appreciated for optimal decisions about parasite control, delaying, managing or reversing resistances, and also for appropriate anthelmintic combination. PMID:24533275

  19. Evolution of a large, conserved, and syntenic gene family in insects.

    PubMed

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

    2012-02-01

    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.

  20. Dividing the Large Glycoside Hydrolase Family 43 into Subfamilies: a Motivation for Detailed Enzyme Characterization

    PubMed Central

    Mewis, Keith; Lombard, Vincent

    2016-01-01

    The rapid rise in DNA sequencing has led to an expansion in the number of glycoside hydrolase (GH) families. The GH43 family currently contains α-l-arabinofuranosidase, β-d-xylosidase, α-l-arabinanase, and β-d-galactosidase enzymes for the debranching and degradation of hemicellulose and pectin polymers. Many studies have revealed finer details about members of GH43 that necessitate the division of GH43 into subfamilies, as was done previously for the GH5 and GH13 families. The work presented here is a robust subfamily classification that assigns over 91% of all complete GH43 domains into 37 subfamilies that correlate with conserved sequence residues and results of biochemical assays and structural studies. Furthermore, cooccurrence analysis of these subfamilies and other functional modules revealed strong associations between some GH43 subfamilies and CBM6 and CBM13 domains. Cooccurrence analysis also revealed the presence of proteins containing up to three GH43 domains and belonging to different subfamilies, suggesting significant functional differences for each subfamily. Overall, the subfamily analysis suggests that the GH43 enzymes probably display a hitherto underestimated variety of subtle specificity features that are not apparent when the enzymes are assayed with simple synthetic substrates, such as pNP-glycosides. PMID:26729713

  1. The Bacterial Intimins and Invasins: A Large and Novel Family of Secreted Proteins

    PubMed Central

    Tsai, Jennifer C.; Yen, Ming-Ren; Castillo, Rostislav; Leyton, Denisse L.; Henderson, Ian R.; Saier, Milton H.

    2010-01-01

    Background Gram-negative bacteria have developed a limited repertoire of solutions for secreting proteins from the cytoplasmic compartment to the exterior of the cell. Amongst the spectrum of secreted proteins are the intimins and invasins (the Int/Inv family; TC# 1.B.54) which are characterized by an N-terminal β-barrel domain and a C-terminal surface localized passenger domain. Despite the important role played by members of this family in diseases mediated by several species of the Enterobacteriaceae, there has been little appreciation for the distribution and diversity of these proteins amongst Gram-negative bacteria. Furthermore, there is little understanding of the molecular events governing secretion of these proteins to the extracellular milieu. Principal Findings In silico approaches were used to analyze the domain organization and diversity of members of this secretion family. Proteins belonging to this family are predominantly associated with organisms from the γ-proteobacteria. Whilst proteins from the Chlamydia, γ-, β- and ε-proteobacteria possess β-barrel domains and passenger domains of various sizes, Int/Inv proteins from the α-proteobacteria, cyanobacteria and chlorobi possess only the predicted β-barrel domains. Phylogenetic analyses revealed that with few exceptions these proteins cluster according to organismal type, indicating that divergence occurred contemporaneously with speciation, and that horizontal transfer was limited. Clustering patterns of the β-barrel domains correlate well with those of the full-length proteins although the passenger domains do so with much less consistency. The modular subdomain design of the passenger domains suggests that subdomain duplication and deletion have occurred with high frequency over evolutionary time. However, all repeated subdomains are found in tandem, suggesting that subdomain shuffling occurred rarely if at all. Topological predictions for the β-barrel domains are presented. Conclusion

  2. Estimating the degree of identity by descent in consanguineous couples.

    PubMed

    Carr, Ian M; Markham, Sir Alexander F; Pena, Sérgio D J

    2011-12-01

    In some clinical and research settings, it is often necessary to identify the true level of "identity by descent" (IBD) between two individuals. However, as the individuals become more distantly related, it is increasingly difficult to accurately calculate this value. Consequently, we have developed a computer program that uses genome-wide SNP genotype data from related individuals to estimate the size and extent of IBD in their genomes. In addition, the software can compare a couple's IBD regions with either the autozygous regions of a relative affected by an autosomal recessive disease of unknown cause, or the IBD regions in the parents of the affected relative. It is then possible to calculate the probability of one of the couple's children suffering from the same disease. The software works by finding SNPs that exclude any possible IBD and then identifies regions that lack these SNPs, while exceeding a minimum size and number of SNPs. The accuracy of the algorithm was established by estimating the pairwise IBD between different members of a large pedigree with varying known coefficients of genetic relationship (CGR).

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

    PubMed Central

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

    2007-01-01

    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. PMID:17428316

  4. Identification of recurrent and novel mutations in TULP1 in Pakistani families with early-onset retinitis pigmentosa

    PubMed Central

    Ajmal, Muhammad; Khan, Muhammad Imran; Micheal, Shazia; Ahmed, Waqas; Shah, Ashfa; Venselaar, Hanka; Bokhari, Habib; Azam, Aisha; Waheed, Nadia Khalida; Collin, Rob W.J.; den Hollander, Anneke I.; Qamar, Raheel

    2012-01-01

    Purpose To identify the genetic defects underlying retinitis pigmentosa (RP) in Pakistani families. Methods Genome-wide high-density single-nucleotide-polymorphism microarray analysis was performed using the DNA of nine affected individuals from two large families with multiple consanguineous marriages. Data were analyzed to identify homozygous regions that are shared by affected sibs in each family. Sanger sequencing was performed for genes previously implicated in autosomal recessive RP and allied retinal dystrophies that resided in the identified homozygous regions. Probands from both families underwent fundus examination and electroretinogram measurements. Results The tubby-like protein 1 gene (TULP1) was present in the largest homozygous region in both families. Sequence analysis identified a previously reported mutation (c.1138A>G; p.Thr380Ala) in one family and a novel pathogenic variant (c.1445G>A; p.Arg482Gln) in the other family. Both variants were found to be present in a homozygous state in all affected individuals, were heterozygous present in the unaffected parents, and heterozygous present or absent in normal individuals. Affected individuals of both families showed an early-onset form of RP. Conclusions Homozygosity mapping, combined with candidate-gene analysis, successfully identified genetic defects in TULP1 in two large Pakistani families with early-onset retinitis pigmentosa. PMID:22665969

  5. SLE like syndrome and functional deficiency of C1q in members of a large family.

    PubMed

    Hannema, A J; Kluin-Nelemans, J C; Hack, C E; Eerenberg-Belmer, A J; Mallée, C; van Helden, H P

    1984-01-01

    Two sisters and a brother from one family are described whose sera were deficient in haemolytic complement function. This defect was restored by addition of purified C1q. In their sera, C1q like material was found, whereas C1r and C1s were normal or increased in concentration, as were the other complement components tested. All three had suffered from glomerulonephritis during childhood. A renal biopsy in the brother recently disclosed a membranous glomerulopathy stage 1; otherwise, he is apparently healthy. In both sisters, a systemic lupus erythematosus like disease became manifest at the age of 20 and 23, respectively, resulting in the death of one of them. In the serum of these three family members, the C1q like material was antigenically deficient compared with normal C1q and had, on sucrose gradient analysis, a molecular weight of approximately 65,000 daltons. It did not bind to C1r and C1s. Binding of the dysfunctional C1q to aggregated human gammaglobulin could be demonstrated. On double immunodiffusion analysis, the abnormal C1q was identical with reduced and alkylated C1q. The possible structure of the abnormal C1q molecule is discussed.

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

    SciTech Connect

    Belal, S.; Ben Hamida, C.; Hentati, F.; Ben Hamida, M. ); Panayides, K.; Ioannou, P.; MIddleton, L.T. ); Sirugo, G.; Koenig, S.; Mandel, J.L ); Beckmann, J. )

    1992-12-01

    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.

  7. Maternal intrusiveness, family financial means, and anxiety across childhood in a large multiphase sample of community youth.

    PubMed

    Cooper-Vince, Christine E; Pincus, Donna B; Comer, Jonathan S

    2014-01-01

    Intrusive parenting has been positively associated with child anxiety, although examinations of this relationship to date have been largely confined to middle to upper middle class families and have rarely used longitudinal designs. With several leading interventions for child anxiety emphasizing the reduction of parental intrusiveness, it is critical to determine whether the links between parental intrusiveness and child anxiety broadly apply to families of all financial means, and whether parental intrusiveness prospectively predicts the development of child anxiety. This study employed latent growth curve analysis to evaluate the interactive effects of maternal intrusiveness and financial means on the developmental trajectory of child anxiety from 1st grade to age 15 in 1,121 children (50.7 % male) and their parents from the NICHD SECCYD. The overall model was found to provide good fit, revealing that early maternal intrusiveness and financial means did not impact individual trajectories of change in child anxiety, which were stable from 1st to 5th grade, and then decrease from 5th grade to age 15. Cross-sectional analyses also examined whether family financial means moderated contemporaneous relationships between maternal intrusiveness and child anxiety in 3rd and 5th grades. The relationship between maternal intrusiveness and child anxiety was moderated by family financial means for 1st graders, with stronger links found among children of lower family financial means, but not for 3rd and 5th graders. Neither maternal intrusiveness nor financial means in 1st grade predicted subsequent changes in anxiety across childhood. Findings help elucidate for whom and when maternal intrusiveness has the greatest link with child anxiety and can inform targeted treatment efforts.

  8. Maternal intrusiveness, family financial means, and anxiety across childhood in a large multiphase sample of community youth

    PubMed Central

    Cooper-Vince, Christine E.; Pincus, Donna B.; Comer, Jonathan S.

    2013-01-01

    Intrusive parenting has been positively associated with child anxiety, although examinations of this relationship to date have been largely confined to middle to upper middle class families and have rarely used longitudinal designs. With several leading interventions for child anxiety emphasizing the reduction of parental intrusiveness, it is critical to determine whether the links between parental intrusiveness and child anxiety broadly apply to families of all financial means, and whether parental intrusiveness prospectively predicts the development of child anxiety. This study employed latent growth curve analysis to evaluate the interactive effects of maternal intrusiveness and financial means on the developmental trajectory of child anxiety from 1st grade to age 15 in 1,121 children (50.7% male) and their parents from the NICHD SECCYD. The overall model was found to provide good fit, revealing that early maternal intrusiveness and financial means did not impact individual trajectories of change in child anxiety, which were stable from 1st to 5th grade, and then decrease from 5th grade to age 15. Cross-sectional analyses also examined whether family financial means moderated contemporaneous relationships between maternal intrusiveness and child anxiety in 3rd and 5th grades. The relationship between maternal intrusiveness and child anxiety was moderated by family financial means for 1st graders, with stronger links found among children of lower family financial means, but not for 3rd and 5th graders. Neither maternal intrusiveness nor financial means in 1st grade predicted subsequent changes in anxiety across childhood. Findings help elucidate for whom and when maternal intrusiveness has the greatest link with child anxiety and can inform targeted treatment efforts. PMID:23929005

  9. Exome Sequencing Identifies a Dominant TNNT3 Mutation in a Large Family with Distal Arthrogryposis

    PubMed Central

    Daly, Sarah B.; Shah, Hitesh; O'Sullivan, James; Anderson, Beverley; Bhaskar, Sanjeev; Williams, Simon; Al-Sheqaih, Nada; Mueed Bidchol, Abdul; Banka, Siddharth; Newman, William G.; Girisha, Katta M.

    2014-01-01

    Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the distal limb joints without a neuromuscular disease. Mutations in at least 8 different genes have been shown to cause DA. Here, we report a 4-generation Indian family with 18 affected members presenting variable features of camptodactyly, brachydactyly, syndactyly, decreased flexion palmar creases, ulnar deviation of the hands, sandal gaps and club feet. We undertook exome sequencing of 3 distantly related affected individuals. Bioinformatics filtering revealed a known pathogenic missense mutation c.188G>A (p.Arg63His) in TNNT3 in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability. This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders. PMID:25337069

  10. Exome Sequencing of 75 Individuals from Multiply Affected Coeliac Families and Large Scale Resequencing Follow Up

    PubMed Central

    Mistry, Vanisha; Bockett, Nicholas A.; Levine, Adam P.; Mirza, Muddassar M.; Hunt, Karen A.; Ciclitira, Paul J.; Hummerich, Holger; Neuhausen, Susan L.; Simpson, Michael A.; Plagnol, Vincent; van Heel, David A.

    2015-01-01

    Coeliac disease (CeD) is a highly heritable common autoimmune disease involving chronic small intestinal inflammation in response to dietary wheat. The human leukocyte antigen (HLA) region, and 40 newer regions identified by genome wide association studies (GWAS) and dense fine mapping, account for ∼40% of the disease heritability. We hypothesized that in pedigrees with multiple individuals with CeD rare [minor allele frequency (MAF) <0.5%] mutations of larger effect size (odds ratios of ∼ 2–5) might exist. We sequenced the exomes of 75 coeliac individuals of European ancestry from 55 multiply affected families. We selected interesting variants and genes for further follow up using a combination of: an assessment of shared variants between related subjects, a model-free linkage test, and gene burden tests for multiple, potentially causal, variants. We next performed highly multiplexed amplicon resequencing of all RefSeq exons from 24 candidate genes selected on the basis of the exome sequencing data in 2,248 unrelated coeliac cases and 2,230 controls. 1,335 variants with a 99.9% genotyping call rate were observed in 4,478 samples, of which 939 were present in coding regions of 24 genes (Ti/Tv 2.99). 91.7% of coding variants were rare (MAF <0.5%) and 60% were novel. Gene burden tests performed on rare functional variants identified no significant associations (p<1×10−3) in the resequenced candidate genes. Our strategy of sequencing multiply affected families with deep follow up of candidate genes has not identified any new CeD risk mutations. PMID:25635822

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

    PubMed

    Gu, Xun; Wang, Yufeng; Gu, Jianying

    2002-06-01

    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.

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

    PubMed

    Gu, Xun; Wang, Yufeng; Gu, Jianying

    2002-06-01

    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

  13. [Computerized family reconstitution on a large data-base: the SOREP system].

    PubMed

    Bouchard, G; Roy, R; Casgrain, B

    1986-01-01

    This article outlines a new system for computerized family reconstitution. It has been developed in the last 10 years by a multidisciplinary team of Quebec researchers belonging to the Inter-University Research Center on Populations (SOREP). Basically, this system is characterized by 1) an attempt to computerize as much as possible every step involved in the process of reconstitution, 2) a set of tools devised for identifying and measuring all forms and degrees of similarity between names and surnames, 3) a technique to process cases of ambiguous links, 4) a set of programs used to assess the quality of the data and the strength of the links created, and 5) an attempt to maximize the performance of the linkage work in terms of both efficiency and accuracy. The system has been designed to support several kinds of analyses, from social history and demography to population genetics. The paper contains a brief overview of the current state of research in the field record linkage, an introduction to the Saguenay population register, and a description of the system itself which has utilized sucessfully in the last year on the 660,000 Saguenay parish records, covering the period 1842-1971.

  14. A large family of Dscam genes with tandemly arrayed 5' cassettes in Chelicerata.

    PubMed

    Yue, Yuan; Meng, Yijun; Ma, Hongru; Hou, Shouqing; Cao, Guozheng; Hong, Weiling; Shi, Yang; Guo, Pengjuan; Liu, Baoping; Shi, Feng; Yang, Yun; Jin, Yongfeng

    2016-01-01

    Drosophila Dscam1 (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary isoform diversity from a single genomic locus. Dscam1 encodes 38,016 distinct isoforms via mutually exclusive splicing in D. melanogaster, while the vertebrate clustered Pcdhs utilize alternative promoters to generate isoform diversity. Here we reveal a shortened Dscam gene family with tandemly arrayed 5' cassettes in Chelicerata. These cassette repeats generally comprise two or four exons, corresponding to variable Immunoglobulin 7 (Ig7) or Ig7-8 domains of Drosophila Dscam1. Furthermore, extraordinary isoform diversity has been generated through a combination of alternating promoter and alternative splicing. These sDscams have a high sequence similarity with Drosophila Dscam1, and share striking organizational resemblance to the 5' variable regions of vertebrate clustered Pcdhs. Hence, our findings have important implications for understanding the functional similarities between Drosophila Dscam1 and vertebrate Pcdhs, and may provide further mechanistic insights into the regulation of isoform diversity. PMID:27080167

  15. 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

    Weiss, S.; Korostishevsky, M.; Frydman, M.

    1994-09-01

    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.

  16. A large plant beta-tubulin family with minimal C-terminal variation but differences in expression.

    PubMed

    Jost, Wolfgang; Baur, Armin; Nick, Peter; Reski, Ralf; Gorr, Gilbert

    2004-09-29

    Tubulins, as the major structural component of microtubules (MT), are highly conserved throughout the entire eukaryotic kingdom. They consist of alpha/beta heterodimers. Both monomers, at least in multicellular organisms, are encoded by gene families. In higher plants up to eight beta-tubulin isotypes, mostly differing in their very C-termini, have been described. These variable beta-tubulin C-termini have been discussed in the context of functional microtubule diversity. However, in plants, in contrast to vertebrates, functional isotype specificity remains yet to be demonstrated. Unlike higher plants, unicellular green algae in general do not exhibit isotypic variations. The moss Physcomitrella patens is a phylogenetic intermediate between higher plants and green algae. We isolated six beta-tubulin genes from Physcomitrella, named PpTub1 to 6. We show that the exon/intron structure, with the exception of one additional intron in PpTub6, is identical with that of higher plants, and that some members of the family are differentially expressed. Moreover, we find that all Physcomitrella isotypes are highly conserved and, most strikingly, are almost identical within their C-terminal amino acids (aa). This evolutionary ancient and large beta-tubulin gene family without significant isotypic sequence variation points to a role of differential regulation in the evolution of plant tubulin isotypes. PMID:15556303

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

    SciTech Connect

    Shashi, V.; Golden, W.L.; Allinson, P.S.

    1996-06-01

    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.

  18. Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD

    PubMed Central

    Shepard, Peter J.; Barshop, Bruce A.; Baumgartner, Matthias R.; Hansen, John-Bjarne; Jepsen, Kristen; Smith, Erin N.; Frazer, Kelly A.

    2015-01-01

    Purpose 3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD. Methods We performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases. Results We determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD. Conclusion Our study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes. PMID:25356967

  19. A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family.

    PubMed

    Saglar, Emel; Deniz, Ferhat; Erdem, Beril; Karaduman, Tugce; Yönem, Arif; Cagiltay, Eylem; Mergen, Hatice

    2014-05-01

    X-linked nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by mutations in arginine vasopressin type 2 receptor (AVPR2) and characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel 388 bp deletion starting in intron 1 and ending in exon 2 in the AVPR2 gene in a patient with NDI and in his family. We have revealed that this mutation is a de novo mutation for the mother of the proband patient. Prospective clinical data were collected for all family members. The water deprivation test confirmed the diagnosis of diabetes insipidus. The patient has severe symptoms like deep polyuria nocturia, polydipsia, and fatigue. He was given arginine vasopressin treatment while he was a child. However, he could not get well due to his nephrogenic type of illness. Both of his nephews have the same complains in addition to failure to grow. We have sequenced all exons and intron-exon boundaries of the AVPR2 gene of all family members. The analyses of bioinformatics and comparative genomics of the deletion were done via considering the DNA level damage. AVPR2 gene mutation results in the absence of the three transmembrane domains, two extracellular domains, and one cytoplasmic domain. Three-dimensional protein structure prediction was shown. We concluded that X-linked NDI and severity of illness in this family is caused by a novel 388 bp deletion in the AVPR2 gene that is predicted to truncate the receptor protein, and also this deletion may lead to dysfunctioning in protein activity and inefficient or inadequate binding abilities.

  20. Evolutionary expansion and divergence in a large family of primate-specific zinc finger transcription factor genes

    SciTech Connect

    Hamilton, A T; Huntley, S; Tran-Gyamfi, M; Baggott, D; Gordon, L; Stubbs, L

    2005-09-28

    Although most genes are conserved as one-to-one orthologs in different mammalian orders, certain gene families have evolved to comprise different numbers and types of protein-coding genes through independent series of gene duplications, divergence and gene loss in each evolutionary lineage. One such family encodes KRAB-zinc finger (KRAB-ZNF) genes, which are likely to function as transcriptional repressors. One KRAB-ZNF subfamily, the ZNF91 clade, has expanded specifically in primates to comprise more than 110 loci in the human genome, yielding large gene clusters in human chromosomes 19 and 7 and smaller clusters or isolated copies at other chromosomal locations. Although phylogenetic analysis indicates that many of these genes arose before the split between old world monkeys and new world monkeys, the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. The paralogous loci are distinguished by sequence divergence within their zinc finger arrays indicating a selection for proteins with different DNA binding specificities. RT-PCR and in situ hybridization data show that some of these ZNF genes can have tissue-specific expression patterns, however many KRAB-ZNFs that are near-ubiquitous could also be playing very specific roles in halting target pathways in all tissues except for a few, where the target is released by the absence of its repressor. The number of variant KRAB-ZNF proteins is increased not only because of the large number of loci, but also because many loci can produce multiple splice variants, which because of the modular structure of these genes may have separate and perhaps even conflicting regulatory roles. The lineage-specific duplication and rapid divergence of this family of transcription factor genes suggests a role in determining species-specific biological differences and the evolution of novel primate traits.

  1. R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family

    PubMed Central

    Korvatska, Olena; Leverenz, James B.; Jayadev, Suman; McMillan, Pamela; Kurtz, Irina; Guo, Xindi; Rumbaugh, Malia; Matsushita, Mark; Girirajan, Santhosh; Dorschner, Michael O.; Kiianitsa, Kostantin; Yu, Chang-En; Brkanac, Zoran; Garden, Gwenn A.; Raskind, Wendy H.; Bird, Thomas D.

    2016-01-01

    Importance The R47H variant in the triggering receptor expressed on myeloid cells 2 gene (TREM2), a modulator of the immune response of microglia, is a strong genetic risk factor for Alzheimer disease (AD) and possibly other neurodegenerative disorders. Objective To investigate a large family with late-onset AD (LOAD), in which R47H cosegregated with 75% of cases. Design, Setting, and Participants This study includes genetic and pathologic studies of families with LOAD from 1985 to 2014. A total of 131 families with LOAD (751 individuals) were included from the University of Washington Alzheimer Disease Research Center. To identify LOAD genes/risk factors in the LOAD123 family with 21 affected members and 12 autopsies, we sequenced 4 exomes. Candidate variants were tested for cosegregation with the disease. TREM2 R47H was genotyped in an additional 130 families with LOAD. We performed clinical and neuropathological assessments of patients with and without R47H and evaluated the variant's effect on brain pathology, cellular morphology, and expression of microglial markers. Main Outcomes and Measures We assessed the effect of TREM2 genotype on age at onset and disease duration. We compared Braak and Consortium to Establish a Registry for Alzheimer's Disease scores, presence of α-synuclein and TAR DNA-binding protein 43 aggregates, and additional vascular or Parkinson pathology in TREM2 R47H carriers vs noncarriers. Microglial activation was assessed by quantitative immunohistochemistry and morphometry. Results Twelve of 16 patients with AD in the LOAD123 family carried R47H. Eleven patients with dementia had apolipoprotein E 4 (ApoE4) and R47H genotypes. We also found a rare missense variant, D353N, in a nominated AD risk gene, unc-5 homolog C (UNC5C), in 5 affected individuals in the LOAD123 family. R47H carriers demonstrated a shortened disease duration (mean [SD], 6.7 [2.8] vs 11.1 [6.6] years; 2-tailed t test; P = .04) and more frequent α-synucleinopathy. The

  2. Lipid transfer particle from the silkworm, Bombyx mori, is a novel member of the apoB/large lipid transfer protein family[S

    PubMed Central

    Yokoyama, Hiroshi; Yokoyama, Takeru; Yuasa, Masashi; Fujimoto, Hirofumi; Sakudoh, Takashi; Honda, Naoko; Fugo, Hajime; Tsuchida, Kozo

    2013-01-01

    Lipid transfer particle (LTP) is a high-molecular-weight, very high-density lipoprotein known to catalyze the transfer of lipids between a variety of lipoproteins, including both insects and vertebrates. Studying the biosynthesis and regulation pathways of LTP in detail has not been possible due to a lack of information regarding the apoproteins. Here, we sequenced the cDNA and deduced amino acid sequences for three apoproteins of LTP from the silkworm (Bombyx mori). The three subunit proteins of the LTP are coded by two genes, apoLTP-II/I and apoLTP-III. ApoLTP-I and apoLTP-II are predicted to be generated by posttranslational cleavage of the precursor protein, apoLTP-II/I. Clusters of amphipathic secondary structure within apoLTP-II/I are similar to Homo sapiens apolipoprotein B (apoB) and insect lipophorins. The apoLTP-II/I gene is a novel member of the apoB/large lipid transfer protein gene family. ApoLTP-III has a putative conserved juvenile hormone-binding protein superfamily domain. Expression of apoLTP-II/I and apoLTP-III genes was synchronized and both genes were primarily expressed in the fat body at the stage corresponding to increased lipid transport needs. We are now in a position to study in detail the physiological role of LTP and its biosynthesis and assembly. PMID:23812557

  3. Classic Case Report of Donohue Syndrome (Leprechaunism; OMIM *246200): The Impact of Consanguineous Mating.

    PubMed

    Nijim, Yousif; Awni, Youssef; Adawi, Amin; Bowirrat, Abdalla

    2016-02-01

    Donohue syndrome ([DS]; leprechaunism) describes a genetic autosomal recessive disorder that results from the presence of homozygous or compound heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2).Donohue syndrome is associated with a fatal congenital form of dwarfism with features of intrauterine and postnatal growth retardation, exaggerated hyperglycemia with hyperinsulinism and dysmorphic abnormalities.We present a case of DS owing to the rarity of this syndrome (1 case in every million births). We discuss how the disease presents, its genetic underpinning, and its prevention.The case was encountered in an Arab male born on 1 September, 2014, for consanguineous parents. The delivery was via cesarean section at 37 weeks gestation due to severe intrauterine growth restriction and nonprogress labor term. The patient was admitted to the Neonatal Intensive Care Unit due to infection, and jaundice. Dysmorphic features, abnormalities of the craniofacial region, low birth weight, skin abnormalities, abdominal distension and hypertrichosis were observed. Laboratory examinations showed, hyperinsulinism, increased C-peptide, thrombocytopenia, leucopenia, and anemia.The diagnosis of DS was done based on the combinations of typical dysmorphic characteristics, clinical evaluation, supported by genetic analysis and exaggerated biochemical results. Genetic diagnosis of DS was performed through analysis of DNA via polymerase chain reaction (PCR). A qualitative real-time PCR was used, to monitor the amplification of a targeted DNA molecule during the PCR. Other technique using sequencing of the INSR gene, which permits genetic diagnosis, counseling, and antenatal diagnoses in subsequent pregnancies, were also performed.Treatment of DS is supportive and requires the combined efforts of a multidisciplinary team, which include pediatricians, endocrinologists, dermatologists, and other health care professionals. Currently, treatment with recombinant insulin

  4. A global assessment of a large monocot family highlights the need for group-specific analyses of invasiveness

    PubMed Central

    Moodley, Desika; Procheş, Şerban; Wilson, John R. U.

    2016-01-01

    Significant progress has been made in understanding biological invasions recently, and one of the key findings is that the determinants of naturalization and invasion success vary from group to group. Here, we explore this variation for one of the largest plant families in the world, the Araceae. This group provides an excellent opportunity for identifying determinants of invasiveness in herbaceous plants, since it is one of the families most popular with horticulturalists, with species occupying various habitats and comprising many different life forms. We first developed a checklist of 3494 species of Araceae using online databases and literature sources. We aimed to determine whether invasiveness across the introduction–naturalization–invasion continuum is associated to particular traits within the family, and whether analyses focussed on specific life forms can reveal any mechanistic correlates. Boosted regression tree models were based on species invasion statuses as the response variables, and traits associated with human use, biological characteristics and distribution as the explanatory variables. The models indicate that biological traits such as plant life form and pollinator type are consistently strong correlates of invasiveness. Additionally, large-scale correlates such as the number of native floristic regions and number of introduced regions are also influential at particular stages in the invasion continuum. We used these traits to build a phenogram showing groups defined by the similarity of characters. We identified nine groups that have a greater tendency to invasiveness (including Alocasia, the Lemnoideae and Epipremnum). From this, we propose a list of species that are not currently invasive for which we would recommend a precautionary approach to be taken. The successful management of plant invasions will depend on understanding such context-dependent effects across taxonomic groups, and across the different stages of the invasion process

  5. A global assessment of a large monocot family highlights the need for group-specific analyses of invasiveness.

    PubMed

    Moodley, Desika; Procheş, Şerban; Wilson, John R U

    2016-01-01

    Significant progress has been made in understanding biological invasions recently, and one of the key findings is that the determinants of naturalization and invasion success vary from group to group. Here, we explore this variation for one of the largest plant families in the world, the Araceae. This group provides an excellent opportunity for identifying determinants of invasiveness in herbaceous plants, since it is one of the families most popular with horticulturalists, with species occupying various habitats and comprising many different life forms. We first developed a checklist of 3494 species of Araceae using online databases and literature sources. We aimed to determine whether invasiveness across the introduction-naturalization-invasion continuum is associated to particular traits within the family, and whether analyses focussed on specific life forms can reveal any mechanistic correlates. Boosted regression tree models were based on species invasion statuses as the response variables, and traits associated with human use, biological characteristics and distribution as the explanatory variables. The models indicate that biological traits such as plant life form and pollinator type are consistently strong correlates of invasiveness. Additionally, large-scale correlates such as the number of native floristic regions and number of introduced regions are also influential at particular stages in the invasion continuum. We used these traits to build a phenogram showing groups defined by the similarity of characters. We identified nine groups that have a greater tendency to invasiveness (includingAlocasia, the Lemnoideae andEpipremnum). From this, we propose a list of species that are not currently invasive for which we would recommend a precautionary approach to be taken. The successful management of plant invasions will depend on understanding such context-dependent effects across taxonomic groups, and across the different stages of the invasion process.

