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Sample records for small consanguineous families

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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…

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. [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)

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. [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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. Missouri Small Farm Family Program. Revised.

    ERIC Educational Resources Information Center

    Enlow, George; And Others

    Records maintained by rural extension designees on the Missouri Small Farm Family Program, (initiated in 1972 by the cooperative extension service to help low income farm families learn to use available resources to improve their quality of life) provided data re: family characteristics, farm improvement progress, and improvement in the quality of…

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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%).

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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…

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. A Small Library in Family Planning.

    ERIC Educational Resources Information Center

    Planned Parenthood Federation of America, Inc., New York, NY.

    This annotated listing of books is intended as a reference for anyone seeking an authoritative introduction to population and family planning information, as a world, family, or individual concern. For each entry, the International Standard Book Number (ISBN) is provided if available. The number preceding each reference represents the…

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Small Samples, Big Challenges: Studying Atypical Family Forms

    ERIC Educational Resources Information Center

    Cheng, Simon; Powell, Brian

    2005-01-01

    We discuss the challenges of small-subsample sizes that family scholars often encounter when studying nontraditional or less common family types. We begin by identifying the general difficulties of using existing data in this line of research and then discuss potential solutions that may help researchers to avoid these problems. Using data from…

  1. Spectra of small Koronis family members

    NASA Astrophysics Data System (ADS)

    Thomas, C.; Rivkin, A.; Trilling, D.; Moskovitz, N.

    2014-07-01

    The space-weathering process and its implications for the relationships between S- and Q-type asteroids and ordinary chondrite meteorites are long-standing problems in asteroid science. Although the visible and near-infrared spectra of S- and Q-type objects qualitatively show the same absorption features and quantitatively show evidence of the same minerals, the S types display increased spectral slopes and muted absorption features compared to the Q types. This spectral mismatch is consistent with the effects of the space weathering process. Binzel et al. provided the missing link between Q- and S-type bodies in near-Earth space by showing a reddening of spectral slope in objects from 0.1 to 5 km that corresponded to the transition from Q- to S-type spectra. This result implied that size, and therefore age, is related to the relationship between Q- and S-type. The existence of Q-type objects in the main belt was not confirmed until Mothe-Diniz and Nesvorny (2008) found them in young S-type clusters. To investigate the trend from Q to S in the main belt, we examined space weathering within the old main-belt Koronis family using a spectrophotometric survey (Rivkin et al. 2011, Thomas et al. 2011). Rivkin et al. (2011) identified several potential Q-type objects within the Koronis family. Our Q-type candidates were identified using broad-band spectrophotometry and could not be taxonomically classified on that basis alone. We obtained follow-up visible and near-infrared spectral observations of our potential Q-type objects, (26970) Elias, (45610) 2000 DJ_{48}, and (37411) 2001 XF_{152}, using Gemini and Magellan. We will present the results of these spectral follow-up observations. Observations of (26970) Elias demonstrate that the object is more consistent with the average Q-type spectrum than the average S-type spectrum.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  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. 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. 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

  13. Small Family, Smart Family? Family Size and the IQ Scores of Young Men

    ERIC Educational Resources Information Center

    Black, Sandra E.; Devereux, Paul J.; Salvanes, Kjell G.

    2010-01-01

    This paper uses Norwegian data to estimate the effect of family size on IQ scores of men. Instrumental variables (IV) estimates using sex composition as an instrument show no significant negative effect of family size; however, IV estimates using twins imply that family size has a negative effect on IQ scores. Our results suggest that the effect…

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. SNP Haplotype Mapping in a Small ALS Family

    PubMed Central

    Krueger, Katherine A. Dick; Tsuji, Shoji; Fukuda, Yoko; Takahashi, Yuji; Goto, Jun; Mitsui, Jun; Ishiura, Hiroyuki; Dalton, Joline C.; Miller, Michael B.; Day, John W.; Ranum, Laura P. W.

    2009-01-01

    The identification of genes for monogenic disorders has proven to be highly effective for understanding disease mechanisms, pathways and gene function in humans. Nevertheless, while thousands of Mendelian disorders have not yet been mapped there has been a trend away from studying single-gene disorders. In part, this is due to the fact that many of the remaining single-gene families are not large enough to map the disease locus to a single site in the genome. New tools and approaches are needed to allow researchers to effectively tap into this genetic gold-mine. Towards this goal, we have used haploid cell lines to experimentally validate the use of high-density single nucleotide polymorphism (SNP) arrays to define genome-wide haplotypes and candidate regions, using a small amyotrophic lateral sclerosis (ALS) family as a prototype. Specifically, we used haploid-cell lines to determine if high-density SNP arrays accurately predict haplotypes across entire chromosomes and show that haplotype information significantly enhances the genetic information in small families. Panels of haploid-cell lines were generated and a 5 centimorgan (cM) short tandem repeat polymorphism (STRP) genome scan was performed. Experimentally derived haplotypes for entire chromosomes were used to directly identify regions of the genome identical-by-descent in 5 affected individuals. Comparisons between experimentally determined and in silico haplotypes predicted from SNP arrays demonstrate that SNP analysis of diploid DNA accurately predicted chromosomal haplotypes. These methods precisely identified 12 candidate intervals, which are shared by all 5 affected individuals. Our study illustrates how genetic information can be maximized using readily available tools as a first step in mapping single-gene disorders in small families. PMID:19479031

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Genetic risks and familial associations of small bowel carcinoma

    PubMed Central

    Shenoy, Santosh

    2016-01-01

    Adenocarcinoma of small intestines (SBA) is a relatively rare malignancy with poor outcomes due to delayed diagnosis. Fifty percent of patients have metastases on presentation and therefore early detection and treatment offers the best long term outcomes. Certain genetic polyposis syndromes and familial diseases are associated with increased risks for SBA. These include familial adenomatous polyposis (FAP), Lynch syndromes (LS), Juvenile polyposis syndrome, Peutz-Jeghers syndrome, Crohn’s disease (CD) and celiac disease. Mutations in APC gene, Mismatch repair genes, STK11 gene, and SMAD4 gene have been implicated for the genetic diseases respectively. While there are no specific inherited genetic mutations for CD, genome-wide association studies have established over 140 loci associated with CD. CpG island mutations with defects in mismatch repair genes have been identified in celiac disease. Significant diagnostic advances have occurred in the past