  6. On the adaptive origins and maladaptive consequences of human inbreeding: parasite prevalence, immune functioning, and consanguineous marriage.

    PubMed

    Hoben, Ashley D; Buunk, Abraham P; Fincher, Corey L; Thornhill, Randy; Schaller, Mark

    2010-11-13

    We propose that consanguineous marriages arise adaptively in response to high parasite prevalence and function to maintain coadapted gene complexes and associated local adaptation that defend against local pathogens. Therefore, a greater prevalence of inbreeding by consanguineous marriage is expected in geographical regions that historically have had high levels of disease-causing parasites. Eventually such marriages may, under the contemporary high movement of people with modern transportation, jeopardize the immunity of those who practice inbreeding as this leads to an increased susceptibility to novel pathogens. Therefore, a greater frequency of inbreeding is expected to predict higher levels of contemporary mortality and morbidity from infectious diseases. This parasite model of human inbreeding was supported by an analysis involving 72 countries worldwide. We found that historically high levels of pathogen prevalence were related positively to the proportion of consanguineous marriages, and that a higher prevalence of such marriages was associated with higher contemporary mortality and morbidity due to pathogens. Our study addresses plausible alternative explanations. The results suggest that consanguineous marriage is an adaptive consequence of historical pathogen ecologies, but is maladaptive in contemporary disease ecologies.

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

    PubMed

    Alkuraya, F S

    2013-09-01

    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.

  8. Improved white spruce (Picea glauca) genome assemblies and annotation of large gene families of conifer terpenoid and phenolic defense metabolism.

    PubMed

    Warren, René L; Keeling, Christopher I; Yuen, Macaire Man Saint; Raymond, Anthony; Taylor, Greg A; Vandervalk, Benjamin P; Mohamadi, Hamid; Paulino, Daniel; Chiu, Readman; Jackman, Shaun D; Robertson, Gordon; Yang, Chen; Boyle, Brian; Hoffmann, Margarete; Weigel, Detlef; Nelson, David R; Ritland, Carol; Isabel, Nathalie; Jaquish, Barry; Yanchuk, Alvin; Bousquet, Jean; Jones, Steven J M; MacKay, John; Birol, Inanc; Bohlmann, Joerg

    2015-07-01

    White spruce (Picea glauca), a gymnosperm tree, has been established as one of the models for conifer genomics. We describe the draft genome assemblies of two white spruce genotypes, PG29 and WS77111, innovative tools for the assembly of very large genomes, and the conifer genomics resources developed in this process. The two white spruce genotypes originate from distant geographic regions of western (PG29) and eastern (WS77111) North America, and represent elite trees in two Canadian tree-breeding programs. We present an update (V3 and V4) for a previously reported PG29 V2 draft genome assembly and introduce a second white spruce genome assembly for genotype WS77111. Assemblies of the PG29 and WS77111 genomes confirm the reconstructed white spruce genome size in the 20 Gbp range, and show broad synteny. Using the PG29 V3 assembly and additional white spruce genomics and transcriptomics resources, we performed MAKER-P annotation and meticulous expert annotation of very large gene families of conifer defense metabolism, the terpene synthases and cytochrome P450s. We also comprehensively annotated the white spruce mevalonate, methylerythritol phosphate and phenylpropanoid pathways. These analyses highlighted the large extent of gene and pseudogene duplications in a conifer genome, in particular for genes of secondary (i.e. specialized) metabolism, and the potential for gain and loss of function for defense and adaptation. PMID:26017574

  9. Improved white spruce (Picea glauca) genome assemblies and annotation of large gene families of conifer terpenoid and phenolic defense metabolism.

    PubMed

    Warren, René L; Keeling, Christopher I; Yuen, Macaire Man Saint; Raymond, Anthony; Taylor, Greg A; Vandervalk, Benjamin P; Mohamadi, Hamid; Paulino, Daniel; Chiu, Readman; Jackman, Shaun D; Robertson, Gordon; Yang, Chen; Boyle, Brian; Hoffmann, Margarete; Weigel, Detlef; Nelson, David R; Ritland, Carol; Isabel, Nathalie; Jaquish, Barry; Yanchuk, Alvin; Bousquet, Jean; Jones, Steven J M; MacKay, John; Birol, Inanc; Bohlmann, Joerg

    2015-07-01

    White spruce (Picea glauca), a gymnosperm tree, has been established as one of the models for conifer genomics. We describe the draft genome assemblies of two white spruce genotypes, PG29 and WS77111, innovative tools for the assembly of very large genomes, and the conifer genomics resources developed in this process. The two white spruce genotypes originate from distant geographic regions of western (PG29) and eastern (WS77111) North America, and represent elite trees in two Canadian tree-breeding programs. We present an update (V3 and V4) for a previously reported PG29 V2 draft genome assembly and introduce a second white spruce genome assembly for genotype WS77111. Assemblies of the PG29 and WS77111 genomes confirm the reconstructed white spruce genome size in the 20 Gbp range, and show broad synteny. Using the PG29 V3 assembly and additional white spruce genomics and transcriptomics resources, we performed MAKER-P annotation and meticulous expert annotation of very large gene families of conifer defense metabolism, the terpene synthases and cytochrome P450s. We also comprehensively annotated the white spruce mevalonate, methylerythritol phosphate and phenylpropanoid pathways. These analyses highlighted the large extent of gene and pseudogene duplications in a conifer genome, in particular for genes of secondary (i.e. specialized) metabolism, and the potential for gain and loss of function for defense and adaptation.

  10. A large family of antivirulence regulators modulates the effects of transcriptional activators in Gram-negative pathogenic bacteria.

    PubMed

    Santiago, Araceli E; Ruiz-Perez, Fernando; Jo, Noah Y; Vijayakumar, Vidhya; Gong, Mei Q; Nataro, James P

    2014-05-01

    We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44-100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family. PMID:24875828

  11. A Large Family of Antivirulence Regulators Modulates the Effects of Transcriptional Activators in Gram-negative Pathogenic Bacteria

    PubMed Central

    Santiago, Araceli E.; Ruiz-Perez, Fernando; Jo, Noah Y.; Vijayakumar, Vidhya; Gong, Mei Q.; Nataro, James P.

    2014-01-01

    We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44–100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family. PMID:24875828

  12. New Family of Quantum Spin Hall Insulators in Two-dimensional Transition-Metal Halide with Large Nontrivial Band Gaps.

    PubMed

    Zhou, Liujiang; Kou, Liangzhi; Sun, Yan; Felser, Claudia; Hu, Feiming; Shan, Guangcun; Smith, Sean C; Yan, Binghai; Frauenheim, Thomas

    2015-12-01

    Topological insulators (TIs) are promising for achieving dissipationless transport devices due to the robust gapless states inside the insulating bulk gap. However, currently realized two-dimensional (2D) TIs, quantum spin Hall (QSH) insulators, suffer from ultrahigh vacuum and extremely low temperature. Thus, seeking for desirable QSH insulators with high feasibility of experimental preparation and large nontrivial gap is of great importance for wide applications in spintronics. On the basis of the first-principles calculations, we predict a novel family of 2D QSH insulators in transition-metal halide MX (M = Zr, Hf; X = Cl, Br, and I) monolayers, especially, which is the first case based on transition-metal halide-based QSH insulators. MX family has the large nontrivial gaps of 0.12-0.4 eV, comparable with bismuth (111) bilayer (0.2 eV), stanene (0.3 eV), and larger than ZrTe5 (0.1 eV) monolayers and graphene-based sandwiched heterstructures (30-70 meV). Their corresponding 3D bulk materials are weak topological insulators from stacking QSH layers, and some of bulk compounds have already been synthesized in experiment. The mechanism for 2D QSH effect in this system originates from a novel d-d band inversion, significantly different from conventional band inversion between s-p, p-p, or d-p orbitals. The realization of pure layered MX monolayers may be prepared by exfoliation from their 3D bulk phases, thus holding great promise for nanoscale device applications and stimulating further efforts on transition metal-based QSH materials.

  13. The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae.

    PubMed

    Wang, L F; Yu, M; Hansson, E; Pritchard, L I; Shiell, B; Michalski, W P; Eaton, B T

    2000-11-01

    An outbreak of acute respiratory disease in Hendra, a suburb of Brisbane, Australia, in September 1994 resulted in the deaths of 14 racing horses and a horse trainer. The causative agent was a new member of the family Paramyxoviridae. The virus was originally called Equine morbillivirus but was renamed Hendra virus (HeV) when molecular characterization highlighted differences between it and members of the genus Morbillivirus. Less than 5 years later, the closely related Nipah virus (NiV) emerged in Malaysia, spread rapidly through the pig population, and caused the deaths of over 100 people. We report the characterization of the HeV L gene and protein, the genome termini, and gene boundary sequences, thus completing the HeV genome sequence. In the highly conserved region of the L protein, the HeV sequence GDNE differs from the GDNQ found in almost all other nonsegmented negative-strand (NNS) RNA viruses. HeV has an absolutely conserved intergenic trinucleotide sequence, 3'-GAA-5', and highly conserved transcription initiation and termination sequences similar to those of respiroviruses and morbilliviruses. The large genome size (18,234 nucleotides), the unique complementary genome terminal sequences of HeV, and the limited homology with other members of the Paramyxoviridae suggest that HeV, together with NiV, should be classified in a new genus in this family. The large genome of HeV also fills a gap in the spectrum of genome sizes observed with NNS RNA virus genomes. As such, it provides a further piece in the puzzle of NNS RNA virus evolution.

  14. The Crystal Structure of Bacteriophage HK97 gp6: Defining a Large Family of Head-Tail Connector Proteins

    SciTech Connect

    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

    2010-08-17

    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 {angstrom} 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.

  15. The Crystal Structure of Bacteriophage HK97 gp6: Defining a Large Family of Head-Tail Connector Proteins

    SciTech Connect

    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

    2011-11-23

    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 Å 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.

  16. Consanguineous marriages and marriage payment: a study among three south Indian caste groups.

    PubMed

    Reddy, P G

    1988-01-01

    The present study aims at understanding the interrelations between consanguineous marriages and marriage payment. The data are collected from three castes inhabiting two regions of Nellore district, Andhra Pradesh, South India. It is evident from the study that the dowry system is more prevalent among higher castes, while the bride wealth system is more common among the lower castes in the hierarchy. Further, it can be seen that the dowry system is more prevalent in developed regions, while bride-wealth is more common in backward regions. Marriage payment is found to be less common in close kin marriages than in unrelated marriages. Most of the uncle-niece marriages are without any marriage payment, in all the castes. However, most of the matrilateral cross-cousin and patrilateral cross-cousin marriages are also without any marriage payment in the Devanga.

  17. Meckel Gruber Syndrome: Second trimester diagnosis of a case in a non-consanguineous marriage.

    PubMed

    Alam, Areej; Adhi, Mehreen; Bano, Raffat; Zubair, Aisha; Mushtaq, Ammara

    2013-01-01

    Meckel-Gruber Syndrome (MKS) is a rare, autosomal recessive genetic disorder, incompatible with life. It is characterized by enlarged polycystic kidneys and post axial polydactyly. Foetal or neonatal death is caused by pulmonary hypoplasia. We report a case of a 35 year old woman who presented at 7 weeks of gestation of her sixth pregnancy. A transabdominal anomaly ultrasound performed for her current pregnancy at 18 weeks of gestation showed features consistent with MKS. The termination of pregnancy was declined and a live newborn female was delivered via an emergency caeserean section at 34 weeks of gestation due to previous history of lower segment caesarean section (LSCS) & leaking. Physical examination of the neonate confirmed the features of MKS. The neonate died within 4-5 hours of birth. This case represented a second trimester diagnosis of a recurrent case of MKS in a non-consanguineous marriage.

  18. 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

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

    2007-01-01

    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…

  19. Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family

    PubMed Central

    de Aquino, Sibele-Nascimento; Paranaíba, Lívia-Maris-R.; Gomes, Andreia; dos-Santos-Neto, Pedro; Coletta, Ricardo-D.; Cardoso, Aline-Francoise; Frota, Ana-Cláudia; Martelli-Júnior, Hercílio

    2016-01-01

    Background The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1. Key words:Waardenburg syndrome, hearing loss, oral manifestations, mutation. PMID:27031059

  20. A Novel Member of a Zinc Transporter Family Is Defective in Acrodermatitis Enteropathica

    PubMed Central

    Wang, Kun; Zhou, Bing; Kuo, Yien-Ming; Zemansky, Jason; Gitschier, Jane

    2002-01-01

    The rare inherited condition acrodermatitis enteropathica (AE) results from a defect in the absorption of dietary zinc. Recently, we used homozygosity mapping in consanguineous Middle Eastern kindreds to localize the AE gene to an ∼3.5-cM region on 8q24. In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease. The gene encodes a histidine-rich protein, which we refer to as “hZIP4,” which is a member of a large family of transmembrane proteins, some of which are known to serve as zinc-uptake proteins. We show that Slc39A4 is abundantly expressed in mouse enterocytes and that the protein resides in the apical membrane of these cells. These findings suggest that the hZIP4 transporter is responsible for intestinal absorption of zinc. PMID:12032886

  1. A novel member of a zinc transporter family is defective in acrodermatitis enteropathica.

    PubMed

    Wang, Kun; Zhou, Bing; Kuo, Yien-Ming; Zemansky, Jason; Gitschier, Jane

    2002-07-01

    The rare inherited condition acrodermatitis enteropathica (AE) results from a defect in the absorption of dietary zinc. Recently, we used homozygosity mapping in consanguineous Middle Eastern kindreds to localize the AE gene to an approximately 3.5-cM region on 8q24. In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease. The gene encodes a histidine-rich protein, which we refer to as "hZIP4," which is a member of a large family of transmembrane proteins, some of which are known to serve as zinc-uptake proteins. We show that Slc39A4 is abundantly expressed in mouse enterocytes and that the protein resides in the apical membrane of these cells. These findings suggest that the hZIP4 transporter is responsible for intestinal absorption of zinc.

  2. High proportion of large genomic deletions and a genotype–phenotype update in 80 unrelated families with juvenile polyposis syndrome

    PubMed Central

    Aretz, S; Stienen, D; Uhlhaas, S; Stolte, M; Entius, M M; Loff, S; Back, W; Kaufmann, A; Keller, K‐M; Blaas, S H; Siebert, R; Vogt, S; Spranger, S; Holinski‐Feder, E; Sunde, L; Propping, P; Friedl, W

    2007-01-01

    Background In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. Methods Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. Results By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). Conclusions Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype‐phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted. PMID:17873119

  3. Genetic heterogeneity in Pakistani microcephaly families.

    PubMed

    Sajid Hussain, M; Marriam Bakhtiar, S; Farooq, M; Anjum, I; Janzen, E; Reza Toliat, M; Eiberg, H; Kjaer, K W; Tommerup, N; Noegel, A A; Nürnberg, P; Baig, S M; Hansen, L

    2013-05-01

    Autosomal recessive primary microcephaly (MCPH) is caused by mutations in at least eight different genes involved either in cell division or DNA repair. Most mutations are identified in consanguine families from Pakistan, Iran and India. To further assess their genetic heterogeneity and mutational spectra, we have analyzed 57 consanguine Pakistani MCPH families. In 34 MCPH families, we detected linkage to five out of the eight well-characterized disease loci and identified mutations in 27 families, leaving seven families without mutations in the coding exons of the presumably underlying MCPH genes. In the MCPH cohort 23 families could not be linked to any of the known loci, pointing to remarkable locus heterogeneity. The majority of mutations were found in ASPM followed by WDR62, CENPJ, CEP152 and MCPH1. One ASPM mutation (p.Trp1326*) was found in as many as eight families suggesting a Pakistani founder mutation. One third of the families were linked to ASPM followed by WDR62 confirming previous data. We identified three novel ASPM mutations, four novel WDR62 mutations, one novel MCPH1 mutation and two novel CEP152 mutations. CEP152 mutations have not been described before in the Pakistani population.

  4. Large repayments of premium subsidies may be owed to the IRS if family income changes are not promptly reported.

    PubMed

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

    2013-09-01

    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.

  5. Large repayments of premium subsidies may be owed to the IRS if family income changes are not promptly reported.

    PubMed

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

    2013-09-01

    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

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

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

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

    2012-06-01

    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.

  8. [Consanguineous marriage and morbi-mortality, short literature review based on an exceptional association: Usher syndrome and Von Recklinghausen neurofibromatosis].

    PubMed

    Atipo-Tsiba, Pépin-Williams

    2016-01-01

    Usher syndrome is defined by the association of a progressive or non-progressive congenital sensorineural hearing loss with variable severity and a gradually blinding pigmentary retinopathy. Von Recklinghausen neurofibromatosis or Neurofibromatosis type 1 is the major clinically form of neurofibromatosis which occurs in approximately 90% of cases. Both types of disease are genetic in origin with very low prevalence. The probability of co-occurrence of these diseases in a single individual is exceptional. Inbreeding, as well as all genetic diseases, increases quite significantly the probability of their occurrence. Consanguineous marriages are still widespread in Maghreb and in some regions of the western African. This observation reports an exceptional case of this association in a 40-year-old man of Mauritanian origin born from a consanguineous union.

  9. The Diagnostic Utility of Single Long Contiguous Stretches of Homozygosity in Patients without Parental Consanguinity

    PubMed Central

    Pajusalu, Sander; Žilina, Olga; Yakoreva, Maria; Tammur, Pille; Kuuse, Kati; Mölter-Väär, Triin; Nõukas, Margit; Reimand, Tiia; Õunap, Katrin

    2015-01-01

    We present data from our clinical department's experience with chromosomal microarray analysis (CMA) regarding the diagnostic utility of 1 or 2 long contiguous stretches of homozygosity (LCSHs) in an outbred population. The study group consisted of 2,110 consecutive patients from 2011 to 2014 for whom CMA was performed. The minimum cut-off size for defining a homozygous stretch was 5 Mb. To focus on cases with no parental consanguinity, we further studied only patients in whom the total length of homozygous stretches did not exceed 28 Mb or 1% of the autosomal genome length. We identified 6 chromosomal regions where homozygous stretches appeared in at least 3 patients and excluded these from further analysis. In 2 out of 120 patients with an isolated finding of 1 or 2 non-recurrent LCSHs, a plausible candidate gene associated with their phenotype was identified within the homozygous stretch. In both of these cases, a pathogenic mutation was detected, leading to diagnoses of pyruvate kinase deficiency and Marinesco-Sjögren syndrome. To clarify whether previously found homozygous stretches could be important for the interpretation of genome-wide sequencing data, we report 7 cases in which homozygous stretches not encompassing a clinically associated gene were first found on CMA, followed by the diagnostic whole-exome sequencing. The diagnostic utility of single LCSHs, unlikely to be caused by uniparental disomy, is discussed in detail. PMID:26733775

  10. Pattern of central nervous system anomalies in a population with a high rate of consanguineous marriages.

    PubMed

    Al-Gazali, L I; Sztriha, L; Dawodu, A; Bakir, M; Varghese, M; Varady, E; Scorer, J; Abdulrazzaq, Y M; Bener, A; Padmanabhan, R

    1999-02-01

    Nine thousand six hundred and ten births were prospectively studied in the three major hospitals in Al-Ain, United Arab Emirates (UAE) between October 1995 and January 1997. Babies suspected of, or diagnosed, as having central nervous system (CNS) abnormalities were evaluated by a neonatologist, a clinical geneticist and a pediatric neurologist. Brain computerized tomography/magnetic resonance imaging (CT/MRI) was performed on all babies suspected of having CNS abnormalities. In addition, metabolic screening and chromosome analysis were also performed when indicated. Of the 225 babies with congenital anomalies identified, 31 had CNS abnormalities (3.2/1000). Syndromic abnormalities of the CNS were present in 13 cases (42%), chromosomal abnormalities in one case (3.2%) and the rest included: neural tube defect (NTD) in 11 cases (36%), holoprosencephaly in two cases (6.4%) and hydrocephalus in four cases (12.9%). Detailed analysis of the syndromic types revealed that out of the 13 cases, 12 were inherited as autosomal recessive (AR) and in one case the inheritance was undetermined. Consanguinity with high level of inbreeding was present in 12 cases and the majority of the syndromes identified were extremely rare. The study indicates that CNS anomalies are fairly common in the UAE, particularly, the recessive syndromic types. Careful and detailed analysis of such anomalies is required so that accurate genetic advice can be given. PMID:10189086

  11. Consanguineous 3-methylcrotonyl-CoA carboxylase deficiency: early-onset necrotizing encephalopathy with lethal outcome.

    PubMed

    Baykal, T; Gokcay, G Huner; Ince, Z; Dantas, M F; Fowler, B; Baumgartner, M R; Demir, F; Can, G; Demirkol, M

    2005-01-01

    A patient with a severe neonatal variant of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is reported. The first child of healthy consanguineous Turkish parents presented on the second day of life with dehydration, cyanosis, no sucking, generalized muscular hypotonia, encephalopathy, respiratory depression requiring mechanic ventilation, macrocephaly, severe acidosis and hypoglycaemia. Elevated C5-OH-carnitine in dried blood spot by tandem MS and elevated urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine suggested MCC deficiency, confirmed by enzyme analysis in cultured fibroblasts. Cerebral ultrasonography and cranial CT findings revealed progressive changes such as disseminated encephalomalacia, cystic changes, ventricular dilatation and cerebral atrophy. Treatment with high-dose biotin and protein-restricted diet was ineffective and the patient died at the age of 33 days with progressive neurological deterioration. Mutation analysis revealed a homozygous mutation in the splice acceptor site of intron 15 in the MCC beta-subunit. Early-onset severe necrotizing encephalopathy should be included in the differential diagnosis of isolated MCC deficiency.

  12. Congenital familial subglottic stenosis: a case series and review of literature.

    PubMed

    Manickavasagam, J; Yapa, S; Bateman, N D; Thevasagayam, M S

    2014-02-01

    Subglottic stenosis is a narrowing of the endolarynx and maybe classified as congenital (primary) or acquired (secondary). Congenital stenosis maybe caused by a small cricoid cartilage, thick submucosa or other laryngeal abnormalities and remains a well-known cause of stridor in infancy. It occurs sporadically and familial occurrence is rare. Our case series identifies three children with congenital subglottic stenosis born to consanguineous parents. Congenital subglottic stenosis in siblings of unrelated parents has been previously reported, but not in consanguineous parents indicating a strong genetic link. We recommend further genetic research to assess the mode of possible heritage in this disease.

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

    SciTech Connect

    Dunne, P.W.; Doody, R.S.; Epstein, H.F.

    1994-09-01

    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.

  14. Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel

    PubMed Central

    Steiner, Hillel A.; Uradu, Andrea; Lynnes, Ty C.; Groh, William J.; Miller, John M.; Lin, Hai; Gao, Hongyu; Wang, Zhiping; Liu, Yunlong; Chen, Peng-Sheng; Vatta, Matteo

    2015-01-01

    Background The etiology of conduction disturbances necessitating permanent pacemaker (PPM) implantation is often unknown, although familial aggregation of PPM (faPPM) suggests a possible genetic basis. We developed a pan-cardiovascular next generation sequencing (NGS) panel to genetically characterize a selected cohort of faPPM. Materials and Methods We designed and validated a custom NGS panel targeting the coding and splicing regions of 246 genes with involvement in cardiac pathogenicity. We enrolled 112 PPM patients and selected nine (8%) with faPPM to be analyzed by NGS. Results Our NGS panel covers 95% of the intended target with an average of 229x read depth at a minimum of 15-fold depth, reaching a SNP true positive rate of 98%. The faPPM patients presented with isolated cardiac conduction disease (ICCD) or sick sinus syndrome (SSS) without overt structural heart disease or identifiable secondary etiology. Three patients (33.3%) had heterozygous deleterious variants previously reported in autosomal dominant cardiac diseases including CCD: LDB3 (p.D117N) and TRPM4 (p.G844D) variants in patient 4; TRPM4 (p.G844D) and ABCC9 (p.V734I) variants in patient 6; and SCN5A (p.T220I) and APOB (p.R3527Q) variants in patient 7. Conclusion FaPPM occurred in 8% of our PPM clinic population. The employment of massive parallel sequencing for a large selected panel of cardiovascular genes identified a high percentage (33.3%) of the faPPM patients with deleterious variants previously reported in autosomal dominant cardiac diseases, suggesting that genetic variants may play a role in faPPM. PMID:26636822

  15. Development and Two-Year Follow-Up Evaluation of a Training Workshop for the Large Preventive Positive Psychology Happy Family Kitchen Project in Hong Kong.

    PubMed

    Lai, Agnes Y; Mui, Moses W; Wan, Alice; Stewart, Sunita M; Yew, Carol; Lam, Tai-Hing; Chan, Sophia S

    2016-01-01

    Evidence-based practice and capacity-building approaches are essential for large-scale health promotion interventions. However, there are few models in the literature to guide and evaluate training of social service workers in community settings. This paper presents the development and evaluation of the "train-the-trainer" workshop (TTT) for the first large scale, community-based, family intervention projects, entitled "Happy Family Kitchen Project" (HFK) under the FAMILY project, a Hong Kong Jockey Club Initiative for a Harmonious Society. The workshop aimed to enhance social workers' competence and performance in applying positive psychology constructs in their family interventions under HFK to improve family well-being of the community they served. The two-day TTT was developed and implemented by a multidisciplinary team in partnership with community agencies to 50 social workers (64% women). It focused on the enhancement of knowledge, attitude, and practice of five specific positive psychology themes, which were the basis for the subsequent development of the 23 family interventions for 1419 participants. Acceptability and applicability were enhanced by completing a needs assessment prior to the training. The TTT was evaluated by trainees' reactions to the training content and design, changes in learners (trainees) and benefits to the service organizations. Focus group interviews to evaluate the workshop at three months after the training, and questionnaire survey at pre-training, immediately after, six months, one year and two years after training were conducted. There were statistically significant increases with large to moderate effect size in perceived knowledge, self-efficacy and practice after training, which sustained to 2-year follow-up. Furthermore, there were statistically significant improvements in family communication and well-being of the participants in the HFK interventions they implemented after training. This paper offers a practical example

  16. Development and Two-Year Follow-Up Evaluation of a Training Workshop for the Large Preventive Positive Psychology Happy Family Kitchen Project in Hong Kong.

    PubMed

    Lai, Agnes Y; Mui, Moses W; Wan, Alice; Stewart, Sunita M; Yew, Carol; Lam, Tai-Hing; Chan, Sophia S

    2016-01-01

    Evidence-based practice and capacity-building approaches are essential for large-scale health promotion interventions. However, there are few models in the literature to guide and evaluate training of social service workers in community settings. This paper presents the development and evaluation of the "train-the-trainer" workshop (TTT) for the first large scale, community-based, family intervention projects, entitled "Happy Family Kitchen Project" (HFK) under the FAMILY project, a Hong Kong Jockey Club Initiative for a Harmonious Society. The workshop aimed to enhance social workers' competence and performance in applying positive psychology constructs in their family interventions under HFK to improve family well-being of the community they served. The two-day TTT was developed and implemented by a multidisciplinary team in partnership with community agencies to 50 social workers (64% women). It focused on the enhancement of knowledge, attitude, and practice of five specific positive psychology themes, which were the basis for the subsequent development of the 23 family interventions for 1419 participants. Acceptability and applicability were enhanced by completing a needs assessment prior to the training. The TTT was evaluated by trainees' reactions to the training content and design, changes in learners (trainees) and benefits to the service organizations. Focus group interviews to evaluate the workshop at three months after the training, and questionnaire survey at pre-training, immediately after, six months, one year and two years after training were conducted. There were statistically significant increases with large to moderate effect size in perceived knowledge, self-efficacy and practice after training, which sustained to 2-year follow-up. Furthermore, there were statistically significant improvements in family communication and well-being of the participants in the HFK interventions they implemented after training. This paper offers a practical example

  17. Development and Two-Year Follow-Up Evaluation of a Training Workshop for the Large Preventive Positive Psychology Happy Family Kitchen Project in Hong Kong

    PubMed Central

    Lai, Agnes Y.; Mui, Moses W.; Wan, Alice; Stewart, Sunita M.; Yew, Carol; Lam, Tai-hing; Chan, Sophia S.

    2016-01-01

    Evidence-based practice and capacity-building approaches are essential for large-scale health promotion interventions. However, there are few models in the literature to guide and evaluate training of social service workers in community settings. This paper presents the development and evaluation of the “train-the-trainer” workshop (TTT) for the first large scale, community-based, family intervention projects, entitled “Happy Family Kitchen Project” (HFK) under the FAMILY project, a Hong Kong Jockey Club Initiative for a Harmonious Society. The workshop aimed to enhance social workers’ competence and performance in applying positive psychology constructs in their family interventions under HFK to improve family well-being of the community they served. The two-day TTT was developed and implemented by a multidisciplinary team in partnership with community agencies to 50 social workers (64% women). It focused on the enhancement of knowledge, attitude, and practice of five specific positive psychology themes, which were the basis for the subsequent development of the 23 family interventions for 1419 participants. Acceptability and applicability were enhanced by completing a needs assessment prior to the training. The TTT was evaluated by trainees’ reactions to the training content and design, changes in learners (trainees) and benefits to the service organizations. Focus group interviews to evaluate the workshop at three months after the training, and questionnaire survey at pre-training, immediately after, six months, one year and two years after training were conducted. There were statistically significant increases with large to moderate effect size in perceived knowledge, self-efficacy and practice after training, which sustained to 2-year follow-up. Furthermore, there were statistically significant improvements in family communication and well-being of the participants in the HFK interventions they implemented after training. This paper offers a

  18. The Politics of School Choice in Two Countries with Large Private-Dependent Sectors (Spain and Chile): Family Strategies, Collective Action and Lobbying

    ERIC Educational Resources Information Center

    Rambla, Xavier; Valiente, Oscar; Frias, Carla

    2011-01-01

    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…

  19. Familial chondrocalcinosis in the Chiloe Islands, Chile.

    PubMed Central

    Reginato, A J; Hollander, J L; Martinez, V; Valenzuela, F; Schiapachasse, V; Covarrubias, E; Jacobelli, S; Arinoviche, R; Silcox, D; Ruiz, F

    1975-01-01

    Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group. PMID:168817

  20. Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity.

    PubMed Central

    Lester, D H; Inglehearn, C F; Bashir, R; Ackford, H; Esakowitz, L; Jay, M; Bird, A C; Wright, A F; Papiha, S S; Bhattacharya, S S

    1990-01-01

    Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome. Images Figure 2 Figure 3 Figure 4 PMID:2393026

  1. Responding to the increased genetic risk associated with customary consanguineous marriage among minority ethnic populations: lessons from local innovations in England.

    PubMed

    Salway, Sarah; Ali, Parveen; Ratcliffe, Giles; Such, Elizabeth; Khan, Nasaim; Kingston, Helen; Quarrell, Oliver

    2016-07-01

    Populations practising customary consanguineous marriage have a higher incidence of autosomal recessive genetic disorders than those in which reproductive partners are usually unrelated. In the absence of any national-level response, English service developments to address the additional needs of families living with or at risk of such disorders have been locally led. These interventions remain in their infancy here, as elsewhere in Europe, and important questions remain regarding how appropriate, effective and sustainable responses can be operationalised in practice. This formative service review employed four local case studies together with wider consultation exercises over a 4-year period (2011-2015) to document recent responses to this area of need, issues arising and lessons to inform future work. Service components included the following: enhancements to genetic services to provide family-centred, culturally competent approaches to counselling and testing; community genetic literacy approaches; and capacity development among health professionals. Local approaches were, however, very varied in their detail, scope, level of investment and longevity. The provisions of culturally competent genetic counselling services and community-level genetic literacy interventions were generally well received by those who accessed them. Coordinated action across all service components appeared important for an effective service, but healthcare professionals, particularly general practitioners, were often difficult to engage in this agenda. An evaluative culture and engagement in a wider community of practice had supported service development across sites. However, sustaining investment was challenging, particularly where new services were not well integrated into core provision and where commissioning was driven by expectations of short-term reductions in infant mortality and disability.

  2. Responding to the increased genetic risk associated with customary consanguineous marriage among minority ethnic populations: lessons from local innovations in England.

    PubMed

    Salway, Sarah; Ali, Parveen; Ratcliffe, Giles; Such, Elizabeth; Khan, Nasaim; Kingston, Helen; Quarrell, Oliver

    2016-07-01

    Populations practising customary consanguineous marriage have a higher incidence of autosomal recessive genetic disorders than those in which reproductive partners are usually unrelated. In the absence of any national-level response, English service developments to address the additional needs of families living with or at risk of such disorders have been locally led. These interventions remain in their infancy here, as elsewhere in Europe, and important questions remain regarding how appropriate, effective and sustainable responses can be operationalised in practice. This formative service review employed four local case studies together with wider consultation exercises over a 4-year period (2011-2015) to document recent responses to this area of need, issues arising and lessons to inform future work. Service components included the following: enhancements to genetic services to provide family-centred, culturally competent approaches to counselling and testing; community genetic literacy approaches; and capacity development among health professionals. Local approaches were, however, very varied in their detail, scope, level of investment and longevity. The provisions of culturally competent genetic counselling services and community-level genetic literacy interventions were generally well received by those who accessed them. Coordinated action across all service components appeared important for an effective service, but healthcare professionals, particularly general practitioners, were often difficult to engage in this agenda. An evaluative culture and engagement in a wider community of practice had supported service development across sites. However, sustaining investment was challenging, particularly where new services were not well integrated into core provision and where commissioning was driven by expectations of short-term reductions in infant mortality and disability. PMID:27311843

  3. The analysis of a large Danish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 11q24.

    PubMed

    Rudkjøbing, Laura Aviaja; Eiberg, Hans; Mikkelsen, Hanne Birte; Binderup, Marie Louise Mølgaard; Bisgaard, Marie Luise

    2015-09-01

    Hereditary colorectal cancer accounts for approximately 30% of all colorectal cancers, but currently only 5% of these families can be explained by highly penetrant, inherited mutations. In the remaining 25% it is not possible to perform a gene test to identify the family members who would benefit from prophylactic screening. Consequently, all family members are asked to follow a screening program. The purpose of this study was to localize a new gene which causes colorectal cancer. We performed a linkage analysis using data from a SNP6.0 chip in one large family with 12 affected family members. We extended the linkage analysis with microsatellites (STS) and single nucleotide polymorphisms (SNP's) and looked for the loss of heterozygosity in tumour tissue. Furthermore, we performed the exome sequencing of one family member and we sequenced candidate genes by use of direct sequencing. Major rearrangements were excluded after karyotyping. The linkage analysis with SNP6 data revealed three candidate areas, on chromosome 2, 6 and 11 respectively, with a LOD score close to two and no negative LOD scores. After extended linkage analysis, the area on chromosome 6 was excluded, leaving areas on chromosome 2 and chromosome 11 with the highest possible LOD scores of 2.6. Two other studies have identified 11q24 as a candidate area for colorectal cancer susceptibility and this area is supported by our results. PMID:25724759

  4. Large genomic rearrangements in the familial breast and ovarian cancer gene BRCA1 are associated with an increased frequency of high risk features.

    PubMed

    James, Paul A; Sawyer, Sarah; Boyle, Samantha; Young, Mary-Anne; Kovalenko, Serguei; Doherty, Rebecca; McKinley, Joanne; Alsop, Kathryn; Beshay, Victoria; Harris, Marion; Fox, Stephen; Lindeman, Geoffrey J; Mitchell, Gillian

    2015-06-01

    Large genomic rearrangements (LGRs) account for at least 10% of the mutations in BRCA1 and 5% of BRCA2 mutations in outbred hereditary breast and ovarian cancer (HBOC) families. Data from some series suggest LGRs represent particularly penetrant mutations. 1,034 index cases from HBOC families underwent comprehensive BRCA1 and BRCA2 mutation testing, including screening for LGRs. The personal and family history of 254 identified mutation carriers were compared based on mutation type. Thirty-six LGRs were detected; 32/122 (26%) BRCA1 and 4/132 (3%) BRCA2 mutations. High risk features (bilateral breast cancer, diagnosis <40 years, ovarian cancer, male breast cancer) were more commonly associated with an LGR than a non-LGR mutation (p = 0.008), In families with a BRCA1 LGR the mean age of breast cancer diagnosis was younger than in families with a non-LGR BRCA1 mutation (42.5 vs. 46.1 years, p = 0.007). Across the entire group of mutation positive families the number of relatives affected by breast or ovarian cancer was increased [LGR 3.7 vs. non- LGR 2.8 per family, p value (adjusted for genotype) = 0.047]. Excluding index cases, the odds ratio for breast cancer in BRCA1 families with an LGR was 1.42 (95% CI 1.24-1.63) and for ovarian cancer 1.66 (95% CI 1.10-2.49). The increased cancer risk was reflected in significantly higher risk assessments by mutation prediction tools. LGRs are associated with higher cancer risks. If validated, LGRs could be included in cancer risk prediction tools to improve personalised cancer risk prediction estimates and may guide cost-minimising mutation screening strategies in some healthcare settings.

  5. The effect of consanguineous marriage on reading disability in the Arab community.

    PubMed

    Abu-Rabia, Salim; Maroun, Lateefeh

    2005-02-01

    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 in phonological awareness and phonological decoding than reading-disabled children of unrelated parents and normally reading younger children. These questions were investigated among 814 pupils of the 4th, 5th, and 6th grades, using word recognition and reading comprehension tests. Two experimental groups were chosen from this population. These were a reading-disabled group of 22 pupils who were children of first-cousin marriages and 21 pupils who were children of unrelated parents. A control group was also selected, consisting of 21 younger normally reading pupils at the same reading level. All the groups were tested on non-words, real words, phonological, orthographic and working memory measures. The results indicated that the rate of reading disabilities among children of first-cousin parents was higher than that of with children of second-cousin parents, distantly related parents, or unrelated parents. Further, no differences were found in phonological awareness and decoding between the two reading-disabled groups. Moreover, the results indicate a significant advantage of the younger normal readers over the reading-disabled children in the measures of phonological awareness, decoding, and orthographical knowledge that requires spelling. However, in reading common words and choosing words in context, the performance of the reading-disabled groups and the normally reading group were similar. It has been suggested that further research is needed to evaluate the role of intelligence, nevertheless our results provide new evidence for a genetic basis to reading disabilities. PMID:15747804

  6. The effect of consanguineous marriage on reading disability in the Arab community.

    PubMed

    Abu-Rabia, Salim; Maroun, Lateefeh

    2005-02-01

    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 in phonological awareness and phonological decoding than reading-disabled children of unrelated parents and normally reading younger children. These questions were investigated among 814 pupils of the 4th, 5th, and 6th grades, using word recognition and reading comprehension tests. Two experimental groups were chosen from this population. These were a reading-disabled group of 22 pupils who were children of first-cousin marriages and 21 pupils who were children of unrelated parents. A control group was also selected, consisting of 21 younger normally reading pupils at the same reading level. All the groups were tested on non-words, real words, phonological, orthographic and working memory measures. The results indicated that the rate of reading disabilities among children of first-cousin parents was higher than that of with children of second-cousin parents, distantly related parents, or unrelated parents. Further, no differences were found in phonological awareness and decoding between the two reading-disabled groups. Moreover, the results indicate a significant advantage of the younger normal readers over the reading-disabled children in the measures of phonological awareness, decoding, and orthographical knowledge that requires spelling. However, in reading common words and choosing words in context, the performance of the reading-disabled groups and the normally reading group were similar. It has been suggested that further research is needed to evaluate the role of intelligence, nevertheless our results provide new evidence for a genetic basis to reading disabilities.

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

    PubMed Central

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

    1983-01-01

    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

  8. A novel KIF11 mutation in a Turkish patient with microcephaly, lymphedema, and chorioretinal dysplasia from a consanguineous family.

    PubMed

    Hazan, Filiz; Ostergaard, Pia; Ozturk, Taylan; Kantekin, Esin; Atlihan, Fusun; Jeffery, Steve; Ozkinay, Ferda

    2012-07-01

    Microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a rare syndrome that was first described in 1992. Characteristic craniofacial features include severe microcephaly, upslanting palpebral fissures, prominent ears, a broad nose, and a long philtrum with a pointed chin. Recently, mutations in KIF11 have been demonstrated to cause dominantly inherited MLCRD syndrome. Herein, we present a patient with MLCRD syndrome whose parents were first cousins. The parents are unaffected, and thus a recessive mode of inheritance for the disorder was considered likely. However, the propositus carries a novel, de novo nonsense mutation in exon 2 of KIF11. The patient also had midline cleft tongue which has not previously been described in this syndrome.

  9. Association between Secondary and Primary Sjögren's Syndrome in a Large Collection of Lupus Families

    PubMed Central

    Aggarwal, Rachna; Anaya, Juan-Manuel; Koelsch, Kristi A.; Kurien, Biji T.; Scofield, R. Hal

    2015-01-01

    Objective. Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) share clinical and immunogenetic features and may occur together. We undertook this study to determine the risk of primary SS among SLE-unaffected relatives of SLE patients and whether or not primary and secondary SS tended to occur in the same families. Methods. We collected clinical and serological data on 2694 SLE patients, 7390 SLE-unaffected relatives of the SLE patients, and 1470 matched controls. Results. Of the 2694 subjects with SLE, 548 had secondary SS, while 71 of their 7390 SLE-unaffected relatives had primary SS. None of the 1470 controls had SS as defined herein (p = 5 × 10−5 compared to SLE-unaffected relatives). Of the 71 SLE-unaffected relatives with primary SS, 18 (25.3%) had an SLE-affected family member with secondary SS, while only 530 of the 7319 (7.2%) SLE-unaffected relatives without SS did so (p = 1 × 10−8). Conclusion. Among families identified for the presence of SLE, primary and secondary SS tend to occur within the same families. These results highlight the commonalities between these two forms of SS, which in fact correspond to the same disease. PMID:26246904

  10. The large soybean (Glycine max) WRKY TF family expanded by segmental duplication events and subsequent divergent selection among subgroups

    PubMed Central

    2013-01-01

    Background WRKY genes encode one of the most abundant groups of transcription factors in higher plants, and its members regulate important biological process such as growth, development, and responses to biotic and abiotic stresses. Although the soybean genome sequence has been published, functional studies on soybean genes still lag behind those of other species. Results We identified a total of 133 WRKY members in the soybean genome. According to structural features of their encoded proteins and to the phylogenetic tree, the soybean WRKY family could be classified into three groups (groups I, II, and III). A majority of WRKY genes (76.7%; 102 of 133) were segmentally duplicated and 13.5% (18 of 133) of the genes were tandemly duplicated. This pattern was not apparent in Arabidopsis or rice. The transcriptome atlas revealed notable differential expression in either transcript abundance or in expression patterns under normal growth conditions, which indicated wide functional divergence in this family. Furthermore, some critical amino acids were detected using DIVERGE v2.0 in specific comparisons, suggesting that these sites have contributed to functional divergence among groups or subgroups. In addition, site model and branch-site model analyses of positive Darwinian selection (PDS) showed that different selection regimes could have affected the evolution of these groups. Sites with high probabilities of having been under PDS were found in groups I, II c, II e, and III. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. Conclusions In this work, all the WRKY genes, which were generated mainly through segmental duplication, were identified in the soybean genome. Moreover, differential expression and functional divergence of the duplicated WRKY genes were two major features of this family throughout their evolutionary history. Positive selection analysis revealed that the different groups have

  11. 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

    Vyshka, Gentian; Kruja, Jera

    2013-01-01

    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. PMID:24124395

  12. Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of Patients with Autism Spectrum Disorders from a Highly Consanguineous Population.

    PubMed

    Al-Mamari, Watfa; Al-Saegh, Abeer; Al-Kindy, Adila; Bruwer, Zandre; Al-Murshedi, Fathiya; Al-Thihli, Khalid

    2015-08-01

    Autism Spectrum Disorders are a complicated group of disorders characterized with heterogeneous genetic etiologies. The genetic investigations for this group of disorders have expanded considerably over the past decade. In our study we designed a tired approach and studied the diagnostic yield of chromosomal microarray analysis on patients referred to the Genetic and Developmental Medicine clinic in Sultan Qaboos University in Oman for autism spectrum disorders in a highly consanguineous population. Copy number variants were seen in 27% of our studied cohort of patients and it was strongly associated with dysmorphic features and congenital anomalies. PMID:25703031

  13. Familial Gigantiform Cementoma

    PubMed Central

    Ma, Chunyue; Wang, Hongwei; He, Guang; Qin, Xingjun

    2016-01-01

    Abstract Familial gigantiform cementoma is an exceedingly rare but distinct subtype of cemento-osseous-fibrous lesion. Undocumented radiographic changes and related bone metabolism disorder are herein hypothesized and discussed. We present an adolescent case with recurrent familial gigantiform cementoma who received surgical intervention in our hospital. Apart from typical multiquadrant and expansile abnormalies involving both jaws, he also suffered from several times of fractures in lower extremity. Furthermore, radiographic examinations of calvaria, pelvis, femoris, tibia, and fibula all revealed radiolucent areas signifying diffuse osteopenic bone losses. Some of his consanguineous relatives bore the same burden of fractures during pubertal period. Considering these polyostotic conditions, a correlation of congenital bone metabolism disorder in cases with familial gigantiform cementoma, named “calcium steal disorder,” was thus proposed. Familial gigantiform cementoma is closely associated with “calcium steal disorder.” Whole-body dual-energy absorptiometry should be considered as a routine examination for fracture-related risk prediction. PMID:26945411

  14. Combining comparative sequence and genomic data to ascertain phylogenetic relationships and explore the evolution of the large GDSL-lipase family in land plants.

    PubMed

    Volokita, Micha; Rosilio-Brami, Tamar; Rivkin, Natalia; Zik, Moriyah

    2011-01-01

    The GDSL-lipase gene family is a very large subfamily within the supergene family of SGNH esterases, defined by the distinct GDSL amino acid motif and several highly conserved domains. Plants retain a large number of GDSL-lipases indicating that they have acquired important functions. Yet, in planta functions have been demonstrated for only a few GDSL-lipases from diverse species. Considering that orthologs often retain equivalent functions, we determined the phylogenetic relationships between GDSL-lipases from genome-sequenced species representing bryophytes, gymnosperms, monocots, and eudicots. An unrooted phylogenetic tree was constructed from the amino acid sequences of 604 GDSL-lipases from seven species. The topology of the tree depicts two major and one minor subfamily. This division is also supported by the unique gene structure of each subfamily. Because GDSL-lipase genes of all species are present in each of the three subfamilies, we conclude that the last common ancestor of the land plants already possessed at least one ancestral GDSL-lipase gene of each subfamily. Combined gene structure and synteny analyses revealed events of segmental duplications, gene transposition, and gene degeneration in the evolution of the GDSL-lipase gene family. Furthermore, these analyses showed that independent events of intron gain and loss also contributed to the extant repertoire of the GDSL-lipase gene family. Our findings suggest that underlying many of the intron losses was a spliceosomal-mediated mechanism followed by gene conversion. Sorting the phylogenetic relationships among the members of the GDSL-lipase gene family, as depicted by the tree and supported by synteny analyses, provides a framework for extrapolation of demonstrated functional data to GDSL-lipases, whose function is yet unknown. Furthermore, function(s) associated with specific lineage(s)-enriched branches may reveal correlations between acquired and/or lost functions and speciation.

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

    PubMed Central

    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

    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

  16. Consanguinity and founder effect for Gaucher disease mutation G377S in a population from Tabuleiro do Norte, Northeastern Brazil.

    PubMed

    Chaves, R G; Pereira, L da Veiga; de Araújo, F T; Rozenberg, R; Carvalho, M D F; Coelho, J C; Michelin-Tirelli, K; Chaves, M de Freitas; Cavalcanti, G B

    2015-10-01

    Gaucher's disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation. PMID:25287185

  17. Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population

    PubMed Central

    2014-01-01

    Background Genetics clearly plays a major role in the etiology of autism spectrum disorders (ASDs), but studies to date are only beginning to characterize the causal genetic variants responsible. Until recently, studies using multiple extended multi-generation families to identify ASD risk genes had not been undertaken. Methods We identified haplotypes shared among individuals with ASDs in large multiplex families, followed by targeted DNA capture and sequencing to identify potential causal variants. We also assayed the prevalence of the identified variants in a large ASD case/control population. Results We identified 584 non-conservative missense, nonsense, frameshift and splice site variants that might predispose to autism in our high-risk families. Eleven of these variants were observed to have odds ratios greater than 1.5 in a set of 1,541 unrelated children with autism and 5,785 controls. Three variants, in the RAB11FIP5, ABP1, and JMJD7-PLA2G4B genes, each were observed in a single case and not in any controls. These variants also were not seen in public sequence databases, suggesting that they may be rare causal ASD variants. Twenty-eight additional rare variants were observed only in high-risk ASD families. Collectively, these 39 variants identify 36 genes as ASD risk genes. Segregation of sequence variants and of copy number variants previously detected in these families reveals a complex pattern, with only a RAB11FIP5 variant segregating to all affected individuals in one two-generation pedigree. Some affected individuals were found to have multiple potential risk alleles, including sequence variants and copy number variants (CNVs), suggesting that the high incidence of autism in these families could be best explained by variants at multiple loci. Conclusions Our study is the first to use haplotype sharing to identify familial ASD risk loci. In total, we identified 39 variants in 36 genes that may confer a genetic risk of developing autism. The

  18. Further Evidence that Pediatric-Onset Bipolar Disorder Comorbid with ADHD Represents a Distinct Subtype: Results from a Large Controlled Family Study

    PubMed Central

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

    2012-01-01

    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

  19. Keratin-9 gene mutation in epidermolytic palmoplantar keratoderma combined with knuckle pads in a large Chinese family.

    PubMed

    Li, M; Yang, L J; Hua, H-K; Zhu, X-H; Dai, X-Y

    2009-01-01

    Epidermolytic plamoplantar keratoderma (EPPK) is an autosomal dominant inherited disease. It caused by mutations in the highly conserved coil 1A domain of the keratin 9 gene, KRT9. We studied a four-generation family with EPPK combined with knuckle pads from Jiangsu province, China. In this study, a heterozygous nucleotide T-->C transition at position 500 in exon 1 of KRT9 was detected, which resulted in a leucine to serine (L167S) change. We describe this mutation in a Chinese pedigree with EPPK with knuckle pads for the first time, demonstrating the prevalence of this mutation in diverse population.

  20. Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family

    PubMed Central

    Pathak, Anand; Seipel, Katja; Pemov, Alexander; Dewan, Ramita; Brown, Christina; Ravichandran, Sarangan; Luke, Brian T.; Malasky, Michael; Suman, Shalabh; Yeager, Meredith; Gatti, Richard A.; Caporaso, Neil E.; Mulvihill, John J.; Goldin, Lynn R.; Pabst, Thomas; McMaster, Mary L.; Stewart, Douglas R.

    2016-01-01

    Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We used whole exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mu-tant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia. PMID:26721895

  1. Topological properties of large-scale structural brain networks in children with familial risk for reading difficulties

    PubMed Central

    Hosseini, S.M. Hadi; Black, Jessica M.; Soriano, Teresa; Bugescu, Nicolle; Martinez, Rociel; Raman, Mira M.; Kesler, Shelli R.; Hoeft, Fumiko

    2013-01-01

    Developmental dyslexia is a neurobiological deficit characterized by persistent difficulty in learning to read in children and adults who otherwise possess normal intelligence. Functional and structural connectivity data suggest that developmental dyslexia could be a disconnection syndrome. However, whether abnormalities in connectivity exist in beginning readers at-risk for reading difficulties is unknown. Using graphtheoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 42 beginning readers with (FH+) and without (FH−) familial risk for reading difficulties. We constructed separate structural correlation networks based on measures of surface area and cortical thickness. Results revealed changes in topological properties in brain regions known to be abnormal in dyslexia (left supramarginal gyrus, left inferior frontal gyrus) in the FH+ group mainly in the network constructed from measures of cortical surface area. We also found alterations in topological properties in regions that are not often advertised as dyslexia but nonetheless play important role in reading (left posterior cingulate, hippocampus, and left precentral gyrus). To our knowledge, this is the first report of altered topological properties of structural correlation networks in children at risk for reading difficulty, and motivates future studies that examine the mechanisms underlying how these brain networks may mediate the influences of family history on reading outcome. PMID:23333415

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

    SciTech Connect

    Smith, S.A.; Holik, P.; Stevens, J.

    1996-01-15

    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.

  3. Functional Analysis of a Novel Connexin30 Mutation in a Large Family with Hearing Loss, Pesplanus, Ichthyosis, Cutaneous Nodules, and Keratoderma.

    PubMed

    Pandey, Nishtha; Xavier, Dennis F; Chatterjee, Arunima; Mani, Ram-Shankar; Hiremagalore, Ravi; Tharakan, Ajith; Rajashekhar, B; Anand, Anuranjan

    2016-01-01

    Mutations in the gap-junction gene Cx30 (Connexin30, GJB6) are a known cause of hearing loss. Here, we report our findings on a large multigeneration family in which severe to profound sensorineural hearing impairment is associated with a variety of skin-related anomalies. Genome-wide analysis of the family showed that the locus maps to chromosome region 13ptel-q12.1 and that a novel mutation, p.N54K, in Cx30, cosegregates with the phenotype. Unlike wild-type Cx30, p.N54K Cx30 is predominantly localized in the cytoplasm and does not permit transfer of neurobiotin, suggesting improper cellular localization and abolishment of gap-junction activity.

  4. Immunoglobulin Heavy Chain Variable Region and Major Histocompatibility Region Genes Are Linked to Induced Graves' Disease in Females From Two Very Large Families of Recombinant Inbred Mice

    PubMed Central

    Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W.; Rapoport, Basil

    2014-01-01

    Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

  5. Homozygous familial hypercholesterolemia.

    PubMed

    Alicezah, M K; Razali, R; Rahman, T; Hoh, B P; Suhana, N H; Muid, S; Nawawi, H M; Koshy, M

    2014-08-01

    We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications.

  6. Homozygous familial hypercholesterolemia.

    PubMed

    Alicezah, M K; Razali, R; Rahman, T; Hoh, B P; Suhana, N H; Muid, S; Nawawi, H M; Koshy, M

    2014-08-01

    We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications. PMID:25194536

  7. Prevalence of familial hypercholesterolemia: a meta-analysis of six large, observational, population-based studies in Poland

    PubMed Central

    Szafraniec, Krystyna; Polak, Maciej; Drygas, Wojciech; Piotrowski, Walerian; Zdrojewski, Tomasz; Jankowski, Piotr

    2016-01-01

    Introduction Familial hypercholesterolemia (FH) is a severely underdiagnosed and undertreated genetic disorder. Little is known about regional variation in the prevalence of FH, and information for Central and Eastern Europe (CEE) is scarce. This paper assesses the prevalence of FH and related cardiovascular disease (CVD) risk factors in Poland. Material and methods We performed a meta-analysis of six population-based studies in Poland. The FH was assessed using the Dutch Lipids Clinics Network (DLCN) criteria. The categories “definite” (> 8 points) and “probable” (6–8 points) were combined into “potential FH”. Combined estimates of proportions across studies were pooled by meta-analysis with a random effects model. Results A total of 37,889 persons aged 20–79 years were included in the analysis. The distribution of DLCN scores was skewed, and there were only 7 cases of definite FH. Prevalence of potential FH was 404/100,000 people (95% CI = 277–531/100,000). Familial hypercholesterolemia was more prevalent in women than in men, and the prevalence was the highest in the age group 45–54 years in men and 55–64 years in women. After adjustment for age and sex, compared to participants with normal cholesterol, persons with potential FH had twice the prevalence of hypertension (p < 0.01); smoking was more prevalent by about 80% (p < 0.01) and hypertriglyceridemia was nine times more frequent (p < 0.001). There was no difference in the prevalence of low high-density lipoprotein (HDL)-cholesterol or diabetes. Conclusions We believe that our study might facilitate the planning of a strategy to manage the disease at a population level, i.e. to develop a national strategy for the detection, diagnosis, and treatment of FH. PMID:27478447

  8. Effects of a formal training programme on consanguineous marriages on high school students' knowledge and attitudes: an interventional study from Turkey.

    PubMed

    Kisioglu, Ahmet Nesimi; Ormeci, Ahmet Rifat; Uskun, Ersin; Ozturk, Mustafa; Ongel, Kurtulus

    2010-03-01

    Consanguineous marriage is traditionally common throughout the eastern Mediterranean region. Research has suggested that it is closely linked to the sociocultural and socioeconomical status of individuals, and education plays a critical role in decreasing the number of cases. This study aimed to determine the effects of a formal training programme on consanguineous marriages on the knowledge of, and attitudes towards, consanguineous marriage of high school students (n=804) in the Mediterranean region of Turkey. Seniors from three randomly selected public high schools participated in the pre-test and post-test design study. To determine the effects of the programme, students who received the training were compared with those who did not receive any formal training about the subject. After the post-tests were administered, data were collected and analysed using chi-squared and McNemar tests. The results showed significant differences in knowledge and attitudes among the students who had received the formal training programme and those who had not. In addition, the results indicated potential peer influence between the students who received training in consanguineous marriage and those who did not.

  9. Affinal and Consanguineal Kin as a Social Support for the Rural Elderly. Paper of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, NC.

    ERIC Educational Resources Information Center

    Kivett, Vira R.

    Although the support network of elderly individuals has received increased attention recently, most research has focused on the parent child relationship without examining other levels of kin interrelations. To examine the help received by rural-transitional older adults from their consanguineous kin (adult children, grandchildren, siblings,…

  10. Mutation of HES7 in a large extended family with spondylocostal dysostosis and dextrocardia with situs inversus.

    PubMed

    Sparrow, Duncan B; Faqeih, Eissa Ali; Sallout, Bahauddin; Alswaid, Abdulrahman; Ababneh, Faroug; Al-Sayed, Moeenaldeen; Rukban, Hadeel; Eyaid, Wafaa M; Kageyama, Ryoichiro; Ellard, Sian; Turnpenny, Peter D; Dunwoodie, Sally L

    2013-09-01

    Spondylocostal dysotosis (SCD) is a rare developmental congenital abnormality of the axial skeleton. Mutation of genes in the Notch signaling pathway cause SCD types 1-5. Dextrocardia with situs inversus is a rare congenital malformation in which the thoracic and abdominal organs are mirror images of normal. Such laterality defects are associated with gene mutations in the Nodal signaling pathway or cilia assembly or function. We investigated two distantly related individuals with a rare combination of severe segmental defects of the vertebrae (SDV) and dextrocardia with situs inversus. We found that both individuals were homozygous for the same mutation in HES7, and that this mutation caused a significant reduction of HES7 protein function; HES7 mutation causes SCD4. Two other individuals with SDV from two unrelated families were found to be homozygous for the same mutation. Interestingly, although the penetrance of the vertebral defects was complete, only 3/7 had dextrocardia with situs inversus, suggesting randomization of left-right patterning. Two of the affected individuals presented with neural tube malformations including myelomeningocele, spina bifida occulta and/or Chiari II malformation. Such neural tube phenotypes are shared with the originally identified SCD4 patient, but have not been reported in the other forms of SCD. In conclusion, it appears that mutation of HES7 is uniquely associated with defects in vertebral, heart and neural tube formation, and this observation will help provide a discriminatory diagnostic guide in patients with SCD, as well as inform molecular genetic testing.

  11. MEFV alterations and population genetics analysis in a large cohort of Greek patients with familial Mediterranean fever.

    PubMed

    Giaglis, S; Papadopoulos, V; Kambas, K; Doumas, M; Tsironidou, V; Rafail, S; Kartalis, G; Speletas, M; Ritis, K

    2007-05-01

    Familial Mediterranean fever (FMF) is a disease characterized by recurrent, self-limiting bouts of fever and serositis and caused by altered pyrin due to mutated MEFV gene. FMF is common in the Mediterranean Basin populations, although with varying genetic patterns. The spectrum and clinical significance of MEFV alterations in Greece has yet not been elucidated. The aim of this study was to analyze the spectrum of MEFV alterations in FMF patients and healthy individuals in Greece. A cohort of 152 Greek FMF patients along with 140 Greek healthy controls was enrolled. Non-isotopic RNase cleavage assay (NIRCA) and sequencing allowed mutational and haplotypic analysis of the entire coding sequence of MEFV. The ARLEQUIN 2.0, DNASP 4.0 and PHYLIP software were used for population genetics analysis. Among patients, 127 (83.6%) carried at least one known mutation. The most common mutations identified were M694V (38.1%), M680I (19.7%), V726A (12.2%), E148Q (10.9%) and E230K (6.1%). The total carrier rate among healthy individuals was 0.7%. The presence of R202Q homozygosity in 12 of the remaining 25 MEFV negative FMF patients might be considered as disease related in Greeks. Population genetics analysis revealed that Greeks rely closer to the eastern rather than western populations of the Mediterranean Basin. PMID:17489852

  12. Age-standardized Incidence Rates for Leukemia Associated with Consanguineous Marriages in 68 Countries, an Ecological Study.

    PubMed

    Saadat, Mostafa

    2015-01-01

    Consanguineous marriage that defines as a union between biologically related persons has a variety of known deleterious correlations with factors that affect public health within human populations. To investigate the association between the mean of inbreeding coefficient (α) and incidence of leukemia, the present ecological study on 68 countries was carried out. Statistical analysis showed that the age-standardized incidence rate of leukemia positively correlated with log10GNI per capita (r=0.699, df=66, P<0.001) and negatively correlated with log10α (r=-0.609, df=66, P<0.001). Controlling log10GNI per capita, a significant negative correlation between log10α and the age-standardized incidence rate of leukemia was observed (r=-0.392, df=65, P=0.001). The countries were stratified according to their annual GNI per capita, low and high-income countries with GNI per capita less than and more than 10,000$, respectively. Statistical analysis showed that in high-income countries, after controlling for log10GNI per capita, the correlation between the age-standardized incidence rate of leukemia and log10α was still significant (r=-0.600, df=36, P<0.001). It should be noted that there was no significant association between the age-standardized mortality rate due to leukemia and log10α (P>0.05). The present finding indicates that the rate of leukemia, age-standardized for incidence, is lower in countries with a high prevalence of consanguineous marriages.

  13. The ATL gene family from Arabidopsis thaliana and Oryza sativa comprises a large number of putative ubiquitin ligases of the RING-H2 type.

    PubMed

    Serrano, Mario; Parra, Socorro; Alcaraz, Luis D; Guzmán, Plinio

    2006-04-01

    Ubiquitin ligases play an important regulatory role in the control of protein degradation processes via the ubiquitin/26S proteasome pathway in eukaryotes. These enzymes participate in substrate specification and mediate the transfer of ubiquitin to target proteins. A large number of ubiquitin ligases are predicted in the eukaryotes whose genomes have been sequenced; in Arabidopsis thaliana more than 1300 genes are thought to encode ubiquitin ligases. At least three classes of ubiquitin ligases are present in Arabidopsis, one of which comprises about 470 RING zinc-finger domain proteins. Within this class we have characterized the ATL family that encodes a RING-H2 finger. We identified 80 members of this family in A. thaliana and 121 in Oryza sativa. About 60% of the rice ATLs are clustered with A. thaliana ATLs, and in many cases the gene products showed sequence similarities beyond the ATL's conserved features, suggesting that they could be orthologous genes. Ninety percent of the ATLs are intronless genes, suggesting that the structure of the basic ATL protein may have evolved as a functional module. We carried out a survey of T-DNA insertions in 30% of the Arabidopsis ATL genes and screened for possible phenotypes. Four of these genes are likely to be essential for viability, since homozygous plants for the T-DNA insertion were not recovered. One of them, ATL8, is mainly expressed in young siliques, suggesting a role during embryogenesis. We also recovered a line carrying a T-DNA insertion in ATL43 that showed an ABA-insensitive phenotype, suggesting a role of this gene in the ABA response. The organization of ATLs in Arabidopsis and rice in this study will be a valuable comprehensive guide for this multigene family.

  14. A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.

    PubMed Central

    Maslen, C; Babcock, D; Raghunath, M; Steinmann, B

    1997-01-01

    Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to but genetically distinct from Marfan syndrome. Genetic-linkage analysis has implicated the fibrillin-2 gene (FBN2) as the CCA locus. Mutation analysis of two isolated CCA patients revealed missense mutations, indicating that defects in FBN2 may be responsible for this disorder. However, cosegregation of a mutant allele with the disease phenotype has not yet been established. We have investigated the primary cause of CCA in a large well-characterized kindred with five generations comprising 18 affected individuals. Previous studies demonstrated linkage of this family's CCA phenotype to FBN2. Mutation analysis of cDNA derived from the proband and her affected brother, using a nonisotopic RNase cleavage assay, revealed the partial skipping of exon 31. Approximately 25% mutant transcript is produced, which is apparently sufficient to cause a CCA phenotype. Sequence analysis of genomic DNA revealed an unusual base composition for intron 30 and identified the mutation, a g-26t transversion, in the vicinity of the splicing branch-point site in intron 30. Genomic DNA from 30 additional family members, both affected and unaffected, then was analyzed for the mutation. The results clearly demonstrate cosegregation of the branch-point mutation with the CCA phenotype. This is the first report of a CCA mutation in a multiplex family, unequivocally establishing that mutation in FBN2 are responsible for the CCA phenotype. In addition, branch-point mutations only very rarely have been associated with human disease, suggesting that the unusual composition of this intron influences splicing stability. Images Figure 2ab Figure 2c Figure 3ab Figure 3c Figure 4 Figure 6 Figure 7 PMID:9199560

  15. Homozygous carriers of APP A713T mutation in an autosomal dominant Alzheimer disease family

    PubMed Central

    Conidi, Maria E.; Bernardi, Livia; Puccio, Gianfranco; Smirne, Nicoletta; Muraca, Maria G.; Curcio, Sabrina A.M.; Colao, Rosanna; Piscopo, Paola; Gallo, Maura; Anfossi, Maria; Frangipane, Francesca; Clodomiro, Alessandra; Mirabelli, Maria; Vasso, Franca; Cupidi, Chiara; Torchia, Giusi; Di Lorenzo, Raffaele; Mandich, Paola; Confaloni, Annamaria; Maletta, Raffaele G.

    2015-01-01

    Objective: To report, for the first time, a large autosomal dominant Alzheimer disease (AD) family in which the APP A713T mutation is present in the homozygous and heterozygous state. To date, the mutation has been reported as dominant, and in the heterozygous state associated with familial AD and cerebrovascular lesions. Methods: The family described here has been genealogically reconstructed over 6 generations dating back to the 19th century. Plasma β-amyloid peptide was measured. Sequencing of causative AD genes was performed. Results: Twenty-one individuals, all but 1 born from 2 consanguineous unions, were studied: 8 were described as affected through history, 5 were studied clinically and genetically, and 8 were asymptomatic at-risk subjects. The A713T mutation was detected in the homozygous state in 3 patients and in the heterozygous state in 8 subjects (6 asymptomatic and 2 affected). Conclusions: Our findings, also supported by the β-amyloid plasma assay, confirm (1) the pathogenic role of the APP A713T mutation, (2) the specific phenotype (AD with cerebrovascular lesions) associated with this mutation, and (3) the large span of age at onset, not influenced by APOE, TOMM40, and TREM2 genes. No substantial differences concerning clinical phenotype were evidenced between heterozygous and homozygous patients, in line with the classic definition of dominance. Therefore, in this study, AD followed the classic definition of a dominant disease, contrary to that reported in a previously described AD family with recessive APP mutation. This confirms that genetic AD may be considered a disease with dominant and recessive traits of inheritance. PMID:25948718

  16. Dandy–Walker Malformation, Genitourinary Abnormalities, and Intellectual Disability in Two Families

    PubMed Central

    Gregor, Anne; Gleeson, Joseph G.; Rosti, Rasim Ozgur

    2016-01-01

    We report on two families, each with documented consanguinity and two affected with overlapping features of Dandy-Walker malformation, genitourinary abnormalities, intellectual disability, and hearing deficit. This phenotype shares similar findings with many well-known syndromes. However, the clinical findings of this syndrome categorize this as a new syndrome as compared with the phenotype of already established syndromes. Due to parental consanguinity, occurrence in siblings of both genders and the absence of manifestations in obligate carrier parents, an autosomal recessive pattern of inheritance is more likely. The authors believe that these families suggest a novel autosomal recessive cerebello–genital syndrome. Array CGH analyses of an affected did not show pathological deletions or duplications. PMID:26109232

  17. A novel transthyretin variant p.H110D (H90D) as a cause of familial amyloid polyneuropathy in a large Irish kindred.

    PubMed

    Jimenez-Zepeda, Victor H; Bahlis, Nizar J; Gilbertson, Janet; Rendell, Nigel; Porcari, Riccardo; Lachmann, Helen J; Gillmore, Julian D; Hawkins, Philip N; Rowczenio, Dorota M

    2015-03-01

    Hereditary transthyretin (ATTR) amyloidosis is caused by inheritance of an abnormal TTR gene in an autosomal dominant fashion. In its native state, TTR is a homotetramer consisting of four identical polypeptides. Mutations in the TTR gene contribute to destabilization and dissociation of the TTR tetramer, enabling abnormally folded monomers to self-assemble as amyloid fibrils. Currently, over 120 TTR variants have been described, with varying geographic distributions, degrees of amyloidogenicity and organ involvement. We report here a large Irish family with familial amyloid polyneuropathy (FAP), consisting of multiple affected generations, caused by a novel TTR mutation; p.H110D (H90D). The demonstration, by immunohistochemistry and laser micro dissection-mass spectrometry (LMD/MS) that the amyloid fibrils were composed of TTR, in conjunction with a typical FAP phenotype, indicates that the novel TTR mutation was the cause of amyloidosis. We used a molecular visualization tool PyMOL to analyze the effect of the p.H110D (H90D) replacement on the stability of the TTR molecule. Our data suggest that the loss of two hydrogen bonds and the presence of an additional negative charge in the core of a cluster of acidic residues significantly perturb the tetramer stability and likely contribute to the pathogenic role of this variant. PMID:25430583

  18. A Large Family of AvrLm6-like Genes in the Apple and Pear Scab Pathogens, Venturia inaequalis and Venturia pirina

    PubMed Central

    Shiller, Jason; Van de Wouw, Angela P.; Taranto, Adam P.; Bowen, Joanna K.; Dubois, David; Robinson, Andrew; Deng, Cecilia H.; Plummer, Kim M.

    2015-01-01

    Venturia inaequalis and V. pirina are Dothideomycete fungi that cause apple scab and pear scab disease, respectively. Whole genome sequencing of V. inaequalis and V. pirina isolates has revealed predicted proteins with sequence similarity to AvrLm6, a Leptosphaeria maculans effector that triggers a resistance response in Brassica napus and B. juncea carrying the resistance gene, Rlm6. AvrLm6-like genes are present as large families (>15 members) in all sequenced strains of V. inaequalis and V. pirina, while in L. maculans, only AvrLm6 and a single paralog have been identified. The Venturia AvrLm6-like genes are located in gene-poor regions of the genomes, and mostly in close proximity to transposable elements, which may explain the expansion of these gene families. An AvrLm6-like gene from V. inaequalis with the highest sequence identity to AvrLm6 was unable to trigger a resistance response in Rlm6-carrying B. juncea. RNA-seq and qRT-PCR gene expression analyses, of in planta- and in vitro-grown V. inaequalis, has revealed that many of the AvrLm6-like genes are expressed during infection. An AvrLm6 homolog from V. inaequalis that is up-regulated during infection was shown (using an eYFP-fusion protein construct) to be localized to the sub-cuticular stroma during biotrophic infection of apple hypocotyls. PMID:26635823

  19. Novel homozygous mutation in DSP causing skin fragility-woolly hair syndrome: report of a large family and review of the desmoplakin-related phenotypes.

    PubMed

    Al-Owain, M; Wakil, S; Shareef, F; Al-Fatani, A; Hamadah, E; Haider, M; Al-Hindi, H; Awaji, A; Khalifa, O; Baz, B; Ramadhan, R; Meyer, B

    2011-07-01

    Desmoplakin is an important cytoskeletal linker for the function of the desmosomes. Linking desmoplakin to certain types of cardiocutaneous syndromes has been a hot topic recently. Skin fragility-woolly hair syndrome is a rare autosomal recessive disorder involving the desmosomes and is caused by mutation in the desmoplakin gene (DSP). We report five members from a large family with skin fragility-woolly hair syndrome. The index is a 14-year-old girl with palmoplantar keratoderma, woolly hair, variable alopecia, dystrophic nails, and excessive blistering to trivial mechanical trauma. No cardiac symptoms were reported. Although formal cardiac examination was not feasible, the echocardiographic evaluation of the other two affected younger siblings was normal. Homozygosity mapping and linkage analysis revealed a high LOD score region in the short arm of chromosome 6 that harbors the DSP. Full sequencing of the DSP showed a novel homozygous c.7097 G>A (p.R2366H) mutation in all affected members, and the parents were heterozygous. This is the report of the third case/family of the skin fragility-woolly hair syndrome in the literature. We also present a clinical and molecular review of various desmoplakin-related phenotypes, with emphasis on onset of cardiomyopathy. The complexity of the desmoplakin and its variable presentations warrant introducing the term 'desmoplakinopathies' to describe all the phenotypes related to defects in the desmoplakin. PMID:20738328

  20. A Large Family of AvrLm6-like Genes in the Apple and Pear Scab Pathogens, Venturia inaequalis and Venturia pirina.

    PubMed

    Shiller, Jason; Van de Wouw, Angela P; Taranto, Adam P; Bowen, Joanna K; Dubois, David; Robinson, Andrew; Deng, Cecilia H; Plummer, Kim M

    2015-01-01

    Venturia inaequalis and V. pirina are Dothideomycete fungi that cause apple scab and pear scab disease, respectively. Whole genome sequencing of V. inaequalis and V. pirina isolates has revealed predicted proteins with sequence similarity to AvrLm6, a Leptosphaeria maculans effector that triggers a resistance response in Brassica napus and B. juncea carrying the resistance gene, Rlm6. AvrLm6-like genes are present as large families (>15 members) in all sequenced strains of V. inaequalis and V. pirina, while in L. maculans, only AvrLm6 and a single paralog have been identified. The Venturia AvrLm6-like genes are located in gene-poor regions of the genomes, and mostly in close proximity to transposable elements, which may explain the expansion of these gene families. An AvrLm6-like gene from V. inaequalis with the highest sequence identity to AvrLm6 was unable to trigger a resistance response in Rlm6-carrying B. juncea. RNA-seq and qRT-PCR gene expression analyses, of in planta- and in vitro-grown V. inaequalis, has revealed that many of the AvrLm6-like genes are expressed during infection. An AvrLm6 homolog from V. inaequalis that is up-regulated during infection was shown (using an eYFP-fusion protein construct) to be localized to the sub-cuticular stroma during biotrophic infection of apple hypocotyls. PMID:26635823

  1. Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

    PubMed

    Akawi, Nadia; McRae, Jeremy; Ansari, Morad; Balasubramanian, Meena; Blyth, Moira; Brady, Angela F; Clayton, Stephen; Cole, Trevor; Deshpande, Charu; Fitzgerald, Tomas W; Foulds, Nicola; Francis, Richard; Gabriel, George; Gerety, Sebastian S; Goodship, Judith; Hobson, Emma; Jones, Wendy D; Joss, Shelagh; King, Daniel; Klena, Nikolai; Kumar, Ajith; Lees, Melissa; Lelliott, Chris; Lord, Jenny; McMullan, Dominic; O'Regan, Mary; Osio, Deborah; Piombo, Virginia; Prigmore, Elena; Rajan, Diana; Rosser, Elisabeth; Sifrim, Alejandro; Smith, Audrey; Swaminathan, Ganesh J; Turnpenny, Peter; Whitworth, James; Wright, Caroline F; Firth, Helen V; Barrett, Jeffrey C; Lo, Cecilia W; FitzPatrick, David R; Hurles, Matthew E

    2015-11-01

    Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes. PMID:26437029

  2. A large inversion in the linear chromosome of Streptomyces griseus caused by replicative transposition of a new Tn3 family transposon.

    PubMed

    Murata, M; Uchida, T; Yang, Y; Lezhava, A; Kinashi, H

    2011-04-01

    We have comprehensively analyzed the linear chromosomes of Streptomyces griseus mutants constructed and kept in our laboratory. During this study, macrorestriction analysis of AseI and DraI fragments of mutant 402-2 suggested a large chromosomal inversion. The junctions of chromosomal inversion were cloned and sequenced and compared with the corresponding target sequences in the parent strain 2247. Consequently, a transposon-involved mechanism was revealed. Namely, a transposon originally located at the left target site was replicatively transposed to the right target site in an inverted direction, which generated a second copy and at the same time caused a 2.5-Mb chromosomal inversion. The involved transposon named TnSGR was grouped into a new subfamily of the resolvase-encoding Tn3 family transposons based on its gene organization. At the end, terminal diversity of S. griseus chromosomes is discussed by comparing the sequences of strains 2247 and IFO13350.

  3. Evolution of the 14-3-3 protein family: does the large number of isoforms in multicellular organisms reflect functional specificity?

    PubMed

    Rosenquist, M; Sehnke, P; Ferl, R J; Sommarin, M; Larsson, C

    2000-11-01

    14-3-3 proteins constitute a family of eukaryotic proteins that are key regulators of a large number of processes ranging from mitosis to apoptosis. 14-3-3s function as dimers and bind to particular motifs in their target proteins. To date, 14-3-3s have been implicated in regulation or stabilization of more than 35 different proteins. This number is probably only a fraction of the number of proteins that 14-3-3s bind to, as reports of new target proteins have become more frequent. An examination of 14-3-3 entries in the public databases reveals 153 isoforms, including alleloforms, reported in 48 different species. The number of isoforms range from 2, in the unicellular organism Saccharomyces cerevisiae, to 12 in the multicellular organism Arabidopsis thaliana. A phylogenetic analysis reveals that there are four major evolutionary lineages: Viridiplantae (plants), Fungi, Alveolata, and Metazoa (animals). A close examination of the aligned amino acid sequences identifies conserved amino acid residues and regions of importance for monomer stabilization, dimer formation, target protein binding, and the nuclear export function. Given the fact that 53% of the protein is conserved, including all amino acid residues in the target binding groove of the 14-3-3 monomer, one might expect little to no isoform specificity for target protein binding. However, using surface plasmon resonance we show that there are large differences in affinity between nine 14-3-3 isoforms of A. thaliana and a target peptide representing a novel binding motif present in the C terminus of the plant plasma membrane H(+)ATPase. Thus, our data suggest that one reason for the large number of isoforms found in multicellular organisms is isoform-specific functions. PMID:11080367

  4. A Single Nucleotide Variant in HNF-1β is Associated with Maturity-Onset Diabetes of the Young in a Large Chinese Family

    PubMed Central

    ZHOU, Peng; WEI, Ran; GUO, Zhenkui; ZHU, Haining; CAMPBELL, Desmond; LI, Qi; XU, Xiaoqun; WANG, Junfu; LUAN, Meng; CHEN, Xing; CHEN, Gang

    2016-01-01

    Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4α, GCK, HNF1α, IPF1, and HNF-1β, and various mutations are being reported. Methods: To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations. DNA was extracted from the periphery blood samples of (i) 9 affected members, (ii) 17 unaffected members, and (iii) 1000 healthy controls. Three pooled samples were obtained by mixing equal quantity of DNA of each individual within the each group. Totally 400 microsatellite markers across the whole genome were genotyped by capillary electrophoresis. The known MODY-related gene near the identified marker was sequenced to look for putative risk variants. Results: Allelic frequency of marker D17S798 on chromosome 17q11.2 were significantly different (P<0.001) between the affected vs. unaffected members and the affected vs. healthy controls, but not between the unaffected members vs. healthy controls. MODY5-related gene, hepatocyte nuclear factor-1β (HNF-1β) on 17q12 near D17S798 became the candidate gene. A single nucleotide variant (SNV) of C77T in the non-coding area of exon 1 of HNF-1β was found to be related to MODY5. Conclusion: This novel SNV of HNF-1β contributes to the diabetes development in the family through regulating gene expression most likely. The findings help presymptomatic diagnosis, and imply that mutations in the non-coding areas, as well as in the exons, play roles in the etiology of MODY. PMID:27114981

  5. Assessment of DPY19L2 Deletion in Familial and Non-Familial Individuals with Globozoospermia and DPY19L2 Genotyping

    PubMed Central

    Modarres, Parastoo; Tanhaei, Somayeh; Tavalaee, Marziyeh; Ghaedi, Kamran; Deemeh, Mohammad Reza; Nasr-Esfahani, Mohammad Hossein

    2016-01-01

    Background Globozoospermia is a rare syndrome with an incidence of less than 0.1% among infertile men. Researchers have recently identified a large deletion, about 200 kbp, encompassing the whole length of DPY19L2 or mutations in SPATA16 and PICK1 genes associated with globozoospermia. The aim of this study was to analyze the DPY19L2 gene deletion using polymerase chain reaction technique for the exons 1, 48, 11 and 22 as well as break point (BP) “a” in globozoospermic men. Materials and Methods In this experimental study, genome samples were collected from 27 men with globozoospermia (cases) and 36 fertile individuals (controls), and genomic analysis was carried out on each sample. Results Deletion of DPY19L2 gene accounted for 74% of individuals with globozoospermia. DPY19L2 gene deletion was considered as the molecular pathogenic factor for the onset of globozoospermia in infertile men. By quantitative real-time polymerase chain reaction (qPCR), we genotyped DPY19L2 deletion and identified carriers within the population. Conclusion This technique may be considered as a method for family counseling and has the potential to be used as a pre-implantation genetic diagnosis, especially in ethnic community with high rate of consanguineous marriages. PMID:27441053

  6. Crizotinib (PF-2341066) induces apoptosis due to downregulation of pSTAT3 and BCL-2 family proteins in NPM-ALK(+) anaplastic large cell lymphoma.

    PubMed

    Hamedani, Farid Saei; Cinar, Munevver; Mo, Zhicheng; Cervania, Melissa A; Amin, Hesham M; Alkan, Serhan

    2014-04-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is an aberrant fusion gene product with tyrosine kinase activity and is expressed in substantial subset of anaplastic large cell lymphomas (ALCL). It has been shown that NPM-ALK binds to and activates signal transducer and activator of transcription 3 (STAT3). Although NPM-ALK(+) ALCL overall shows a better prognosis, there is a sub-group of patients who relapses and is resistant to conventional chemotherapeutic regimens. NPM-ALK is a potential target for small molecule kinase inhibitors. Crizotinib (PF-2341066) is a small, orally bioavailable molecule that inhibits growth of tumors with ALK activity as shown in a subgroup of non-small lung cancer patients with EML4-ALK expression. In this study, we have investigated the in vitro effects of Crizotinib in ALCL cell line with NPM-ALK fusion. Crizotinib induced marked downregulation of STAT3 phosphorylation, which was associated with significant apoptotic cell death. Apoptosis induction was attributed to caspase-3 cleavage and marked downregulation of the Bcl-2 family of proteins including MCL-1. These findings implicate that Crizotinib has excellent potential to treat patients with NPM-ALK(+) ALCL through induction of apoptotic cell death and downregulation of major oncogenic proteins in this aggressive lymphoma.

  7. Large, larger, largest--a family of cluster-based tantalum copper aluminides with giant unit cells. II. The cluster structure.

    PubMed

    Conrad, Matthias; Harbrecht, Bernd; Weber, Thomas; Jung, Daniel Y; Steurer, Walter

    2009-06-01

    This is the second of two papers, where we discuss the cluster structures of a novel family of cluster-based intermetallic phases of unprecedented complexity: cF444-Al(63.6)Ta(36.4) (AT-19), a = 19.1663 (1) A, V = 7040 A3, cF(5928-x)-Al(56.6)Cu(3.9)Ta(39.5), x = 20 (ACT-45), a = 45.376 (1) A, V = 93,428 A3 and cF(23,256-x)-Al(55.4)Cu(5.4)Ta(39.1), x = 122 (ACT-71), a = 71.490 (4) A, V = 365,372 A3. The space group is F43m in all three cases. The structures can be described as packings of clusters such as fullerenes, dodecahedra, pentagonal bifrusta and Friauf polyhedra. A characteristic feature of the two larger structures are nets of hexagonal bipyramidal Ta clusters (h.b.p.). The extremely short distance of 2.536-2.562 A between their apical Ta atoms indicates unusually strong bonding. The large h.b.p. nets are sandwiched between slabs of Friauf polyhedra resembling the structure of the mu phase. PMID:19461141

  8. FAMILY CECIDOMYIIDAE.

    PubMed

    Maia, Valéria Cid

    2016-01-01

    This large family is poorly known in Colombia, where only 44 species have been recorded in 20 genera. All of them are included in Cecidomyiinae, which is the most diverse subfamily of gall midges in number of species and feeding habits, including phytophagous, predaceous and fungivorous species. Most of them are galler. The other subfamilies have never been recorded in this country.

  9. FAMILY CECIDOMYIIDAE.

    PubMed

    Maia, Valéria Cid

    2016-01-01

    This large family is poorly known in Colombia, where only 44 species have been recorded in 20 genera. All of them are included in Cecidomyiinae, which is the most diverse subfamily of gall midges in number of species and feeding habits, including phytophagous, predaceous and fungivorous species. Most of them are galler. The other subfamilies have never been recorded in this country. PMID:27395254

  10. Human KZNF Gene Catalog - A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors

    DOE Data Explorer

    Huntley, S; Baggott, D. M.; Hamilton, A. T.; Tran-Gyamfi, M.; Yang, S.; Kim, J.; Gordon, L.; Branscomb, E.; Stubbs, L.

    Kruppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets. [This abstract was copied from: S Huntley, DM Baggott, AT Hamilton, M Tran-Gyamfi, S Yang, J Kim, L Gordon, E Branscomb, and L Stubbs. 2006. A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors, Genome Research 16(5):669 - 677] The website provides the

  11. Consanguinity and the sib-pair method: An approach using identity by descent between and within individuals

    SciTech Connect

    Genin, E.; Clerget-Darpoux, F.

    1996-11-01

    To test for linkage between a trait and a marker, one can consider identical marker alleles in related individuals, for instance, sibs. For recessive diseases, it has been shown that some information may be gained from the identity by descent (IBD) of the two alleles of an affected inbred individual at the marker locus. The aim of this paper is to extend the sib-pair method of linkage analysis to the situation of sib pairs sampled from consanguineous populations. This extension takes maximum advantage of the information provided by both the IBD pattern between sibs and allelic identity within each sib of the pair. This is possible through the use of the condensed identity coefficients. Here, we propose a new test of linkage based on a {Chi}{sup 2}. We compare the performance of this test with that of the classical {Chi}{sup 2} test based on the distribution of sib pairs sharing 0, 1, or 2 alleles IBD. For sib pairs from first-cousin matings, the proposed test can better detect the role of a disease-susceptibility (DS) locus. Its power is shown to be greater than that of the classical test, especially for models where the DS allele may be common and incompletely penetrant; that is to say for situations that may be encountered in multifactorial diseases. A study of the impact of inbreeding on the expected proportions of sib pairs sharing 0, 1, or 2 alleles IBD is also performed here. Ignoring inbreeding, when in fact inbreeding exists, increases the rate of type I errors in tests of linkage. 21 refs., 8 figs., 9 tabs.

  12. Medical History, Lifestyle, Family History, and Occupational Risk Factors for Diffuse Large B-Cell Lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

    PubMed Central

    Kricker, Anne; Paltiel, Ora; Flowers, Christopher R.; Wang, Sophia S.; Monnereau, Alain; Blair, Aaron; Maso, Luigino Dal; Kane, Eleanor V.; Nieters, Alexandra; Foran, James M.; Miligi, Lucia; Clavel, Jacqueline; Bernstein, Leslie; Rothman, Nathaniel; Slager, Susan L.; Sampson, Joshua N.; Morton, Lindsay M.; Skibola, Christine F.

    2014-01-01

    Background Although risk factors for diffuse large B-cell lymphoma (DLBCL) have been suggested, their independent effects, modification by sex, and association with anatomical sites are largely unknown. Methods In a pooled analysis of 4667 cases and 22639 controls from 19 studies, we used stepwise logistic regression to identify the most parsimonious multivariate models for DLBCL overall, by sex, and for selected anatomical sites. Results DLBCL was associated with B-cell activating autoimmune diseases (odds ratio [OR] = 2.36, 95% confidence interval [CI] = 1.80 to 3.09), hepatitis C virus seropositivity (OR = 2.02, 95% CI = 1.47 to 2.76), family history of non-Hodgkin lymphoma (OR = 1.95, 95% CI = 1.54 to 2.47), higher young adult body mass index (OR = 1.58, 95% CI = 1.12 to 2.23, for 35+ vs 18.5 to 22.4 kg/m2), higher recreational sun exposure (OR = 0.78, 95% CI = 0.69 to 0.89), any atopic disorder (OR = 0.82, 95% CI = 0.76 to 0.89), and higher socioeconomic status (OR = 0.86, 95% CI = 0.79 to 0.94). Additional risk factors for women were occupation as field crop/vegetable farm worker (OR = 1.78, 95% CI = 1.22 to 2.60), hairdresser (OR = 1.65, 95% CI = 1.12 to 2.41), and seamstress/embroider (OR = 1.49, 95% CI = 1.13 to 1.97), low adult body mass index (OR = 0.46, 95% CI = 0.29 to 0.74, for <18.5 vs 18.5 to 22.4 kg/m2), hormone replacement therapy started age at least 50 years (OR = 0.68, 95% CI = 0.52 to 0.88), and oral contraceptive use before 1970 (OR = 0.78, 95% CI = 0.62 to 1.00); and for men were occupation as material handling equipment operator (OR = 1.58, 95% CI = 1.02 to 2.44), lifetime alcohol consumption (OR = 0.57, 95% CI = 0.44 to 0.75, for >400kg vs nondrinker), and previous blood transfusion (OR = 0.69, 95% CI = 0.57 to 0.83). Autoimmune disease, atopy, and family history of non-Hodgkin lymphoma showed similar associations across selected anatomical sites, whereas smoking was associated with central nervous system, testicular and cutaneous DLBCLs

  13. Family type and fertility: a review of literature.

    PubMed

    Kim O-k; Shah, I H

    1979-11-01

    It is generally believed that extended families encourage high fertility, but a review of the theoretical discussions and empirical research examining the relationship between family type and fertility fails to show any support for the customary belief. Nuclear families consist of husband, wife, and their immediate children. The extended family is broadly defined as any group of related persons living together which includes but is larger than the nuclear family. The main theoretical discussions of extended family and fertility are by Davis (1957); Davis and Blake (1956); Lorimer (1954); and Goode (1963; 1964). In the patrilocal extended family, the wife wants to have offspring as early as possible to strengthen the family line and her own status in the household. In a truly joint household the authority of the elders continues after marriage; the reproductive behavior of a couple is subject to their influence. Less intimate or less intense interspousal communication precludes the possibility of discussion on fertility-related problems and family planning. Younger age at marriage and lack of privacy contributes to higher fertility. According to Goode extended family behavior is characterized by more rules for behavior, while nuclear families emphasize the conjugal bond. Since most affinal and consanguineal kin are excluded from day-to-day decisions in the nuclear family there are weaker reciprocal controls.

  14. Large-scale bioinformatic analysis of the regulation of the disease resistance NBS gene family by microRNAs in Poaceae.

    PubMed

    Habachi-Houimli, Yosra; Khalfallah, Yosra; Makni, Hanem; Makni, Mohamed; Bouktila, Dhia

    2016-01-01

    In the present study, we have screened 71, 713, 525, 119 and 241 mature miRNA variants from Hordeum vulgare, Oryza sativa, Brachypodium distachyon, Triticum aestivum, and Sorghum bicolor, respectively, and classified them with respect to their conservation status and expression levels. These Poaceae non-redundant miRNA species (1,669) were distributed over a total of 625 MIR families, among which only 54 were conserved across two or more plant species, confirming the relatively recent evolutionary differentiation of miRNAs in grasses. On the other hand, we have used 257 H. vulgare, 286T. aestivum, 119 B. distachyon, 269 O. sativa, and 139 S. bicolor NBS domains, which were either mined directly from the annotated proteomes, or predicted from whole genome sequence assemblies. The hybridization potential between miRNAs and their putative NBS genes targets was analyzed, revealing that at least 454 NBS genes from all five Poaceae were potentially regulated by 265 distinct miRNA species, most of them expressed in leaves and predominantly co-expressed in additional tissues. Based on gene ontology, we could assign these probable miRNA target genes to 16 functional groups, among which three conferring resistance to bacteria (Rpm1, Xa1 and Rps2), and 13 groups of resistance to fungi (Rpp8,13, Rp3, Tsn1, Lr10, Rps1-k-1, Pm3, Rpg5, and MLA1,6,10,12,13). The results of the present analysis provide a large-scale platform for a better understanding of biological control strategies of disease resistance genes in Poaceae, and will serve as an important starting point for enhancing crop disease resistance improvement by means of transgenic lines with artificial miRNAs.

  15. Whole-exome sequencing reveals a recurrent mutation in the cathepsin C gene that causes Papillon-Lefevre syndrome in a Saudi family.

    PubMed

    Alkhiary, Yaser Mohammad; Jelani, Musharraf; Almramhi, Mona Mohammad; Mohamoud, Hussein Sheikh Ali; Al-Rehaili, Rayan; Al-Zahrani, Hams Saeed; Serafi, Rehab; Yang, Huanming; Al-Aama, Jumana Yousuf

    2016-09-01

    Papillon-Lefevre syndrome (PALS) is a rare, autosomal recessive disorder characterized by periodontitis and hyperkeratosis over the palms and soles. Mutations in the cathepsin C gene (CTSC) have been recognized as the cause of PALS since the late 1990s. More than 75 mutations in CTSC have been identified, and phenotypic variability between different mutations has been described. Next generation sequencing is widely used for efficient molecular diagnostics in various clinical practices. Here we investigated a large consanguineous Saudi family with four affected and four unaffected individuals. All of the affected individuals suffered from hyperkeratosis over the palms and soles and had anomalies of both primary and secondary dentition. For molecular diagnostics, we combined whole-exome sequencing and genome-wide homozygosity mapping procedures, and identified a recurrent homozygous missense mutation (c.899G>A; p.Gly300Asp) in exon 7 of CTSC. Validation of all eight family members by Sanger sequencing confirmed co-segregation of the pathogenic variant (c.899G>A) with the disease phenotype. This is the first report of whole-exome sequencing performed for molecular diagnosis of PALS in Saudi Arabia. Our findings provide further insights into the genotype-phenotype correlation of CTSC pathogenicity in PALS. PMID:27579005

  16. Autosomal dominant Kufs` disease: Clinical heterogeneity in nine families, and exclusion of linkage to CLN1 and CLN3 markers in a large American kindred

    SciTech Connect

    Andermann, F.; Andermann, E.; Carpenter, S.

    1994-09-01

    Most forms of neuronal ceroid lipofuscinosis (NCL) are autosomal recessive, and three genes have already been mapped: the infantile form (CLN 1); the juvenile form (CLN 3); and the early juvenile variant (CLN 5) on chromosomes 1, 16 and 13, respectively. Kufs` disease or adolescent-adult onset NCL is usually inherited as an autosomal recessive trait, and presents as three distinct clinical syndromes: progressive myoclonus epilepsy (PME) with onset in the early teens or around age 30; and onset of dementia with motor disability in the 30s. We have studied three families originating from different parts of the USA manifesting dominantly inherited Kufs` disease. Granular osmophilic deposits (GROD) were found in brain, but storage in skin was not an obligatory feature. Six dominantly inherited PME families have been ascertained from three different regions of Spain. No storage was found in skin or muscle in any of these families. The mean age of onset in the American families is earlier, the clinical manifestations more severe, and the progression much more rapid that in the Spanish families. These findings would suggest the possibility of genetic heterogeneity involving two or more loci, or different mutations at the same gene locus. Genetic linkage studies have been carried out in a six-generation New Jersey family in an attempt to characterize the gene(s) responsible for this disorder. The infantile NCL locus on chromosome 1p (CLN1) and the juvenile NCL locus on chromosome 16p (CLN 3) have been excluded in this family. Further clinical, pathological and molecular genetic studies should lead to the clarification of the diagnostic approaches in this disorder.

  17. Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: Implications for genetic testing

    PubMed Central

    Papp, Janos; Kovacs, Marietta E; Olah, Edith

    2007-01-01

    AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplification (MLPA). RESULTS: Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the definite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam I/II criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family. CONCLUSION: Our study describes for the first time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population. PMID:17569143

  18. Further Evidence for Robust Familiality of Pediatric Bipolar-I Disorder: Results from a Very Large Controlled Family Study of Pediatric Bipolar-I Disorder and a Meta-Analysis

    PubMed Central

    Wozniak, Janet; Faraone, Stephen V.; Martelon, MaryKate; McKillop, Hannah N.; Biederman, Joseph

    2013-01-01

    Objective To determine the risk for BP-I disorder in first-degree relatives of children with DSM-IV bipolar-I disorder (BP-I) via meta-analysis and expanded controlled study. Data Sources and Extraction Meta-Analysis We searched the Pubmed database for scientific articles published in the world literature in the English language through 2011. The key words searched were: bipolar disorder, first-degree relatives, family study, control. All online abstracts were reviewed and relevant full manuscripts were collected and reviewed. Citations were also examined for other potential relevant articles. We included only controlled family studies that examined rates of bipolar-I disorder in all first-degree relatives (parents and siblings) of pediatric bipolar-I probands and included only studies that had age and sex matched controls. Family history studies were excluded. Also excluded were studies that were not in English, did not report the rates of all first-degree relatives, and reported only bipolar spectrum rates. We also excluded family studies that included only adult probands. We conducted a meta-analysis of the five controlled family studies of pediatric BP-I probands that met our search criteria using the random effects model of DerSimonian and Laird. Method Family Study We greatly expanded our previous sample of DSM-IV BP-I probands using structured diagnostic interviews. Our new study included 239 children satisfying full with DSM-IV diagnostic criteria for BP-I (n=726 first-degree relatives), 162 ADHD (without BP-I) probands (n=511 first-degree relatives), and 136 healthy control (without ADHD or BP-I) probands (n=411 first-degree relatives). We used the Kaplan-Meier cumulative failure function to calculate survival curves and cumulative, lifetime risk in relatives. Cox proportional hazard models were used to calculate the risk of BP-I in relatives. Results The pooled odds ratio for BP-I disorder in relatives was estimated to be 6.96 (95% Confidence Interval (CI

  19. [Homozygous familial hypercholesterolemia].

    PubMed

    Kaylkçioğlu, Meral

    2014-10-01

    Familiar hypercholesterolemia (FH) is genetic disease characterized with extremely high levels of cholesterol leading to cholesterol deposition in skin and tissues and premature atherosclerosis due to defective LDL receptors. In homozygous individuals (HoFH) premature cardiovascular (CV) events and aortic stenosis could develop at very early ages due to the exposure of the vessels including aorta to high lipid levels since birth. Patients with HoFH do not respond to conventional antilipid agents including statins due to defective LDL receptors. Therefore,LDL apheresis is still the only choice of treatment in HoFH. However, in order to prevent both the development of CV events and aortic stenosis, regular apheresis should be initiated before the age of 10 years. With the knowledge of the 21.2% consanguineous marriages in Turkey, it could be suggested that the prevalence of FH is high in our country. However, the frequency of HoFH in Turkey is not known and there is limited data on prognosis in long term studies. This limited data denotes an extremely high mortality and morbidity in patients with HoFH. The main problem in these patients is late diagnosis leading to a delayed treatment. However, early diagnosis is the key factor for the prevention of premature atherosclerosis and for ensuring long-term survival in HoFH. Moreover, FH is a genetic disease that could be easily diagnosed with a detailed family history, physical examination, and assessment of lipid levels. In order to commence early diagnosis and early treatment, awareness of the physicians should be increased. Particularly raising the awareness among primary care physicians regarding high cholesterol levels in children and adolescents would be a substantial step. Public should realize that FH is a common disease with high mortality, and that the harms of high cholesterol begin in childhood. In order to achieve all these goals, National policy for the diagnosis and management of AH is warranted. PMID

  20. Association between familial hypercholesterolaemia and church affiliation. Is this the result of sociocultural isolation of migrant farmers in 19th-century South Africa?

    PubMed

    Torrington, M; Botha, J L; Pilcher, G J; Baker, S G

    1984-05-12

    The family trees of 57 Afrikaans -speaking familial hypercholesterolaemia (FH) index cases were traced to look for founder surnames, for an association between FH and affiliation to the Gereformeerde Kerk (GK), and for consanguinity. Two possible founder surnames were identified. Each occurred in more than 5% of individuals and both were well known among the founders of the GK. Affiliation to the GK was much more common in our sample (45% of 994 individuals) than in the general population (5%), an overall odds ratio of 7,38. This association was stronger in older generations. There were 21 consanguineous marriages, the two suspected founder surnames and affiliation to the GK featuring prominently among them. PMID:6719310

  1. 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

    Mathews, Carol A.; Grados, Marco A.

    2011-01-01

    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 TS,…

  2. The Quality of Teachers' Interactive Conversations with Preschool Children from Low-Income Families during Small-Group and Large-Group Activities

    ERIC Educational Resources Information Center

    Chen, Jennifer J.; de Groot Kim, Sonja

    2014-01-01

    This study examined the quality of preschool teachers' interactive conversations with three- and four-year-olds in two Head Start classrooms serving children from low-income families in the United States. Over a period of 20?weeks, 10 bi-weekly observations of conversations (totaling 15?h per classroom) were conducted in one small-group (Play…

  3. Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

    SciTech Connect

    Fink, J.K.; Wu, C.T.B.; Jones, S.M.

    1994-09-01

    Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North American kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.

  4. IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet–Biedl syndrome

    PubMed Central

    Aldahmesh, Mohammed A.; Li, Yuanyuan; Alhashem, Amal; Anazi, Shams; Alkuraya, Hisham; Hashem, Mais; Awaji, Ali A.; Sogaty, Sameera; Alkharashi, Abdullah; Alzahrani, Saeed; Al Hazzaa, Selwa A.; Xiong, Yong; Kong, Shanshan; Sun, Zhaoxia; Alkuraya, Fowzan S.

    2014-01-01

    Bardet–Biedl syndrome (BBS) is an autosomal recessive ciliopathy with multisystem involvement. So far, 18 BBS genes have been identified and the majority of them are essential for the function of BBSome, a protein complex involved in transporting membrane proteins into and from cilia. Yet defects in the identified genes cannot account for all the BBS cases. The genetic heterogeneity of this disease poses significant challenge to the identification of additional BBS genes. In this study, we coupled human genetics with functional validation in zebrafish and identified IFT27 as a novel BBS gene (BBS19). This is the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, highlighting the genetic complexity of this disease. PMID:24488770

  5. Identification and Clinical Implications of Novel MYO15A Mutations in a Non-consanguineous Korean Family by Targeted Exome Sequencing

    PubMed Central

    Chang, Mun Young; Kim, Ah Reum; Kim, Nayoung K.D.; Lee, Chung; Lee, Kyoung Yeul; Jeon, Woo-Sung; Koo, Ja-Won; Oh, Seung Ha; Park, Woong-Yang; Kim, Dongsup; Choi, Byung Yoon

    2015-01-01

    Mutations of MYO15A are generally known to cause severe to profound hearing loss throughout all frequencies. Here, we found two novel MYO15A mutations, c.3871C>T (p.L1291F) and c.5835T>G (p.Y1945X) in an affected individual carrying congenital profound sensorineural hearing loss (SNHL) through targeted resequencing of 134 known deafness genes. The variant, p.L1291F and p.Y1945X, resided in the myosin motor and IQ2 domains, respectively. The p.L1291F variant was predicted to affect the structure of the actin-binding site from three-dimensional protein modeling, thereby interfering with the correct interaction between actin and myosin. From the literature analysis, mutations in the N-terminal domain were more frequently associated with residual hearing at low frequencies than mutations in the other regions of this gene. Therefore we suggest a hypothetical genotype-phenotype correlation whereby MYO15A mutations that affect domains other than the N-terminal domain, lead to profound SNHL throughout all frequencies and mutations that affect the N-terminal domain, result in residual hearing at low frequencies. This genotype-phenotype correlation suggests that preservation of residual hearing during auditory rehabilitation like cochlear implantation should be intended for those who carry mutations in the N-terminal domain and that individuals with mutations elsewhere in MYO15A require early cochlear implantation to timely initiate speech development. PMID:26242193

  6. Severe mental retardation in six generations of a large South African family carrying a translocation t(6;10)(q27;q25.2).

    PubMed Central

    Brusnický, J; van Heerden, K M; de Jong, G; Cronjé, A S; Retief, A E

    1986-01-01

    Partial monosomy 10q25.2----qter, detected in a newborn baby with multiple congenital abnormalities, was found to be derived from a balanced maternal translocation t(6;10)(q27;q25.2). The pedigree of six generations of the family is presented. In an extensive cytogenetic study of this family, the chromosome complements of 57 subjects, potentially capable of carrying some form of this translocation, were analysed. A total of 14 male carriers (four obligatory) and 14 female carriers (three obligatory) of this translocation was found. Partial trisomy 10q25.2----qter, associated with severe mental retardation, occurred in nine cases, eight males and one female. Two of these eight males were detected prenatally and subsequently therapeutically aborted. The phenotypes of the family members with partial trisomy 10q25.2----qter are compared to each other and to those reported in publications. No further cases of partial monosomy 10q25.2----qter were encountered. A review of published reports of partial monosomy and partial trisomy 10qter is given. The apparent absence of infertility, the occurrence of many first trimester miscarriages, and the marked sex ratio are discussed. Images PMID:3783620

  7. FAMILY BOMBYLIIDAE.

    PubMed

    Lamas, Carlos José Einicker; Evenhuis, Neal L

    2016-01-01

    Bombyliidae is one of the largest Diptera families with more than 4,500 recognized species worldwide. Their species vary from robust to thin, and may be small to large (2-20mm) and looks like bees or wasps. They also present great variation in color. Adults can often be seen either resting and sunning themselves on trails, rocks or twigs or feeding on flowering plants as they are nectar feeders. All reared bee flies are predators or parasitoids of arthropods. The Colombian fauna of bombyliids comprises at the moment 22 species, and 12 genera, of which, six are endemic species. Nonetheless, this number may be much higher, as Colombia is a megadiverse country and there are not many specimens of this family deposited in collections all over the world. PMID:27395279

  8. Genetic linkage study of familial Mediterranean fever (FMF) to 16p13.3 and evidence for genetic heterogeneity in the Turkish population.

    PubMed

    Akarsu, A N; Saatci, U; Ozen, S; Bakkaloglu, A; Besbas, N; Sarfarazi, M

    1997-07-01

    Familial Mediterranean fever (FMF) is an autosomal recessive condition that is almost entirely restricted to the non-Askhenazi Jews, Arabs, Armenians, and Turks. Genetic linkage study of a large group of non-Turkish families has previously mapped the FMF locus to the 16p13.3 region and shown that this locus resides 0.305 cM distal to D16S246. Furthermore, allelic association has also been shown with D16S3070 (75%) and D16S3275 (66%). However, no genetic heterogeneity has been described for any of the three major reported groups of FMF families. Here, we describe the genetic linkage relationship of the fourth major group of Turkish families and report the first evidence for genetic heterogeneity of this condition. Two point linkage analysis and haplotype inspection of 15 DNA markers from the reported region of the FMF locus identified tight linkage in a group of six Turkish FMF families. A maximum lod score of 9.115 at theta = 0.00 was observed for D16S3024. Nine other DNA markers provided similar evidence of linkage with lod score values of above 5.21. However, two other FMF families were completely unlinked to this region of chromosome 16. Haplotype construction of DNA markers in five consanguineous linked families showed that a segment of homozygosity has been conserved for D16S3070 and D16S2617. No other DNA markers showed any such conservation. Therefore, we suggested that these two markers reside in close proximity to the FMF locus. Furthermore, we observed 80% allelic association with D16S2617 but no association with D16S3070 or any other DNA markers from the FMF critical region. In summary, we conclude that our Turkish families are also linked to the reported FMF locus at 16p13.3, there is a genetic heterogeneity for this condition at least in our group of Turkish families, and D16S2617 is in linkage disequilibrium in the Turkish FMF families. Combination of this study with previously published observations suggests that the FMF locus resides between D16S246

  9. A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

    PubMed

    Siddiqi, Saima; Foo, Jia Nee; Vu, Anthony; Azim, Saad; Silver, David L; Mansoor, Atika; Tay, Stacey Kiat Hong; Abbasi, Sumiya; Hashmi, Asraf Hussain; Janjua, Jamal; Khalid, Sumbal; Tai, E Shyong; Yeo, Gene W; Khor, Chiea Chuen

    2014-01-01

    The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

  10. A Novel Splice-Site Mutation in ALS2 Establishes the Diagnosis of Juvenile Amyotrophic Lateral Sclerosis in a Family with Early Onset Anarthria and Generalized Dystonias

    PubMed Central

    Vu, Anthony; Azim, Saad; Silver, David L.; Mansoor, Atika; Tay, Stacey Kiat Hong; Abbasi, Sumiya; Hashmi, Asraf Hussain; Janjua, Jamal; Khalid, Sumbal; Tai, E. Shyong; Yeo, Gene W.; Khor, Chiea Chuen

    2014-01-01

    The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes. PMID:25474699

  11. Steroid-resistant nephrotic syndrome with mutations in NPHS2 (podocin): report from a three-generation family

    PubMed Central

    Jain, Vani; Feehally, John; Jones, Gabriela; Robertson, Lisa; Nair, Dheepa; Vasudevan, Pradeep

    2014-01-01

    Genetic causes of steroid-resistant nephrotic syndrome are being increasingly recognized. Mutations in NPHS2, which encodes the glomerular protein podocin, account for up to 17% of sporadic and 40% of familial cases, where they display an autosomal-recessive pattern of inheritance. This report describes a non-consanguineous family with three generations of individuals who are either compound heterozygotes for mutations in NPHS2 or who have inherited a mutation and a non-neutral polymorphism (R229Q). As well as providing an aetiological explanation, identifying pathogenic mutations and considering genotype-phenotype correlations can provide prognostic information and lead to changes in genetic counselling and management. PMID:25852895

  12. High use of complementary and alternative medicine among a large cohort of women with a family history of breast cancer: the Sister Study.

    PubMed

    Greenlee, Heather; Sardo Molmenti, Christine L; Falci, Laura; Ulmer, Ross; Deming-Halverson, Sandra; DeRoo, Lisa A; Sandler, Dale P

    2016-04-01

    Use of complementary and alternative medicine (CAM) is high among U.S. women, yet information is limited on use among women at increased breast cancer risk. We analyzed CAM use among women with a family history of breast cancer. CAM use was analyzed among women enrolled 2003-2009 in the Sister Study cohort. Eligible women were aged 35-74, U.S. or Puerto Rican residents, no personal history of breast cancer, and had ≥1 sister with breast cancer. Baseline data on CAM use in the past year were available for 49,734 women. Logistic regression models examined the association between CAM use and Gail Model breast cancer risk score. Results were compared to female participants in the 2007 National Health Interview Survey (n = 7965). Among Sister Study participants, there was high use of vitamin/mineral supplements (79 %), mind-body practices (41 %), manipulative/body-based practices (32 %), and botanicals (23 %). Overall use was higher than the U.S. female population. No association was observed between familial breast cancer risk and CAM use. Black women were more likely to use spirituality/meditation-based CAM modalities, while non-Hispanic white and Asian women were high users of dietary supplements. In a cohort of women with increased breast cancer risk due to family history, CAM use is higher than women in the general U.S. population and is associated with race/ethnicity. Use was not associated with breast cancer risk. Given the high prevalence of CAM use among women at risk for breast caner, research on the effectiveness of CAM use for disease prevention is needed.

  13. Does Sex Moderate the Clinical Correlates of Pediatric Bipolar-I Disorder? Results from a Large Controlled Family-Genetic Study

    PubMed Central

    Wozniak, Janet; Biederman, Joseph; Martelon, MaryKate; Hernandez, Mariely; Woodworth, K. Yvonne; Faraone, Stephen V.

    2013-01-01

    Background Since little is known as to whether sex differences affect the clinical presentation of pediatric BP-I disorder, it is an area of high clinical, scientific and public health relevance. Methods Subjects are 239 BP-I probands (65 female probands, 174 male probands) and their 726 first-degree relatives, and 136 non-bipolar, non-ADHD control probands (37 female probands, 99 male probands) and their 411 first-degree relatives matched for age and sex. We modeled the psychiatric and cognitive outcomes as a function of BP-I status, sex, and the BP-I status-gender interaction. Results BP-I disorder was equally familial in both sexes. With the exception of duration of mania (shorter in females) and number of depressive episodes (more in females), there were no other meaningful differences between the sexes in clinical correlates of BP-I disorder. With the exception of a significant sex effect for panic disorder and a trend for substance use disorders (p=0.05) with female probands being at a higher risk than male probands, patterns of comorbidity were similar between the sexes. Despite the similarities, boys with BP-I disorder received more intensive and costly academic services than girls with the same disorder. Limitations Since we studied children referred to a family study of bipolar disorder, our findings may not generalize to clinic settings. Conclusions We found more similarities than differences between the sexes in the personal and familial correlates of BP-I disorder. Clinicians should consider bipolar disorder in the differential diagnosis of both boys and girls afflicted with symptoms suggestive of this disorder. PMID:23485112

  14. High use of complementary and alternative medicine among a large cohort of women with a family history of breast cancer: the Sister Study.

    PubMed

    Greenlee, Heather; Sardo Molmenti, Christine L; Falci, Laura; Ulmer, Ross; Deming-Halverson, Sandra; DeRoo, Lisa A; Sandler, Dale P

    2016-04-01

    Use of complementary and alternative medicine (CAM) is high among U.S. women, yet information is limited on use among women at increased breast cancer risk. We analyzed CAM use among women with a family history of breast cancer. CAM use was analyzed among women enrolled 2003-2009 in the Sister Study cohort. Eligible women were aged 35-74, U.S. or Puerto Rican residents, no personal history of breast cancer, and had ≥1 sister with breast cancer. Baseline data on CAM use in the past year were available for 49,734 women. Logistic regression models examined the association between CAM use and Gail Model breast cancer risk score. Results were compared to female participants in the 2007 National Health Interview Survey (n = 7965). Among Sister Study participants, there was high use of vitamin/mineral supplements (79 %), mind-body practices (41 %), manipulative/body-based practices (32 %), and botanicals (23 %). Overall use was higher than the U.S. female population. No association was observed between familial breast cancer risk and CAM use. Black women were more likely to use spirituality/meditation-based CAM modalities, while non-Hispanic white and Asian women were high users of dietary supplements. In a cohort of women with increased breast cancer risk due to family history, CAM use is higher than women in the general U.S. population and is associated with race/ethnicity. Use was not associated with breast cancer risk. Given the high prevalence of CAM use among women at risk for breast caner, research on the effectiveness of CAM use for disease prevention is needed. PMID:27017506

  15. [A family with an "Hm" phenotype transmitted over 3 generations].

    PubMed

    Salmon, C; Juszczak, G; Liberge, G; Lopez, M; Cartron, J P; Kling, C

    1978-02-01

    Hm phenotype represents a dissociation between a normal salivary expression of H substance and a very weakened expression of the antigen on red blood cells. Genetic analysis of the reported family reveals a dominant inheritance: Some members (Marie K..., Francette, Carmen) present a phenotype marked by a normal H enzyme but a deficient H antigen in erythrocyte membrane. Others Alice, Mathilde) have no expression of A1 antigen due to H substrate deficiency. H substance in salivary secretion is normal. In the other branch of this pedigree without consanguinity, Herbert presents an H substance deficiency, though quite different, as A1 antigen is expressed. In this family, Hm phenotype can be explained, without resorting to a Zm allele, by the expression of an exceptional allele at the H locus (like Am is an ABO allele). This hypothesis supports the possible polymorphism of H locus.

  16. Challenges and solutions for gene identification in the presence of familial locus heterogeneity

    PubMed Central

    Rehman, Atteeq U; Santos-Cortez, Regie Lyn P; Drummond, Meghan C; Shahzad, Mohsin; Lee, Kwanghyuk; Morell, Robert J; Ansar, Muhammad; Jan, Abid; Wang, Xin; Aziz, Abdul; Riazuddin, Saima; Smith, Joshua D; Wang, Gao T; Ahmed, Zubair M; Gul, Khitab; Shearer, A Eliot; Smith, Richard J H; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Hinnant, John; Khan, Shaheen N; Fisher, Rachel A; Ahmad, Wasim; Friderici, Karen H; Riazuddin, Sheikh; Friedman, Thomas B; Wilch, Ellen S; Leal, Suzanne M

    2015-01-01

    Next-generation sequencing (NGS) of exomes and genomes has accelerated the identification of genes involved in Mendelian phenotypes. However, many NGS studies fall short of identifying causal variants, with estimates for success rates as low as 25% for uncovering the pathological variant underlying disease etiology. An important reason for such failures is familial locus heterogeneity, where within a single pedigree causal variants in two or more genes underlie Mendelian trait etiology. As examples of intra- and inter-sibship familial locus heterogeneity, we present 10 consanguineous Pakistani families segregating hearing impairment due to homozygous variants in two different hearing impairment genes and a European-American pedigree in which hearing impairment is caused by four variants in three different genes. We have identified 41 additional pedigrees with syndromic and nonsyndromic hearing impairment for which a single previously reported hearing impairment gene has been identified but only segregates with the phenotype in a subset of affected pedigree members. We estimate that locus heterogeneity occurs in 15.3% (95% confidence interval: 11.9%, 19.9%) of the families in our collection. We demonstrate novel approaches to apply linkage analysis and homozygosity mapping (for autosomal recessive consanguineous pedigrees), which can be used to detect locus heterogeneity using either NGS or SNP array data. Results from linkage analysis and homozygosity mapping can also be used to group sibships or individuals most likely to be segregating the same causal variants and thereby increase the success rate of gene identification. PMID:25491636

  17. Truncation of the E3 ubiquitin ligase component FBXO31 causes non-syndromic autosomal recessive intellectual disability in a Pakistani family.

    PubMed

    Mir, Asif; Sritharan, Kumudesh; Mittal, Kirti; Vasli, Nasim; Araujo, Carolina; Jamil, Talal; Rafiq, Muhammad Arshad; Anwar, Zubair; Mikhailov, Anna; Rauf, Sobiah; Mahmood, Huda; Shakoor, Abdul; Ali, Sabir; So, Joyce; Naeem, Farooq; Ayub, Muhammad; Vincent, John B

    2014-08-01

    In this study, we have performed autozygosity mapping on a large consanguineous Pakistani family segregating with intellectual disability. We identified two large regions of homozygosity-by-descent (HBD) on 16q12.2-q21 and 16q24.1-q24.3. Whole exome sequencing (WES) was performed on an affected individual from the family, but initially, no obvious mutation was detected. However, three genes within the HBD regions that were not fully captured during the WES were Sanger sequenced and we identified a five base pair deletion (actually six base pairs deleted plus one base pair inserted) in exon 7 of the gene FBXO31. The variant segregated completely in the family, in recessive fashion giving a LOD score of 3.95. This variant leads to a frameshift and a premature stop codon and truncation of the FBXO31 protein, p.(Cys283Asnfs*81). Quantification of mRNA and protein expression suggests that nonsense-mediated mRNA decay also contributes to the loss of FBXO31 protein in affected individuals. FBXO31 functions as a centrosomal E3 ubiquitin ligase, in association with SKP1 and Cullin-1, involved in ubiquitination of proteins targeted for degradation. The FBXO31/SKP1/Cullin1 complex is important for neuronal morphogenesis and axonal identity. FBXO31 also plays a role in dendrite growth and neuronal migration in developing cerebellar cortex. Our finding adds further evidence of the involvement of disruption of the protein ubiquitination pathway in intellectual disability.

  18. A Novel von Hippel Lindau Gene Intronic Variant and Its Reclassification from VUS to Pathogenic: the Impact on a Large Family.

    PubMed

    Sexton, A; Rawlings, L; McKavanagh, G; Simons, K; Winship, I

    2015-12-01

    We present a case where a variant of uncertain significance in the von Hippel Lindau syndrome gene (VHL) was identified in a proband with haemangioblastoma, and in a second degree relative with phaeochromocytoma. Initial uncertainty due to the unclear nature of the variant created psychosocial challenges for this family, in which four other genetic conditions were also present. Subsequent RNA studies confirmed this as a novel pathogenic mutation affecting splicing of exon 2. A third relative has since been diagnosed with haemangioblastoma. We suggest that this mutation possibly has reduced penetrance as there was no history of haemangioblastoma, renal tumours (apart from small cysts) or other VHL tumours among five mutation positive and seven untested adult relatives at 50 % risk of the VHL mutation (average age 46 years, range 18-70 years). This case presents a novel VHL splicing mutation and highlights the psychosocial and medical value of additional laboratory studies on uncertain variants for individuals, their families and for the health professionals providing advice and counseling. PMID:26323595

  19. Familial myeloproliferative disease.

    PubMed

    Gilbert, H S

    1998-12-01

    The occurrence of one or more myeloproliferative disease (MPD) syndromes in 42 families is described. MPD appeared in a single generation in 10 families, two generations in 30 families and three generations in two families. In contrast to sparse case reports of familial polycythaemia vera, familial essential thrombocythaemia, or familial agnogenic myeloid metaplasia, in which all the involved members presented with the same MPD, 21 of the 42 families in the present series had members who presented with different MPD variants. The occurrence of multiple disease phenotypes in 'MPD families' is entirely consistent with the accepted theory of MPD as a disease arising from clonal expansion of a pluripotential haematopoietic precursor cell (PHPC) that retains its pluripotentiality and produces an array of inter-related syndromes, each named for the predominant haematic cell type involved in the proliferation. Changes in disease phenotype during the course of MPD and 'hybrid' phenotypes at the time of diagnosis are common. This report challenges the previously accepted belief that PV and other MPD variants are sporadic and randomly-occurring, and that familial occurrence of MPD is rare. The ability to identify 'MPD families' by surveying a large population of patients with MPD through the Internet, as was done in this study, and heightened awareness of familial occurrence and its phenotypic heterogeneity, should facilitate further characterization of the mode of inheritance in familial MPD and the nature of the gene mutations responsible for the dysregulation of haematopoiesis.

  20. Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry.

    PubMed

    Protasova, Maria S; Grigorenko, Anastasia P; Tyazhelova, Tatiana V; Andreeva, Tatiana V; Reshetov, Denis A; Gusev, Fedor E; Laptenko, Alexander E; Kuznetsova, Irina L; Goltsov, Andrey Y; Klyushnikov, Sergey A; Illarioshkin, Sergey N; Rogaev, Evgeny I

    2016-04-01

    X-linked congenital cerebellar ataxia is a heterogeneous nonprogressive neurodevelopmental disorder with onset in early childhood. We searched for a genetic cause of this condition, previously reported in a Buryat pedigree of Mongolian ancestry from southeastern Russia. Using whole-genome sequencing on Illumina HiSeq 2000 platform, we found a missense mutation in the ABCB7 (ABC-binding cassette transporter B7) gene, encoding a mitochondrial transporter, involved in heme synthesis and previously associated with sideroblastic anemia and ataxia. The mutation resulting in a substitution of a highly conserved glycine to serine in position 682 is apparently a major causative factor of the cerebellar hypoplasia/atrophy found in affected individuals of a Buryat family who had no evidence of sideroblastic anemia. Moreover, in these affected men we also found the genetic defects in two other genes closely linked to ABCB7 on chromosome X: a deletion of a genomic region harboring the second exon of copper-transporter gene (ATP7A) and a complete deletion of PGAM4 (phosphoglycerate mutase family member 4) retrogene located in the intronic region of the ATP7A gene. Despite the deletion, eliminating the first of six metal-binding domains in ATP7A, no signs for Menkes disease or occipital horn syndrome associated with ATP7A mutations were found in male carriers. The role of the PGAM4 gene has been previously implicated in human reproduction, but our data indicate that its complete loss does not disrupt male fertility. Our finding links cerebellar pathology to the genetic defect in ABCB7 and ATP7A structural variant inherited as X-linked trait, and further reveals the genetic heterogeneity of X-linked cerebellar disorders.

  1. A Comprehensive Catalog of Human KRAB-associated Zinc Finger Genes: Insights into the Evolutionary History of a Large Family of Transcriptional Repressors

    SciTech Connect

    Huntley, S; Baggott, D M; Hamilton, A T; Tran-Gyamfi, M; Yang, S; Kim, J; Gordon, L; Branscomb, E; Stubbs, L

    2005-09-30

    Krueppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotic species. In mammals, most ZNF proteins comprise a single class of transcriptional repressors in which a chromatin interaction domain, called the Krueppel-associated box (KRAB) is attached to a tandem array of DNA-binding zinc-finger motifs. KRAB-ZNF loci are specific to tetrapod vertebrates, but have expanded dramatically in numbers through repeated rounds of segmental duplication to create a gene family with hundreds of members in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the human genome for key motifs and used them to construct and manually curate gene models. The resulting KRAB-ZNF gene catalog includes 326 known genes, 243 of which were structurally corrected by manual annotation, and 97 novel KRAB-ZNF genes; this single family therefore comprises 20% of all predicted human transcription factor genes. Many of the genes are alternatively spliced, yielding a total of 743 distinct predicted proteins. Although many human KRAB-ZNF genes are conserved in mammals, at least 136 and potentially more than 200 genes of this type are primate-specific including many recent segmental duplicates. KRAB-ZNF genes are active in a wide variety of human tissues suggesting roles in many key biological processes, but most member genes remain completely uncharacterized. Because of their sheer numbers, wide-ranging tissue-specific expression patterns, and remarkable evolutionary divergence we predict that KRAB-ZNF transcription factors have played critical roles in crafting many aspects of human biology, including both deeply conserved and primate-specific traits.

  2. Probable autosomal recessive inheritance of polysplenia, situs inversus and cardiac defects in an Amish family.

    PubMed

    Arnold, G L; Bixler, D; Girod, D

    1983-09-01

    We report on an Amish family with five individuals in two generations with complex congenital heart disease. Autopsy findings in one and clinical examination in the others support the diagnosis of polysplenia "syndrome." In a mouse model, this spectrum of situs abnormalities and cardiovascular defects shows recessive inheritance with homozygotes having either situs solitus or situs inversus or ambiguous situs. The parents of the four affected sibs are fourth cousins. We think that the father of these four children is an affected but clinically normal homozygote, that his deceased sister was an affected homozygote, and it seems likely that they too had consanguinous parents. PMID:6638068

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

    PubMed

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

    1977-01-01

    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.

  4. Familial aggregation of Crohn’s disease and necrotizing sarcoid-like granulomatous disease

    PubMed Central

    Al-Mayouf, Sulaiman M; Albuhairan, Intisar; Muzaffer, Mohammed; AlMehaidib, Ali

    2015-01-01

    Granulomatous inflammatory diseases are disorders of an undetermined etiology, affecting different organs and having a diverse clinical course. Familial aggregation of these disorders is being reported increasingly, most commonly familial Crohn’s disease. We described the coexistence of Crohn’s disease and necrotizing sarcoid-like granulomatous disease in two siblings from a first-degree consanguineous Saudi family. The first child presented with recurrent abdominal pain associated with bloody stool and arthritis, whereas the second child presented with fever of unknown origin and lymphadenopathy as well as hepatomegaly without gastrointestinal tract disease. They are phenotypically different; however, they share a novel risk locus and allele. This report supports the heritability and familial aggregation of granulomatous inflammatory diseases and suggests that one causal mutation underlies both Crohn’s disease and necrotizing sarcoid-like granulomatous disease.

  5. [Men and family planning].

    PubMed

    Vieira, J G

    1993-01-01

    Family planning programs since their beginnings have focused exclusively on women. The importance of male participation in family planning has not been recognized. Today's society demands greater understanding and empathy between spouses, if they are to meet the new and difficult challenges of modern life. Incorporation of men into family planning programs is needed because of the deteriorating live conditions of a large segment of the population and the accelerating decomposition of social structures. Persuading men to participate in family planning should strengthen the couple and increase the probability that decisions about family size will be responsible. Strategies should be designed to interest men in family planning and increase their awareness of their role in fathering happy children who enter the world in more just and humane conditions. Such strategies must combat sex role socialization that begins in infancy. The assignment of responsibility for family planning to the woman excludes men from what should be a fundamental role.

  6. Family Meals

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Family Meals KidsHealth > For Parents > Family Meals Print A ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  7. Family Arguments

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Arguments Page Content Article Body We seem to ...

  8. Family History

    MedlinePlus

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  9. Identification of an extensive gene cluster among a family of PPOs in Trifolium pratense L. (red clover) using a large insert BAC library

    PubMed Central

    2009-01-01

    Background Polyphenol oxidase (PPO) activity in plants is a trait with potential economic, agricultural and environmental impact. In relation to the food industry, PPO-induced browning causes unacceptable discolouration in fruit and vegetables: from an agriculture perspective, PPO can protect plants against pathogens and environmental stress, improve ruminant growth by increasing nitrogen absorption and decreasing nitrogen loss to the environment through the animal's urine. The high PPO legume, red clover, has a significant economic and environmental role in sustaining low-input organic and conventional farms. Molecular markers for a range of important agricultural traits are being developed for red clover and improved knowledge of PPO genes and their structure will facilitate molecular breeding. Results A bacterial artificial chromosome (BAC) library comprising 26,016 BAC clones with an average 135 Kb insert size, was constructed from Trifolium pratense L. (red clover), a diploid legume with a haploid genome size of 440–637 Mb. Library coverage of 6–8 genome equivalents ensured good representation of genes: the library was screened for polyphenol oxidase (PPO) genes. Two single copy PPO genes, PPO4 and PPO5, were identified to add to a family of three, previously reported, paralogous genes (PPO1–PPO3). Multiple PPO1 copies were identified and characterised revealing a subfamily comprising three variants PPO1/2, PPO1/4 and PPO1/5. Six PPO genes clustered within the genome: four separate BAC clones could be assembled onto a predicted 190–510 Kb single BAC contig. Conclusion A PPO gene family in red clover resides as a cluster of at least 6 genes. Three of these genes have high homology, suggesting a more recent evolutionary event. This PPO cluster covers a longer region of the genome than clusters detected in rice or previously reported in tomato. Full-length coding sequences from PPO4, PPO5, PPO1/5 and PPO1/4 will facilitate functional studies and provide

  10. Quantitative Multiplexed Analysis of ErbB Family Co-expression for Primary Breast Cancer Prognosis in a Large Retrospective Cohort

    PubMed Central

    Giltnane, Jennifer M.; Moeder, Christopher B.; Camp, Robert L.; Rimm, David L.

    2009-01-01

    Background Assessment of outcome using a single prognostic or predictive marker is the current basis of targeted therapy, but is inherently limited by its simplicity. Multiplexing has provided better classification but only been done quantitatively using RNA or DNA. Automated quantitative analysis (AQUA) is a new technology that allows quantitative in situ assessment of protein expression. We hypothesize that multiplexed quantitative measurement of ErbB receptor family proteins may allow better prediction of outcome. Methods We quantitatively assessed the expression of six proteins in four subcellular compartments in 676 patients using breast carcinoma tissue microarrays (TMA). Then using Cox proportional hazards modeling and unsupervised hierarchical clustering, we assessed the prognostic value of the expression singly and multiplexed. Results EGFR, HER-2 and HER-3 expression were associated with decreased survival. Multivariate analysis showed high HER-2 and HER-3 expression maintained independence as prognostic markers. Hierarchical clustering of expression data defined a small class enriched for HER-2 expression with 40% 10 year survival, compared to 55% using conventional methods. Clustering also revealed a similarly poor-prognostic subgroup co-expressing EGFR and HER-3 (but low for ER, PR and HER-2) with a 42% 10 year survival. Conclusions This work shows that the combined analysis of protein expression improved prognostic classification and that multiplexed models were superior to any single marker-based method for prediction of 10-year survival. These methods illustrate a protein-based, multiplexed approach that could more accurately identify patients for targeted therapies. PMID:19330842

  11. A non-sense MCM9 mutation in a familial case of primary ovarian insufficiency.

    PubMed

    Fauchereau, F; Shalev, S; Chervinsky, E; Beck-Fruchter, R; Legois, B; Fellous, M; Caburet, S; Veitia, R A

    2016-05-01

    Primary ovarian insufficiency (POI) results in an early loss of ovarian function, and remains idiopathic in about 80% of cases. Here, we have performed a complete genetic study of a consanguineous family with two POI cases. Linkage analysis and homozygosity mapping identified 12 homozygous regions with linkage, totalling 84 Mb. Whole-exome sequencing of the two patients and a non-affected sister allowed us to detect a homozygous causal variant in the MCM9 gene. The variant c.1483G>T [p.E495*], confirmed using Sanger sequencing, introduced a premature stop codon in coding exon 8 and is expected to lead to the loss of a functional protein. MCM9 belongs to a complex required for DNA repair by homologous recombination, and its impairment in mouse is known to induce meiotic recombination defects and oocyte degeneration. A previous study recently described two consanguineous families in which homozygous mutations of MCM9 were responsible for POI and short stature. Interestingly, the affected sisters in the family described here had a normal height. Altogether, our results provide the confirmation of the implication of MCM9 variants in POI and expand their phenotypic spectrum. PMID:26771056

  12. Exome sequencing identifies ATP4A gene as responsible of an atypical familial type I gastric neuroendocrine tumour.

    PubMed

    Calvete, Oriol; Reyes, Jose; Zuñiga, Sheila; Paumard-Hernández, Beatriz; Fernández, Victoria; Bujanda, Luís; Rodriguez-Pinilla, María S; Palacios, Jose; Heine-Suñer, Damian; Banka, Siddharth; Newman, William G; Cañamero, Marta; Pritchard, D Mark; Benítez, Javier

    2015-05-15

    Gastric neuroendocrine tumours (NETs) arise from enterochromaffin-like cells, which are located in oxyntic glands within the stomach. Type I tumours represent 70-80% of gastric NETs and are associated with hypergastrinaemia, chronic atrophic gastritis and achlorhydria. Gastrin is involved in the endocrine regulation of gastric acid production. Most type I gastric NETs are sporadic, have a good prognosis and their genetic basis are unknown. We performed an exome sequencing study in a family with consanguineous parents and 10 children, five of whom were affected by type I gastric NET. Atypical clinical traits included an earlier age of onset (around 30 years), aggressiveness (three had nodal infiltration requiring total gastrectomy and one an adenocarcinoma) and iron-deficiency rather than megaloblastic anaemia. We identified a homozygous missense mutation in the 14th exon of the ATP4A gene (c.2107C>T), which encodes the proton pump responsible for acid secretion by gastric parietal cells. The amino acid p.Arg703Cys is highly conserved across species and originates a change of one of the transmembrane domains that avoids the liberation of protons from cells to stomach. This is consistent with the achlorhydria that was observed in the affected individuals. No germline or somatic mutations in the ATP4A gene were found in sporadic gastric NET patients. Based on the results of this large family, it seems that this atypical form of gastric NET has an earlier age of onset, behaves more aggressively and has atypical clinical traits that differentiated from other studied cases. PMID:25678551

  13. Families in the Military

    MedlinePlus

    ... have led to deployment of large numbers of military personnel (active duty, Reserves, National Guard). As a result ... worries and plans for the future. Let your child know that the family member is making a ...

  14. Deep RNA-Seq profile reveals biodiversity, plant-microbe interactions and a large family of NBS-LRR resistance genes in walnut (Juglans regia) tissues.

    PubMed

    Chakraborty, Sandeep; Britton, Monica; Martínez-García, P J; Dandekar, Abhaya M

    2016-03-01

    Deep RNA-Seq profiling, a revolutionary method used for quantifying transcriptional levels, often includes non-specific transcripts from other co-existing organisms in spite of stringent protocols. Using the recently published walnut genome sequence as a filter, we present a broad analysis of the RNA-Seq derived transcriptome profiles obtained from twenty different tissues to extract the biodiversity and possible plant-microbe interactions in the walnut ecosystem in California. Since the residual nature of the transcripts being analyzed does not provide sufficient information to identify the exact strain, inferences made are constrained to the genus level. The presence of the pathogenic oomycete Phytophthora was detected in the root through the presence of a glyceraldehyde-3-phosphate dehydrogenase. Cryptococcus, the causal agent of cryptococcosis, was found in the catkins and vegetative buds, corroborating previous work indicating that the plant surface supported the sexual cycle of this human pathogen. The RNA-Seq profile revealed several species of the endophytic nitrogen fixing Actinobacteria. Another bacterial species implicated in aerobic biodegradation of methyl tert-butyl ether (Methylibium petroleiphilum) is also found in the root. RNA encoding proteins from the pea aphid were found in the leaves and vegetative buds, while a serine protease from mosquito with significant homology to a female reproductive tract protease from Drosophila mojavensis in the vegetative bud suggests egg-laying activities. The comprehensive analysis of RNA-seq data present also unraveled detailed, tissue-specific information of ~400 transcripts encoded by the largest family of resistance (R) genes (NBS-LRR), which possibly rationalizes the resistance of the specific walnut plant to the pathogens detected. Thus, we elucidate the biodiversity and possible plant-microbe interactions in several walnut (Juglans regia) tissues in California using deep RNA-Seq profiling.

  15. Obsessive–compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs

    PubMed Central

    den Braber, A; Zilhão, N R; Fedko, I O; Hottenga, J-J; Pool, R; Smit, D J A; Cath, D C; Boomsma, D I

    2016-01-01

    Variation in obsessive–compulsive symptoms (OCS) has a heritable basis, with genetic association studies starting to yield the first suggestive findings. We contribute to insights into the genetic basis of OCS by performing an extensive series of genetic analyses in a homogeneous, population-based sample from the Netherlands. First, phenotypic and genetic longitudinal correlations over a 6-year period were estimated by modeling OCS data from twins and siblings. Second, polygenic risk scores (PRS) for 6931 subjects with genotype and OCS data were calculated based on meta-analysis results from IOCDF-GC, to investigate their predictive value. Third, the contribution of measured single nucleotide polymorphisms (SNPs) to the heritability was estimated using random-effects modeling. Last, we performed an exploratory genome-wide association study (GWAS) of OCS, testing for SNP- and for gene-based associations. Stability in OCS (test–retest correlation 0.63) was mainly explained by genetic stability. The PRS based on clinical samples predicted OCS in our population-based twin-family sample. SNP-based heritability was estimated at 14%. GWAS revealed one SNP (rs8100480), located within the MEF2BNB gene, associated with OCS (P=2.56 × 10−8). Additional gene-based testing resulted in four significantly associated genes, which are located in the same chromosomal region on chromosome 19p13.11: MEF2BNB, RFXANK, MEF2BNB-MEF2B and MEF2B. Thus, common genetic variants explained a significant proportion of OCS trait variation. Genes significantly associated with OCS are expressed in the brain and involved in development and control of immune system functions (RFXANK) and regulation of gene expression of muscle-specific genes (MEF2BNB). MEF2BNB also showed a suggestive association with OCD in an independent case–control study, suggesting a role for this gene in the development of OCS. PMID:26859814

  16. Obsessive-compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs.

    PubMed

    den Braber, A; Zilhão, N R; Fedko, I O; Hottenga, J-J; Pool, R; Smit, D J A; Cath, D C; Boomsma, D I

    2016-01-01

    Variation in obsessive-compulsive symptoms (OCS) has a heritable basis, with genetic association studies starting to yield the first suggestive findings. We contribute to insights into the genetic basis of OCS by performing an extensive series of genetic analyses in a homogeneous, population-based sample from the Netherlands. First, phenotypic and genetic longitudinal correlations over a 6-year period were estimated by modeling OCS data from twins and siblings. Second, polygenic risk scores (PRS) for 6931 subjects with genotype and OCS data were calculated based on meta-analysis results from IOCDF-GC, to investigate their predictive value. Third, the contribution of measured single nucleotide polymorphisms (SNPs) to the heritability was estimated using random-effects modeling. Last, we performed an exploratory genome-wide association study (GWAS) of OCS, testing for SNP- and for gene-based associations. Stability in OCS (test-retest correlation 0.63) was mainly explained by genetic stability. The PRS based on clinical samples predicted OCS in our population-based twin-family sample. SNP-based heritability was estimated at 14%. GWAS revealed one SNP (rs8100480), located within the MEF2BNB gene, associated with OCS (P=2.56 × 10(-8)). Additional gene-based testing resulted in four significantly associated genes, which are located in the same chromosomal region on chromosome 19p13.11: MEF2BNB, RFXANK, MEF2BNB-MEF2B and MEF2B. Thus, common genetic variants explained a significant proportion of OCS trait variation. Genes significantly associated with OCS are expressed in the brain and involved in development and control of immune system functions (RFXANK) and regulation of gene expression of muscle-specific genes (MEF2BNB). MEF2BNB also showed a suggestive association with OCD in an independent case-control study, suggesting a role for this gene in the development of OCS. PMID:26859814

  17. Sugar beet contains a large CONSTANS-LIKE gene family including a CO homologue that is independent of the early-bolting (B) gene locus

    PubMed Central

    Chia, T. Y. P.; Müller, A.; Jung, C.; Mutasa-Göttgens, E. S.

    2008-01-01

    Floral transition in the obligate long-day (LD) plant sugar beet (Beta vulgaris ssp. vulgaris) is tightly linked to the B gene, a dominant early-bolting quantitative trait locus, the expression of which is positively regulated by LD photoperiod. Thus, photoperiod regulators like CONSTANS (CO) and CONSTANS-LIKE (COL) genes identified in many LD and short-day (SD)-responsive plants have long been considered constituents and/or candidates for the B gene. Until now, the photoperiod response pathway of sugar beet (a Caryophyllid), diverged from the Rosids and Asterids has not been identified. Here, evidence supporting the existence of a COL gene family is provided and the presence of Group I, II, and III COL genes in sugar beet, as characterized by different zinc-finger (B-box) and CCT (CO, CO-like, TOC) domains is demonstrated. BvCOL1 is identified as a close-homologue of Group 1a (AtCO, AtCOL1, AtCOL2) COL genes, hence a good candidate for flowering time control and it is shown that it maps to chromosome II but distant from the B gene locus. The late-flowering phenotype of A. thaliana co-2 mutants was rescued by over-expression of BvCOL1 thereby suggesting functional equivalence with AtCO, and it is shown that BvCOL1 interacts appropriately with the endogenous downstream genes, AtFT and AtSOC1 in the transgenic plants. Curiously, BvCOL1 has a dawn-phased diurnal pattern of transcription, mimicking that of AtCOL1 and AtCOL2 while contrasting with AtCO. Taken together, these data suggest that BvCOL1 plays an important role in the photoperiod response of sugar beet. PMID:18495636

  18. A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors.

    PubMed

    Huntley, Stuart; Baggott, Daniel M; Hamilton, Aaron T; Tran-Gyamfi, Mary; Yang, Shan; Kim, Joomyeong; Gordon, Laurie; Branscomb, Elbert; Stubbs, Lisa

    2006-05-01

    Krüppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets.

  19. Two Novel Mutations in Myosin Binding Protein C Slow Causing Distal Arthrogryposis Type 2 in Two Large Han Chinese Families May Suggest Important Functional Role of Immunoglobulin Domain C2

    PubMed Central

    Li, Xuefu; Zhong, Bomeng; Han, Weitian; Zhao, Ning; Liu, Wei; Sui, Yu; Wang, Yawen; Lu, Yongping; Wang, Hong; Li, Jianxin; Jiang, Miao

    2015-01-01

    Distal arthrogryposes (DAs) are a group of disorders that mainly involve the distal parts of the limbs and at least ten different DAs have been described to date. DAs are mostly described as autosomal dominant disorders with variable expressivity and incomplete penetrance, but recently autosomal recessive pattern was reported in distal arthrogryposis type 5D. Mutations in the contractile genes are found in about 50% of all DA patients. Of these genes, mutations in the gene encoding myosin binding protein C slow MYBPC1 were recently identified in two families with distal arthrogryposis type 1B. Here, we described two large Chinese families with autosomal dominant distal arthrogryposis type 2(DA2) with incomplete penetrance and variable expressivity. Some unique overextension contractures of the lower limbs and some distinctive facial features were present in our DA2 pedigrees. We performed follow-up DNA sequencing after linkage mapping and first identified two novel MYBPC1 mutations (c.1075G>A [p.E359K] and c.956C>T [p.P319L]) responsible for these Chinese DA2 families of which one introduced by germline mosacism. Each mutation was found to cosegregate with the DA2 phenotype in each family but not in population controls. Both substitutions occur within C2 immunoglobulin domain, which together with C1 and the M motif constitute the binding site for the S2 subfragment of myosin. Our results expand the phenotypic spectrum of MYBPC1-related arthrogryposis multiplex congenita (AMC). We also proposed the possible molecular mechanisms that may underlie the pathogenesis of DA2 myopathy associated with these two substitutions in MYBPC1. PMID:25679999

  20. Late Embryogenesis Abundant (LEA) Constitutes a Large and Diverse Family of Proteins Involved in Development and Abiotic Stress Responses in Sweet Orange (Citrus sinensis L. Osb.)

    PubMed Central

    Pedrosa, Andresa Muniz; Martins, Cristina de Paula Santos; Gonçalves, Luana Pereira; Costa, Marcio Gilberto Cardoso

    2015-01-01

    Late Embryogenesis Abundant (LEA) proteins are an ubiquitous group of polypeptides that were first described to accumulate during plant seed dehydration, at the later stages of embryogenesis. Since then they have also been recorded in vegetative plant tissues experiencing water limitation and in anhydrobiotic bacteria and invertebrates and, thereby, correlated with the acquisition of desiccation tolerance. This study provides the first comprehensive study about the LEA gene family in sweet orange (Citrus sinensis L. Osb.), the most important and widely grown fruit crop around the world. A surprisingly high number (72) of genes encoding C. sinensis LEAs (CsLEAs) were identified and classified into seven groups (LEA_1, LEA_2, LEA_3 and LEA_4, LEA_5, DEHYDRIN and SMP) based on their predicted amino acid sequences and also on their phylogenetic relationships with the complete set of Arabidopsis thaliana LEA proteins (AtLEAs). Approximately 60% of the CsLEAs identified in this study belongs to the unusual LEA_2 group of more hydrophobic LEA proteins, while the other LEA groups contained a relatively small number of members typically hydrophilic. A correlation between gene structure and motif composition was observed within each LEA group. Investigation of their chromosomal localizations revealed that the CsLEAs were non-randomly distributed across all nine chromosomes and that 33% of all CsLEAs are segmentally or tandemly duplicated genes. Analysis of the upstream sequences required for transcription revealed the presence of various stress-responsive cis-acting regulatory elements in the promoter regions of CsLEAs, including ABRE, DRE/CRT, MYBS and LTRE. Expression analysis using both RNA-seq data and quantitative real-time RT-PCR (qPCR) revealed that the CsLEA genes are widely expressed in various tissues, and that many genes containing the ABRE promoter sequence are induced by drought, salt and PEG. These results provide a useful reference for further exploration of

  1. Late Embryogenesis Abundant (LEA) Constitutes a Large and Diverse Family of Proteins Involved in Development and Abiotic Stress Responses in Sweet Orange (Citrus sinensis L. Osb.).

    PubMed

    Pedrosa, Andresa Muniz; Martins, Cristina de Paula Santos; Gonçalves, Luana Pereira; Costa, Marcio Gilberto Cardoso

    2015-01-01

    Late Embryogenesis Abundant (LEA) proteins are an ubiquitous group of polypeptides that were first described to accumulate during plant seed dehydration, at the later stages of embryogenesis. Since then they have also been recorded in vegetative plant tissues experiencing water limitation and in anhydrobiotic bacteria and invertebrates and, thereby, correlated with the acquisition of desiccation tolerance. This study provides the first comprehensive study about the LEA gene family in sweet orange (Citrus sinensis L. Osb.), the most important and widely grown fruit crop around the world. A surprisingly high number (72) of genes encoding C. sinensis LEAs (CsLEAs) were identified and classified into seven groups (LEA_1, LEA_2, LEA_3 and LEA_4, LEA_5, DEHYDRIN and SMP) based on their predicted amino acid sequences and also on their phylogenetic relationships with the complete set of Arabidopsis thaliana LEA proteins (AtLEAs). Approximately 60% of the CsLEAs identified in this study belongs to the unusual LEA_2 group of more hydrophobic LEA proteins, while the other LEA groups contained a relatively small number of members typically hydrophilic. A correlation between gene structure and motif composition was observed within each LEA group. Investigation of their chromosomal localizations revealed that the CsLEAs were non-randomly distributed across all nine chromosomes and that 33% of all CsLEAs are segmentally or tandemly duplicated genes. Analysis of the upstream sequences required for transcription revealed the presence of various stress-responsive cis-acting regulatory elements in the promoter regions of CsLEAs, including ABRE, DRE/CRT, MYBS and LTRE. Expression analysis using both RNA-seq data and quantitative real-time RT-PCR (qPCR) revealed that the CsLEA genes are widely expressed in various tissues, and that many genes containing the ABRE promoter sequence are induced by drought, salt and PEG. These results provide a useful reference for further exploration of

  2. Late Embryogenesis Abundant (LEA) Constitutes a Large and Diverse Family of Proteins Involved in Development and Abiotic Stress Responses in Sweet Orange (Citrus sinensis L. Osb.).

    PubMed

    Pedrosa, Andresa Muniz; Martins, Cristina de Paula Santos; Gonçalves, Luana Pereira; Costa, Marcio Gilberto Cardoso

    2015-01-01

    Late Embryogenesis Abundant (LEA) proteins are an ubiquitous group of polypeptides that were first described to accumulate during plant seed dehydration, at the later stages of embryogenesis. Since then they have also been recorded in vegetative plant tissues experiencing water limitation and in anhydrobiotic bacteria and invertebrates and, thereby, correlated with the acquisition of desiccation tolerance. This study provides the first comprehensive study about the LEA gene family in sweet orange (Citrus sinensis L. Osb.), the most important and widely grown fruit crop around the world. A surprisingly high number (72) of genes encoding C. sinensis LEAs (CsLEAs) were identified and classified into seven groups (LEA_1, LEA_2, LEA_3 and LEA_4, LEA_5, DEHYDRIN and SMP) based on their predicted amino acid sequences and also on their phylogenetic relationships with the complete set of Arabidopsis thaliana LEA proteins (AtLEAs). Approximately 60% of the CsLEAs identified in this study belongs to the unusual LEA_2 group of more hydrophobic LEA proteins, while the other LEA groups contained a relatively small number of members typically hydrophilic. A correlation between gene structure and motif composition was observed within each LEA group. Investigation of their chromosomal localizations revealed that the CsLEAs were non-randomly distributed across all nine chromosomes and that 33% of all CsLEAs are segmentally or tandemly duplicated genes. Analysis of the upstream sequences required for transcription revealed the presence of various stress-responsive cis-acting regulatory elements in the promoter regions of CsLEAs, including ABRE, DRE/CRT, MYBS and LTRE. Expression analysis using both RNA-seq data and quantitative real-time RT-PCR (qPCR) revealed that the CsLEA genes are widely expressed in various tissues, and that many genes containing the ABRE promoter sequence are induced by drought, salt and PEG. These results provide a useful reference for further exploration of

  3. A Case of Nasu-Hakola Disease without Fractures or Consanguinity Diagnosed Using Exome Sequencing and Treated with Sodium Valproate

    PubMed Central

    Yamazaki, Kiyohiro; Yoshino, Yuta; Mori, Yoko; Ochi, Shinichiro; Yoshida, Taku; Ishimaru, Takashi; Ueno, Shu-ichi

    2015-01-01

    Nasu-Hakola disease (NHD) is a rare autosomal recessive neuropsychiatric disorder characterized by bone cysts, fractures, and cognitive impairment. Two genes are responsible for the development of NHD; TYROBP and TREM2. Although it presents with typical signs and symptoms, diagnosing this disease remains difficult. This case report describes a male with NHD with no family or past history of bone fractures who was diagnosed using exome sequencing. His frontal lobe psychiatric symptoms recovered partially following treatment with sodium valproate, but not with an antipsychotic. PMID:26598595

  4. Family Privilege

    ERIC Educational Resources Information Center

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  5. Family Literacy.

    ERIC Educational Resources Information Center

    Washington, Charles W., Ed.

    1996-01-01

    This newsletter theme issue focuses on the impact of learning disabilities within families, specifically families with low literacy skills. It explores the effectiveness of family literacy programs, examines the connection between the field of family literacy and learning disabilities (LD), and offers suggestions on how to work with students with…

  6. Putting the "family" back into family therapy.

    PubMed

    Breunlin, Douglas C; Jacobsen, Elizabeth

    2014-09-01

    In this article, we examine the field of family therapy by drawing a distinction between two forms of practice: Whole Family Therapy (WFT), defined as treating the whole family, and Relational Family Therapy (RFT), defined as working with a subsystem of the family or an individual while retaining a systemic lens. Our thesis is that the practice of WFT has been in decline for some time and steps must be taken to keep it from becoming a defunct practice. We consider the trajectory of WFT and RFT throughout the development of family therapy through reference to the people, the literature, training, and practice patterns associated with family therapy. We remind the reader of the many benefits of WFT and suggest that today WFT is likely to be practiced in conjunction with RFT and individual therapy. Since training of family therapists today is largely located in degree-granting programs, we identify constraints to including WFT in such programs. We conclude by offering suggestions that can enhance a program's ability to train students in WFT.

  7. Premutation for the Martin-Bell syndrome analyzed in a large Sardinian family: III. Molecular analysis with the StB12.3 probe

    SciTech Connect

    Grasso, M.; Perroni, L.; Dagna-Bricarelli, F.

    1996-08-09

    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.

  8. Asteroid families

    NASA Technical Reports Server (NTRS)

    Williams, James G.

    1991-01-01

    More than 100 asteroid families are presented in Williams. Several examples of cratering events are known including family numbers 150, 162, 169, and 189. These are recognizable as many small fragments adjacent to and to one side (in three dimensions) of a much larger cratered body. Family numbers 138 and 140 are adjacent in proper element space. In population they are an intermediate step between the long recognizable families and the more frequent less populated families. Family number 164 is the fifth most populous family in the belt. All members are faint and nothing is known of the physical properties.

  9. Association of PPARγ2 gene variant Pro12Ala polymorphism with hypertension and obesity in the aboriginal Qatari population known for being consanguineous

    PubMed Central

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

    2013-01-01

    Aim The aim of this study was to investigate the association of the Pro12Ala polymorphism of the human peroxisome proliferator-activated receptor gamma 2 (PPARγ2) 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 PPARγ2 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 PPARγ2Ala allele and obesity (P=0.740). Conclusion The current study revealed an association between the PPARγ2Ala allele and hypertension in Qatar’s population. On the other

  10. Muslim Families and Family Therapy.

    ERIC Educational Resources Information Center

    Daneshpour, Manijeh

    1998-01-01

    Examines the applicability of the Anglo-American models of family therapy to Muslim immigrant families. The differences in value systems are the Muslim families' preferences for greater connectedness, a less flexible and more hierarchical family structure, and an implicit communication style. Suggests that directions for change for Muslims need to…

  11. Cancer, Families, and Family Counselors.

    ERIC Educational Resources Information Center

    Duffy, Maureen; Gillig, Scott

    2003-01-01

    Examines the role of the family counselor in working with cancer patients and their families. Suggests ways in which the family counselor can work proactively with families in the area of cancer prevention and helping them cope more effectively with its impact on their lives. Uses a clinical case example to illustrate intervention with cancer…

  12. Street Men, Family Men: Race and Men's Extended Family Integration

    ERIC Educational Resources Information Center

    Sarkisian, Natalia

    2007-01-01

    Disorganization theories postulate that black men have largely abandoned their familial roles. Using the NSFH data, this article refutes the hypothesis of black men's familial disengagement by focusing on extended family integration. Black men are more likely than white men to live with or near extended kin, as well as to frequently see kin in…

  13. Family Violence and Family Physicians

    PubMed Central

    Herbert, Carol P.

    1991-01-01

    The acronym IDEALS summarizes family physicians' obligations when violence is suspected: to identify family violence; document injuries; educate families and ensure safety for victims; access resources and coordinate care; co-operate in the legal process; and provide support for families. Failure to respond reflects personal and professional experience and attitudes, fear of legal involvement, and lack of knowledge. Risks of intervention include physician burnout, physician overfunctioning, escalation of violence, and family disruption. PMID:21228987

  14. Familial nephropathy associated with hepatic type of glycogen storage disease.

    PubMed

    Sonobe, H; Ogawa, K; Takahashi, I

    1976-11-01

    The female patient was diagnosed as having Von Gierke's disease at 14 years of age, based on clinical manifestations, laboratory examination and liver biopsy. At 19 years of age she had uremia and died from its deterioration at 24 years of age. The parents were consanguineous, and a 27-year-old sister is presently hospitalized for renal insufficiency with hepatomegaly. On autopsy, the patient's kidneys were highly contracted and contained a number of small cysts, mainly in the medulla. Histological examination indicated periglomerular fibrosis, glomerular hyalinization, tubular atrophy or cystic dilatation and intersitial fibrosis with round cell infiltration. These findings correspond to Fanconi's familial juvenile nephronophthisis, except for age. The liver was markedly enlarged and indicated severe, glycogen deposits, but the kidney did not contain glycogen deposits. It can, therefore, be presumed that the renal lesions were not a secondary consequence of long-term glycogen deposits but that renal and hepatic lesions were associated with each other. PMID:1070908

  15. Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco.

    PubMed

    Mostefai, Rahima; Morice-Picard, Fanny; Boralevi, Franck; Sautarel, Michel; Lacombe, Didier; Stasia, Marie José; McGrath, John; Taïeb, Alain

    2008-11-01

    Three siblings from Morocco consanguineous family presented with cutaneous poikiloderma following postnatal ichthyosiform lesions, associated with papillomatous lesions, palmoplantar keratoderma, pachyonychia of toenails, fragile carious teeth, and lachrymal duct obstruction. Photosensitivity and blistering improved with age. Atrophic scars were prominent on the limbs. Neutropenia developed in the first year secondary to dysmyelopoiesis affecting the granulocyte lineage, associated with a polyclonal hypergammaglobulinemia. Several broncho-pulmonary infectious episodes complicated the evolution, and cystic fibrosis was first considered on the basis of repeated abnormal sweat chloride tests but not confirmed by molecular analyses. This autosomal recessive disorder matches that described originally as poikiloderma with neutropenia-Clericuzio type in Navajo Indians (OMIM 604173). It is discussed within the group of the major hereditary poikiloderma disorders, that is, Rothmund-Thomson syndrome, dyskeratosis congenita, and Kindler syndrome. PMID:18925663

  16. Familial Amyloidosis Cutis Dyschromica in Three Siblings: Report from Indonesia

    PubMed Central

    Hermawan, Melyawati; Rihatmadja, Rahadi; Sirait, Sondang Pandjaitan

    2014-01-01

    Amyloidosis cutis dyschromica (ACD) is an extremely rare type of primary cutaneous amyloidosis. To date there are fewer than 40 published cases worldwide; some were reported affecting several family members. Its resemblance to other common pigmentation disorders makes it rarely recognized at first sight. Our patient, the 12-year-old firstborn son of non-consanguineous parents presented with generalized mottled pigmentation starting from lower extremities. His siblings suffered from similar condition. The clue for diagnosis is the amyloid deposition in the papillary dermis. The etiology of ACD is still unknown, but genetic factors and ultraviolet radiation are implicated. It is proposed that disturbance of keratinocyte repair following ultraviolet radiation results in amyloid deposition. The treatment remains a challenge. Oral acitretin treatment, thought to repair keratinization defect, gave a slight improvement in our case. Our is the first case of ACD reported in Indonesia. PMID:25386328

  17. Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies

    PubMed Central

    Saqib, Muhammad Arif Nadeem; Nikopoulos, Konstantinos; Ullah, Ehsan; Sher Khan, Falak; Iqbal, Jamila; Bibi, Rabia; Jarral, Afeefa; Sajid, Sundus; Nishiguchi, Koji M.; Venturini, Giulia; Ansar, Muhammad; Rivolta, Carlo

    2015-01-01

    Inherited retinal dystrophies are phenotypically and genetically heterogeneous. This extensive heterogeneity poses a challenge when performing molecular diagnosis of patients, especially in developing countries. In this study, we applied homozygosity mapping as a tool to reduce the complexity given by genetic heterogeneity and identify disease-causing variants in consanguineous Pakistani pedigrees. DNA samples from eight families with autosomal recessive retinal dystrophies were subjected to genome wide homozygosity mapping (seven by SNP arrays and one by STR markers) and genes comprised within the detected homozygous regions were analyzed by Sanger sequencing. All families displayed consistent autozygous genomic regions. Sequence analysis of candidate genes identified four previously-reported mutations in CNGB3, CNGA3, RHO, and PDE6A, as well as three novel mutations: c.2656C > T (p.L886F) in RPGRIP1, c.991G > C (p.G331R) in CNGA3, and c.413-1G > A (IVS6-1G > A) in CNGB1. This latter mutation impacted pre-mRNA splicing of CNGB1 by creating a -1 frameshift leading to a premature termination codon. In addition to better delineating the genetic landscape of inherited retinal dystrophies in Pakistan, our data confirm that combining homozygosity mapping and candidate gene sequencing is a powerful approach for mutation identification in populations where consanguineous unions are common. PMID:25943428

  18. Familial gigantism.

    PubMed

    Herder, Wouter W de

    2012-01-01

    Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas. PMID:22584702

  19. Family Support.

    ERIC Educational Resources Information Center

    Wieck, Colleen, Ed.; McBride, Marijo, Ed.

    1990-01-01

    This "Feature Issue" of the quarterly journal "Impact" presents 19 brief articles on family support systems in the United States for persons with developmental disabilities and their families. Emphasis is on provisions of Public Law 99-457. Articles include: "Family Support in the United States: Setting a Course for the 1990s" (James Knoll);…

  20. Rural Families.

    ERIC Educational Resources Information Center

    Goetz, Kathy, Ed.

    1992-01-01

    This "special focus" journal issue consists of 13 individual articles on the theme of rural family programs relating to school, health services, church, and other institutions. It includes: (1) "Towards a Rural Family Policy" (Judith K. Chynoweth and Michael D. Campbell); (2) "Montana: Council for Families Collaborates for Prevention (Jean…

  1. Familial Gigantiform Cementoma: Case Report of an Unusual Clinical Manifestation and Possible Mechanism Related To "Calcium Steal Disorder".

    PubMed

    Ma, Chunyue; Wang, Hongwei; He, Guang; Qin, Xingjun

    2016-03-01

    Familial gigantiform cementoma is an exceedingly rare but distinct subtype of cemento-osseous-fibrous lesion. Undocumented radiographic changes and related bone metabolism disorder are herein hypothesized and discussed. We present an adolescent case with recurrent familial gigantiform cementoma who received surgical intervention in our hospital. Apart from typical multiquadrant and expansile abnormalies involving both jaws, he also suffered from several times of fractures in lower extremity. Furthermore, radiographic examinations of calvaria, pelvis, femoris, tibia, and fibula all revealed radiolucent areas signifying diffuse osteopenic bone losses. Some of his consanguineous relatives bore the same burden of fractures during pubertal period.Considering these polyostotic conditions, a correlation of congenital bone metabolism disorder in cases with familial gigantiform cementoma, named "calcium steal disorder," was thus proposed. Familial gigantiform cementoma is closely associated with "calcium steal disorder." Whole-body dual-energy absorptiometry should be considered as a routine examination for fracture-related risk prediction. PMID:26945411

  2. Cancerous leptomeningitis and familial congenital hypopituitarism.

    PubMed

    Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V

    2016-05-01

    People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies. PMID:26886902

  3. Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Effects of mutant gene dosage on phenotype.

    PubMed Central

    Pollak, M R; Chou, Y H; Marx, S J; Steinmann, B; Cole, D E; Brandi, M L; Papapoulos, S E; Menko, F H; Hendy, G N; Brown, E M

    1994-01-01

    Neonatal severe hyperparathyroidism is a rare life-threatening disorder characterized by very high serum calcium concentrations (> 15 mg/dl). Many cases have occurred in families with familial hypocalciuric hypercalcemia, a benign condition transmitted as a dominant trait. Among several hypothesized relationships between the two syndromes is the suggestion that neonatal severe hyperparathyroidism is the homozygous form of familial hypocalciuric hypercalcemia. To test this hypothesis, we refined the map location of the gene responsible for familial hypocalciuric hypercalcemia on chromosome 3q. Analyses in 11 families defined marker loci closely linked to the gene responsible for familial hypocalciuric hypercalcemia. These loci were then analyzed in four families with parental consanguinity and offspring with neonatal severe hyperparathyroidism. Each individual who was homozygous for loci that are closely linked to the gene responsible for familial hypocalciuric hypercalcemia had neonatal severe hyperparathyroidism. The calculated odds of linkage between these disorders of > 350,000:1 (lod score = 5.56). We conclude that dosage of the gene defect accounts for these widely disparate clinical phenotypes; a single defective allele causes familial hypocalciuric hypercalcemia, while two defective alleles causes neonatal severe hyperparathyroidism. PMID:8132750

  4. Families affected by deafness: hospital services uptake in a multiethnic population

    PubMed Central

    Yoong, S; Feltbower, R; Spencer, N; McKinney, P

    2005-01-01

    Aims: To examine the uptake of relevant hospital services by families with deaf children and to compare use of these services between Pakistani and white families. Methods: A total of 214 deaf children with amplification aids who attended their paediatric outpatient and school medical appointments from October 2000 to March 2003 were studied in an observational cohort study. Results: The demographic profile of both the Pakistani and white families was similar. Pakistani children had a statistically significant excess of the following risk factors: consanguineous marriages (86.4% Pakistani, 1.5% white), family history of deafness (66.4% Pakistani, 38.8% white), and family size (birth order >5: 12.8% Pakistani: 4.5% white). White children were more likely to have had post-meningitis deafness (1.4% Pakistani, 13.4% white) and congenital infections, or have dysmorphic features (5.0% Pakistani, 13.4% white). Overall the uptake of relevant hospital services by Pakistani and white families was very similar irrespective of an early or late diagnosis. There was an increased likelihood of white families declining cochlear implantation (17.6% Pakistani, 75.0% white). Conclusions: This study did not show significant differences in hospital service uptake despite different risk profiles for childhood deafness for both Pakistani and white families in Bradford. Among specialist services offered, cochlear implantation was more likely to be accessed by Pakistani families. PMID:15851424

  5. 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

    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

    2010-10-01

    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.

  6. Identification of the Chinese IVS-II-654 (C-->T) beta-thalassemia mutation in an immigrant Turkish family: recurrence or migration?

    PubMed

    Tadmouri, G O; Bilenoğlu, O; Kutlar, F; Markowitz, R B; Kutlar, A; Başak, A N

    1999-04-01

    In this study we describe the Chinese IVS-II-654 (C-->T) beta-thalassemia mutation for the first time in an immigrant Turkish family living in Istanbul and originating from Xanthe, Greece. Four members of the family, representing 3 generations, are heterozygous for this mutation. A detailed family history demonstrated a Greek origin for members of 5 generations with no records of migration or consanguineous marriages. Analysis of polymorphic nucleotides located at the 5' end of the beta-globin chromosomes bearing the IVS-II-654 mutation in the family described carried the (AT)9(T)5 type of microsatellite sequence and the ACATCCCCA haplotype. These 2 haplotype components favor a non-Eastern Asian origin for this chromosome, hence suggesting an independent origin for the IVS-II-654 mutation described in this family. PMID:10222649

  7. What makes a family reliable?

    NASA Technical Reports Server (NTRS)

    Williams, James G.

    1992-01-01

    Asteroid families are clusters of asteroids in proper element space which are thought to be fragments from former collisions. Studies of families promise to improve understanding of large collision events and a large event can open up the interior of a former parent body to view. While a variety of searches for families have found the same heavily populated families, and some searches have found the same families of lower population, there is much apparent disagreement between proposed families of lower population of different investigations. Indicators of reliability, factors compromising reliability, an illustration of the influence of different data samples, and a discussion of how several investigations perceived families in the same region of proper element space are given.

  8. Recurrent infections in partial complement factor I deficiency: evaluation of three generations of a Brazilian family

    PubMed Central

    Grumach, A S; Leitão, M F; Arruk, V G; Kirschfink, M; Condino-Neto, A

    2006-01-01

    We report here on the evaluation of a factor I-deficient Brazilian family (three generations, 39 members) with strong consanguinity. The complete factor I-deficient patients (n = 3) presented recurrent respiratory infections, skin infections and meningitis; one of them died after sepsis. They presented an impaired total haemolytic activity (CH50), low C3, low factor H and undetectable C3dg/C3d. Partial factor I deficiency was detected in 16 family members (normal low cut-off value was 25 µg/ml). Respiratory infections were the most common clinical occurrence among partial factor I-deficient relatives. Two of them were submitted to nephrectomy following recurrent urinary tract infections. An additional two heterozygous relatives presented with arthritis and rheumatic fever. Apparently, patients with partial factor I deficiency are also at higher risk for recurrent infections. Vaccination against capsulated bacteria and the eventual use of prophylactic antibiotics should be considered individually in this patient group. PMID:16412054

  9. Family Life.

    ERIC Educational Resources Information Center

    Naturescope, 1986

    1986-01-01

    Focuses on various aspects of mammal family life ranging from ways different species are born to how different mammals are raised. Learning activities include making butter from cream, creating birth announcements for mammals, and playing a password game on family life. (ML)

  10. Family Workshops

    ERIC Educational Resources Information Center

    Bennett, Dave; Rees-Jones, Tanny

    1978-01-01

    A Family Workshop is an informal, multidisciplined educational program for adults and children, organized by a team of teachers. This article discusses the Lavender Hill Family Workshop, one of many, which attempts to provide education in various subject areas for adults and for children while also integrating both objectives in order to educate…

  11. Family Empowerment.

    ERIC Educational Resources Information Center

    Sinclair, Mary F., Ed.; And Others

    1992-01-01

    This feature issue of IMPACT focuses on the empowerment of families with a member who has a developmental disability. It presents strategies and models for a collaborative, respectful approach to service provision, and presents the experiences of families in seeking support and assistance. Feature articles include "Two Generations of Disability: A…

  12. Family, Extended

    ERIC Educational Resources Information Center

    Patton, Jessica Rae

    2006-01-01

    Parents are a child's first and most influential teacher. People hear this truism often, yet nowhere has the author seen it more taken to heart than at Tower Street Elementary School. The school's efforts to form a true partnership with students' families--from involving families in the first day of school, to the principal making home visits, to…

  13. Family Potyviridae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The International Committee on the Taxonomy of Viruses potyvirus study group has revised the description of the family Potyviridae for inclusion in the ICTV 9th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of viral sp...

  14. FAMILY EMPIDIDAE.

    PubMed

    Rafael, José Albertino; Câmara, Josenir Teixeira

    2016-01-01

    Empididae is one of the biggest families of Diptera with around 3,000 known species. The family is poorly known in Colombia, with only six species reported and this work provides information on their distribution. No endemic genera or species have been recorded to date from Colombia. PMID:27395282

  15. Multicentre approaches to donor insemination in the French CECOS Federation: nationwide evaluation, donor matching, screening for genetic diseases and consanguinity. Centre d'Etudes et de Conservation des Oeufs et du Sperme humain.

    PubMed

    Le Lannou, D; Thépot, F; Jouannet, P

    1998-05-01

    The French CECOS Federation collates the results of its 22 sperm banks and provides annual reports on their activity. These records allow studies on many different aspects; annual nationwide evaluation, matching of donors and recipients, follow-up of pregnancies, research into artificial procreation, and natural fertility. Risk of transmitted hereditary disease is minimised by genetic screening which establishes the genealogy of donor candidates and includes karyotyping and other biological investigations when a particular risk is suspected. The real risk of consanguinity is very small. Limiting the number of children born from a given sperm donor can be defined at the local level. PMID:9665325

  16. Family Theory and Family Health Research

    PubMed Central

    Doherty, William J.

    1991-01-01

    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. PMID:21229056

  17. Family Health and Family Planning.

    ERIC Educational Resources Information Center

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    This document is made up of a selection of some of the papers distributed to participants in courses on "Family Health and Family Planning" which have been organized each year since 1973 by the International Children's Center and the World Health Organization Regional Office for Europe. Six courses, held between 1973 and 1978, brought together a…

  18. A family showing inheritance of the Anton blood group antigen AnWj and independence of AnWj from Lutheran.

    PubMed

    Poole, J; Levene, C; Bennett, M; Sela, R; van Alphen, L; Spruell, P J

    1991-12-01

    A 43-year-old Arab woman was found to be negative for the high incidence AnWj antigen and her serum contained anti-AnWj. Two of her seven siblings were also AnWj-negative, which provides evidence for the first time that the AnWj-negative phenotype may be an inherited character. Blood groups of the family, in which the parents of the proposita are consanguineous, show that AnWj is not part of the ABO, Rh, MNSs, Kell, Duffy, Kidd, Xg and, notably, Lutheran blood group systems and neither is it X or Y linked.

  19. The sodium-phosphate co-transporter SLC34A2, and pulmonary alveolar microlithiasis: Presentation of an inbred family and a novel truncating mutation in exon 3

    PubMed Central

    Vismara, Marco Favio Michele; Colao, Emma; Fabiani, Fernanda; Bombardiere, Francesco; Tamburrini, Oscar; Alessio, Caterina; Manti, Francesco; Pelaia, Gerolamo; Romeo, Pasquale; Iuliano, Rodolfo; Perrotti, Nicola

    2015-01-01

    Pulmonary alveolar microlithiasis is a disorder in which many tiny fragments (microliths) of calcium phosphate gradually accumulate in alveoli. Loss of function mutations in the gene SLC34A2 coding for the sodium phosphate co-transporter (NaPi-IIb) are responsible for genetic forms of alveolar microlithiasis. We now report a consanguineous Italian family from Calabria with two affected members segregating alveolar microlithiasis in a recessive fashion. We describe, for the first time, a novel loss of function mutation in the gene coding for NaPi-IIb. A careful description of the clinical phenotype is provided together with technical details for direct sequencing of the gene. PMID:26744662

  20. Family Issues

    MedlinePlus

    ... not mean that everyone gets along all the time. Conflicts are a part of family life. Many things can lead to conflict, such as illness, disability, addiction, job loss, school problems, and marital issues. Listening to ...

  1. Unusual families.

    PubMed

    Golombok, Susan

    2005-03-01

    The introduction of assisted reproduction has led to unusual forms of procreation. This article describes the social consequences of lesbian motherhood and of families headed by single heterosexual mothers. PMID:15819999

  2. Familial hypercholesterolemia

    MedlinePlus

    A diet low in cholesterol and saturated fat and rich in unsaturated fat may help to control your LDL level. People with a family history of this condition, particularly if both parents carry the defective ...

  3. Tomorrow's Family

    ERIC Educational Resources Information Center

    Pickett, Robert S.

    1977-01-01

    Author states that "...the traditional form of family which has been the norm in recent times in the West will persist, but will be forced to "move over" to accommodate other forms of domestic life." (Author)

  4. FAMILY PIOPHILIDAE.

    PubMed

    Wolff, Marta; Pérez, Sandra; Grisales, Diana

    2016-01-01

    Piophilidae is a little family poorly known in Colombia, with only Piophila casei (L.) and Stearibia nigriceps Meigen reported so far. This catalogue expands the distribution of these species to other localities in the country. PMID:27395294

  5. FAMILY BIBIONIDAE.

    PubMed

    Falaschi, Rafaela Lopes; Oliveira, Sarah Siqueira; Amorim, Dalton De Souza

    2016-06-14

    The Bibionidae are a family belonging to the suborder Bibionomorpha with four genera and 17 species known from Colombia. This work expands the distribution of these species to other localities in the country.

  6. FAMILY RHAGIONIDAE.

    PubMed

    Santos, Charles Morphy D; Carmo, Daniel D D

    2016-01-01

    The family Rhagionidae is one of the oldest Brachyeran lineages. Its monophyly is still uncertain. There are four rhagionid genera distributed in Neotropical Region but only three species of Chrysopilus are found in Colombia. PMID:27395270

  7. FAMILY PLATYSTOMATIDAE.

    PubMed

    Wendt, Lisiane Dilli

    2016-01-01

    Platystomatidae (Signal Flies) are one of the largest families of Tephritoidea, with about 1200 species and four subfamilies, worldwide distributed. However, Platystomatidae are not well represented in the New World, and in the Neotropical Region only four genera and 26 species, belonging to Platystomatinae, are recorded. The family is a group understudied in Colombia and only one species is recorded to the country. PMID:27395295

  8. Nursing support of family caregivers.

    PubMed

    Brackley, M H; Meadows, R F

    1989-01-01

    The relationship between caregiver and elder is a unique one. It cannot be compared to a mother-infant dyad; there is no role reversal. Family caregiving is undertaken out of a sense of filial obligation on the family's part coupled with the needs of the elderly person. The relationship that emerges is based on the dependency of one adult on another and is functional for the family and for society at large. We need families to continue to care for their elderly members at home and families need us to insure their survival. We must constantly be aware that care needs increase over the years, whereas family resources do not. Nursing by its very nature is tied to insuring that families are given the guidance and assistance with which to meet these needs. PMID:2789693

  9. Unusual evolutionary conservation and further species-specific adaptations of a large family of Nonclassical MHC class Ib genes across different degrees of genome ploidy in the amphibian subfamily Xenopodinae

    PubMed Central

    Edholm, Eva-Stina; Goyos, Ana; Taran, Joseph; De Jesús Andino, Francisco; Ohta, Yuko; Robert, Jacques

    2014-01-01

    Nonclassical MHC class Ib (class Ib) genes are a family of highly diverse and rapidly evolving genes wherein gene numbers, organization and expression markedly differ even among closely related species rendering class Ib phylogeny difficult to establish. Whereas among mammals there are few unambiguous class Ib gene orthologs, different amphibian species belonging to the anuran subfamily Xenopodinae exhibit an unusually high degree of conservation among multiple class Ib gene lineages. Comparative genomic analysis of class Ib gene loci of two divergent (~65 million years) Xenopodinae subfamily members X. laevis (allotetraploid) and X. tropicalis (diploid) shows that both species possess a large cluster of class Ib genes denoted as Xenopus/Silurana nonclassical (XNC/SNC). Our study reveals two distinct phylogenetic patterns among these genes: some gene lineages display a high degree of flexibility, as demonstrated by species-specific expansion and contractions, whereas other class Ib gene lineages have been maintained as monogenic subfamilies with very few changes in their nucleotide sequence across divergent species. In this second category, we further investigated the XNC/SNC10 gene lineage that in X. laevis is required for the development of a distinct semi-invariant T cell population. We report compelling evidence of the remarkable high degree of conservation of this gene lineage that is present in all 12 species of the Xenopodinae examined, including species with different degrees of ploidy ranging from 2, 4, 8 to 12N. This suggests that the critical role of XNC10 during early T cell development is conserved in amphibians. PMID:24771209

  10. Unusual evolutionary conservation and further species-specific adaptations of a large family of nonclassical MHC class Ib genes across different degrees of genome ploidy in the amphibian subfamily Xenopodinae.

    PubMed

    Edholm, Eva-Stina; Goyos, Ana; Taran, Joseph; De Jesús Andino, Francisco; Ohta, Yuko; Robert, Jacques

    2014-06-01

    Nonclassical MHC class Ib (class Ib) genes are a family of highly diverse and rapidly evolving genes wherein gene numbers, organization, and expression markedly differ even among closely related species rendering class Ib phylogeny difficult to establish. Whereas among mammals there are few unambiguous class Ib gene orthologs, different amphibian species belonging to the anuran subfamily Xenopodinae exhibit an unusually high degree of conservation among multiple class Ib gene lineages. Comparative genomic analysis of class Ib gene loci of two divergent (~65 million years) Xenopodinae subfamily members Xenopus laevis (allotetraploid) and Xenopus tropicalis (diploid) shows that both species possess a large cluster of class Ib genes denoted as Xenopus/Silurana nonclassical (XNC/SNC). Our study reveals two distinct phylogenetic patterns among these genes: some gene lineages display a high degree of flexibility, as demonstrated by species-specific expansion and contractions, whereas other class Ib gene lineages have been maintained as monogenic subfamilies with very few changes in their nucleotide sequence across divergent species. In this second category, we further investigated the XNC/SNC10 gene lineage that in X. laevis is required for the development of a distinct semi-invariant T cell population. We report compelling evidence of the remarkable high degree of conservation of this gene lineage that is present in all 12 species of the Xenopodinae examined, including species with different degrees of ploidy ranging from 2, 4, 8 to 12 N. This suggests that the critical role of XNC10 during early T cell development is conserved in amphibians.

  11. The changing American family.

    PubMed

    Thornton, A; Freedman, D

    1983-10-01

    This Bulletin documents recent changes in American family patterns resulting both from longterm trends in urbanization, industrialization, and economic growth and the disruption of the Great Depression and World War 2, as well as changed attitudes toward marriage, parenthood, divorce, and the roles of women. Following a postwar boom in the 1950s and 1960s, marriage rates have now fallen to levels observed in the early 20th century. Since 1970, the number of unmarried couples living together has more than tripled to 1.9 million in 1983. The divorce rate has now stabilized after more than doubling since 1960, but at the current level, 1/2 of all recent marriages will end in divorce. Most divorced persons remarry fairly quickly, often creating complex families of "step-relatives." With 19% of households with minor children now headed by a women with no husband present, up to 1/2 of all children will live for sometime in a fatherless family before age 18. Over 1/2 of all married women, including 49% of married mothers of preschool children, now hold a paid job outside the home. Working wives boost a family's income by an average 40% but still are expected to shoulder most responsiblility for home and childcare. White women now in their 20s say they expect to have an average of 2 children, but are delaying childbearing to such an extent that 29% could end up childless. Most of the elderly live on their own but usually near children whom they see frequently. Despite changes in traditional family patterns, Americans consistently report that a happy marriage and good family are the most important aspects of life. And though most Americans now live with few or no family members, they maintain active contact with a large network of family.

  12. Veritas Asteroid Family Still Holds Secrets?

    NASA Astrophysics Data System (ADS)

    Novakovic, B.

    2012-12-01

    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.

  13. AMH gene mutations in two Egyptian families with persistent müllerian duct syndrome.

    PubMed

    Mazen, Inas; Abdel Hamid, M S; El-Gammal, M; Aref, A; Amr, K

    2011-01-01

    The anti-müllerian hormone (AMH) is responsible for regression of müllerian ducts during male sexual differentiation. Mutations in the AMH gene or its type II receptor gene AMHR2 lead to persistence of the uterus and fallopian tubes in male children, i.e. persistent müllerian duct syndrome (PMDS). Both conditions are transmitted according to an autosomal recessive pattern and are symptomatic only in males. We report on 2 unrelated Egyptian consanguineous families with PMDS. The first family comprised 3 affected prepubertal sibs complaining of undescended testes. Pelvic exploration and laparotomy revealed müllerian duct derivatives. The other family was presenting with an adolescent male with impalpable left testis, and pelvic exploration showed remnants of fallopian tubes and rudimentary uterus. AMH levels were very low and almost undetectable in all affected patients in both families. Direct sequencing of the coding region of the AMH gene identified 2 homozygous mutations in exon 1, R95X in the first family and V12G in the second family. These data confirmed the autosomal recessive type of PMDS. Molecular investigation of this rare disorder in a larger number of cases with undescended testes in Egypt is warranted for proper diagnosis and genetic counseling. PMID:22188863

  14. FAMILY HYBOTIDAE.

    PubMed

    Ale-Rocha, Rosaly; De Freitas-Silva, Rafael Augusto Pinheiro

    2016-01-01

    Hybotidae is a diverse family of the order Diptera, suborder Brachycera, superfamily Empidoidea. Hybotid flies are generally yellow to black, are morphologically diverse, and are distributed worldwide. The monophyly of the family is based on: palpifer and fore tibial gland present, laterotergite bare and R4+5 unbranched. Hybotids are mainly predators and are usually found on the vegetation, logs and other surfaces, or in flight during displacement and forage. This catalogue, based on the study of specimens and available literature records, summarizes and updates the information on the Colombian fauna of Hybotidae, which includes 19 species distributed in six genera. PMID:27395283

  15. 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

    Frants, R.R.; Bakker, E.; Vossen, R.H.A.M.

    1994-09-01

    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.

  16. Familial leukemias.

    PubMed

    Wiernik, Peter H

    2015-02-01

    Familial leukemia has been described for more than 50 years but only recently have modern genetic techniques allowed for the investigation of the genome. Genome-wide association studies have identified a number of genetic sites that appear to relate to susceptibility to leukemia in certain families and occasionally to susceptibility to a specific leukemia in general. Many questions remain, including susceptibility to what? An oncogenic virus? An environmental chemical? Mutation of another gene induced by a heritable mutation-promoting gene?.Clinically important facts have been learned. Chronic lymphocytic leukemia (CLL) is by far the most common familial leukemia. Patients with CLL have approximately a 10% chance of a first-degree relative developing CLL, and even a greater chance of one developing monoclonal B-cell lymphocytosis which may be an asymptomatic forme fruste of the neoplasm. Furthermore, there may be an increased incidence of breast cancer in familial CLL pedigrees which raises the question of a common etiology for neoplasms in general, or at least a previously unrecognized relationship among them.

  17. Family Hypnotherapy.

    ERIC Educational Resources Information Center

    Araoz, Daniel L.; Negley-Parker, Esther

    1985-01-01

    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)

  18. FAMILY SCIARIDAE.

    PubMed

    Carvalho-Fernandes, Sheila Patrícia

    2016-01-01

    Sciaridae are a widely distributed family with high number of species. They are known as black fungus gnats due to their dark color and feeding activity. This catalogue presents 17 species from Colombia distributed in eight genera, and for each species the geographical distribution is provided.

  19. FAMILY SCATHOPHAGIDAE.

    PubMed

    Wolff, Marta; Grisales, Diana; Nihei, Silvio S

    2016-01-01

    Scathophagidae (Diptera, Calyptratae) is an uncommon group of flies. In Colombia there was no scientific record of this family until now. In this paper we report for the first time the genus Scatogera and the species S. primogenita Albuquerque, collected over 3000m. and previously collected in Ecuador. PMID:27395319

  20. Family Caregivers.

    ERIC Educational Resources Information Center

    Frazier, Billie H.

    This document contains a brief bibliography of peer-reviewed literature, with abstracts, on family caregiving. It is one of 12 bibliographies on aging prepared by the National Agricultural Library for its "Pathfinders" series of publications. Topics covered by the other 11 bibliographies include aging parents, adult children, dementia and…

  1. FAMILY SCIARIDAE.

    PubMed

    Carvalho-Fernandes, Sheila Patrícia

    2016-01-01

    Sciaridae are a widely distributed family with high number of species. They are known as black fungus gnats due to their dark color and feeding activity. This catalogue presents 17 species from Colombia distributed in eight genera, and for each species the geographical distribution is provided. PMID:27395255

  2. FAMILY ROPALOMERIDAE.

    PubMed

    Ale-Rocha, Rosaly

    2016-01-01

    Ropalomeridae is a small family with most species distributed in the Neotropical Region, from Mexico to Argentina, and only one Nearctic species. In Colombia, eight species distributed in four genera have been found. This catalogue, based on the study of specimens and available literature records, summarizes and updates the information on the Colombian fauna. PMID:27395300

  3. FAMILY RICHARDIIDAE.

    PubMed

    Wendt, Lisiane Dilli; Ale-Rocha, Rosaly

    2016-01-01

    Richardiidae are a family of "acalyptrate" Diptera represented by ca. 180 species distributed in the New World, mostly in the Neotropical region. The species that occur in Colombia have received little attention from taxonomists, and the great majority of them are known only from their type localities. Currently, 14 genera and 23 species are known to occur in the country. PMID:27395297

  4. Family Disruptions

    MedlinePlus

    ... and Returns Do you or your spouse frequently travel on business? These can be disruptive times for your child and for the family as ... these out-of-town trips. Spend as much time as it takes to explain where you are ... before and during your travels. You need to acknowledge and accept her feelings: " ...

  5. Woodhouse-Sakati Syndrome: Report of the First Tunisian Family with the C2orf37 Gene Mutation

    PubMed Central

    Hdiji, Olfa; Turki, Emna; Bouzidi, Nouha; Bouchhima, Imen; Damak, Mariem; Bohlega, Saeed; Mhiri, Chokri

    2016-01-01

    Woodhouse-Sakati syndrome (WSS) is an infrequent autosomal recessive condition characterized by progressive extrapyramidal signs, mental retardation, hypogonadism, alopecia, and diabetes mellitus. This syndrome belongs to a heterogeneous group of inherited neurodegenerative disorders characterized iron accumulation in the brain, and it is caused by mutations of the C2orf37 gene. We report the first Tunisian family with two affected sisters presenting with a phenotype suggestive of WSS. We examined the index patient presenting with movement disorders and mental retardation and then searched for similar cases in her family, which identified a sister with similar signs. We performed a genetic study that confirmed the diagnosis and revealed a c.436delC mutation of the C2orf37 gene. Therefore, WSS is an important consideration in patients presenting with movement disorders and intellectual disability. A high consanguinity contributes to the clustering of such rare autosomal recessive syndromes. PMID:27240811

  6. Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk.

    PubMed

    Thériault, Sébastien; Don-Wauchope, Andrew; Chong, Michael; Lali, Ricky; Morrison, Katherine M; Paré, Guillaume

    2016-01-01

    We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family. PMID:27678447

  7. Family planning Indonesia.

    PubMed

    Singarimbun, M

    1968-06-01

    The growth of family planning activities in Indonesia in the Postwar period is traced; and future prospects for family planning are assessed. Transmigration projects initiated by the Dutch and supported by President Sukarno after Indonesian independence as a means of decreasing population pressure on the island of Java, are identified as the only official response to the population problem until 1965. In the face of the government's opposition to the idea of birth control as a population control measure, the activities of the Indonesian Planned Parenthood Association (IPPA) after its founding in 1957 were limited to advising mothers on spacing of their children for health reasons. Statements made in support of a national family planning program by government officials at a 1967 IPPA Congress and on other occasions are noted. The major components of an approved national family planning program to start in 1969 are described. However, the government's policy as of late 1967 and early 1968 is characterized as one of mainly benevolent encouragement and help to voluntary organizations. The chief impediment to family planning in Indonesia is said to be a lack of motivation and the force of traditional values that favor large families. On the positive side are: 1) Studies showing considerable interest in birth control by the rural population; 2) A long history of traditional birth control practices; 3) The absence of outright opposition by religious groups to the principle of family planning. However, financial costs, the need for the training of personnel, and a general unawareness of the magnitude of the task lying ahead constitute other formidable obstacles.

  8. Familial pituitary adenomas.

    PubMed

    Vandeva, S; Vasilev, V; Vroonen, L; Naves, L; Jaffrain-Rea, M-L; Daly, A F; Zacharieva, S; Beckers, A

    2010-12-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas. PMID:20961530

  9. Pigmentary degenerative maculopathy as prominent phenotype in an Italian SPG56/CYP2U1 family.

    PubMed

    Leonardi, Luca; Ziccardi, Lucia; Marcotulli, Christian; Rubegni, Anna; Longobardi, Antonino; Serrao, Mariano; Storti, Eugenia; Pierelli, Francesco; Tessa, Alessandra; Parisi, Vincenzo; Santorelli, Filippo M; Carlo, Casali

    2016-04-01

    SPG56 is an autosomal recessive form of hereditary spastic paraplegia (HSP) associated with mutations in CYP2U1. There is no clear documentation of visual impairment in the few reported cases of SPG56, although this form is complex on clinical ground and visual deficit are extremely frequent in complicated HSP. We report three patients in a consanguineous family harboring the novel homozygous c.1168C>T (p.R390*) in SPG56/CYP2U1, and showing a pigmentary degenerative maculopathy associated with progressive spastic paraplegia. Furthermore, we characterized precisely the ophthalmologic phenotype through indirect ophthalmoscopy, retinal optical coherence tomography and visual evoked potentials. This is the first formal report of pigmentary degenerative maculopathy associated with a CYP2U1 homozygous mutation. PMID:26914923

  10. Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping

    SciTech Connect

    Kruglyak, L.; Daly, M.J.; Lander, E.S. |

    1995-02-01

    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.

  11. Family Therapy and Disturbed Families.

    ERIC Educational Resources Information Center

    Zuk, Gerald H., Ed.; Boszormenyi-Nagy, Ivan, Ed.

    Presented at a conference at which authors represented major theoretical positions in the field, most of the papers use family therapy as an important source of observations or ideas, or as a means to pinpoint methodological problems. Papers are grouped in sections as follows: four which introduce the reader to the field of specialization, provide…

  12. Filling the Glass: Gender Perspectives on Families

    ERIC Educational Resources Information Center

    Ferree, Myra Marx

    2010-01-01

    The challenge feminist scholarship posed to family studies has been largely met through the incorporation of research on gender dynamics within families and intersectional differences among them. Despite growing attention to gender as performance and power in more diverse families, the more difficult work of understanding the dynamics of change…

  13. Genetic epidemiology of Paget's disease of bone in italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of bone.

    PubMed

    Falchetti, Alberto; Di Stefano, Marco; Marini, Francesca; Ortolani, Sergio; Ulivieri, Massimo Fabio; Bergui, Simona; Masi, Laura; Cepollaro, Chiara; Benucci, Maurizio; Di Munno, Ombretta; Rossini, Maurizio; Adami, Silvano; Del Puente, Antonio; Isaia, Giancarlo; Torricelli, Francesca; Brandi, Maria Luisa

    2009-01-01

    Families affected by Paget's disease of bone frequently harbor mutations in the SQSTM1/p62 gene. In this multicentric study we collected 345 sporadic and 12 familial PDB cases throughout Italy, identifying 12 different mutations, 5 of which are newly reported and 3, D335E, A381V, and Y383X, external to the UBA domain. Subjects with truncating mutations, E396X, showed a significantly younger age at clinical diagnosis, while the Y383X subjects had a higher average number of affected skeletal sites. All the mutants exhibited the CGTG-H2 haplotype. In two pairs and one triad of unrelated Italian PDB families from different Italian regions, we detected a common SQSTM1/p62 mutation for each P392L, M404V, and G425R group. Since the CGTG-H2 haplotype frequency was also high in normal subjects, and genetic influence due to migratory fluxes of different ethnic groups exists in the Italian population, to refine the search for a more geographically specific founder effect, we extended the haplotype analysis in these families using polymorphic microsatellite repeat markers, within and flanking the SQSTM1/p62 locus, from chromosome 5q35, other than the exon 6 and 3'UTR polymorphisms. All mutant carriers from two of the three M404V families and from the G425R families exhibited common extended chromosome 5q35 haplotypes, IT01 and IT02, respectively, which may be reflecting influences of past migrations. This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population.

  14. Familial Hypercholesterolemia

    PubMed Central

    Bouhairie, Victoria Enchia; Goldberg, Anne Carol

    2015-01-01

    Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen and LDL apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with FH. It is important to increase awareness of this disorder in physicians and patients in order to reduce the burden of this disorder. PMID:25939291

  15. Familial hypercholesterolemia

    PubMed Central

    Turgeon, Ricky D.; Barry, Arden R.; Pearson, Glen J.

    2016-01-01

    Objective To summarize the pathophysiology, epidemiology, screening, diagnosis, and treatment of familial hypercholesterolemia (FH). Quality of evidence A PubMed search was conducted (inception to July 2014) for articles on pathophysiology, screening, diagnosis, and management of FH, supplemented with hand searches of bibliographies of guidelines and reviews. A supporting level of evidence for each recommendation was categorized as level I (randomized controlled trial or systematic review of randomized controlled trials), level II (observational study), or level III (expert opinion). The best available evidence is mostly level II or III. Main message Familial hypercholesterolemia affects 1 in 500 Canadians. Risk of a coronary event is high in these patients and is underestimated by risk calculators (eg, Framingham). Clinicians should screen patients according to guidelines and suspect FH in any patient with a premature cardiovascular event, physical stigmata of hypercholesterolemia, or an elevated plasma lipid level. Physicians should diagnose FH using either the Simon Broome or Dutch Lipid Network criteria. Management of heterozygous FH includes reducing low-density lipoprotein levels by 50% or more from baseline with high-dose statins and other lipid-lowering agents. Clinicians should refer any patient with homozygous FH to a specialized centre. Conclusion Familial hypercholesterolemia represents an important cause of premature cardiovascular disease in Canadians. Early identification and aggressive treatment of individuals with FH reduces cardiovascular morbidity and mortality. PMID:26796832

  16. AIDS and family planning.

    PubMed

    1992-01-01

    In 1991, an HIV prevention program advisor and a research/evaluation specialist for family planning programs discussed problems that affected HIV prevention and family planning services in Haiti before and after the coup of the Aristide government. Population activities began aimlessly in 1974 and HIV prevention efforts only began in 1988. After the coup, Haitians lost their newly found hope for meaningful development. All foreign assistance ended and they did not trust the army. In fact, other than essential child survival activities, no health and family planning services operated for several weeks. The situation grew worse after the economic embargo. 3 months after the coup, the US considered adding family planning assistance. Still little movement of condom, family planning, and health supplies left Port-au-Prince for the provinces which adversely affected all health related efforts. Condoms could no longer be distributed easily either in the socially marketed or US supplied condom distribution programs. Before the coup, HIV prevention and family planning programs depended on peer educators to educate the public (this approach made these programs quite successful), but the 2 experts feared that they would not return to those roles and that these programs would need to completely rebuild. Another concern was the large scale urban-rural migration making it difficult for them to continue care. Early in the AIDS epidemic, the Haitian government was on the defensive because the US considered Haitians as a high risk group so it did little to prevent HIV transmission. After 1988, HIV prevention activities in Haiti centered on raising awareness and personalizing the epidemic. The AIDS specialist noted, however, that a major obstacle to increasing knowledge is that AIDS is just 1 of many fatal diseases in Haiti. Moreover few health professionals in Haiti have ever had public health training. PMID:12159262

  17. FAMILY MYCETOPHILIDAE.

    PubMed

    Oliveira, Sarah Siqueira; Amorim, Dalton De Souza

    2016-06-14

    The Mycetophilidae include small fungus-gnats which life cycle is associated with fungi, especially of the larvae. The known diversity of the family in the Neotropical region is 1,145 species, but only some very few papers have been published on the Colombian species of Mycetophilidae, with records for the genera Docosia Winnertz, Paraleia Tonnoir, and Dziedzickia Johannsen. This catalogue gathers the information available on mycetophilids from Colombia, including genera and some species that for the first time are mentioned to occur in the country-as Leiella unicincta Edwards and Leiella zonalis Edwards.

  18. Family planning for travellers.

    PubMed

    Rustom, A

    1990-11-01

    A public health nurse from London describes the customs of nomadic people in the British Isles, known as "travellers," as they affect provision of family planning services. Most are of British or Irish stock, some migrate and others live in caravan sites all year. Their traditions dictate that men work and women are housewives. Early, often arranged, marriage, early childbearing and large families are the norm. Sex and contraception are not considered appropriate for discussion between the sexes, or in the presence of children. Large families and financial hardship force many women to space pregnancies. Women often have to hide contraceptives from their husbands, difficult in conditions without privacy. Therefore they prefer IUDs, but some use oral contraceptives, although sometimes erratically because most are illiterate. Traveller women are usually unwilling to do self-examination, as needed with IUDs. They often have difficulty attending regular Pap smear clinics. Cervical cancer rates are high. They experience discrimination in clinics, and need extra care about modesty. It is worth while to take time to develop trust in the clinical relationship, to deal with the traveller woman's uneasy among outsiders.

  19. Family and family therapy in the Netherlands.

    PubMed

    Wagenaar, Karin; Baars, Jan

    2012-04-01

    This article describes how families are functioning in the Netherlands, and how family therapy is used in mental healthcare. In the open Dutch society, new ideas are easily incorporated, as exemplified by the rapid introduction and growth of family therapy in the 1980s. In recent decades, however, family therapy has lost ground to other treatment models that are more individually orientated, and adhere to stricter protocols. This decline of family therapy has been exacerbated by recent budget cuts in mental healthcare. In regular healthcare institutes family therapy now has a marginal position at best, although family treatment models are used in specific areas such as forensic treatments. In addition, the higher trained family therapists have found their own niches to work with couples and families. We argue that a stronger position of family therapy would be beneficial for patients and for families, in order to counteract the strong individualization of Dutch society. PMID:22515464

  20. Roles within the Family

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Text Size Email Print Share Roles Within the Family Page Content Article Body Families are not democracies. ...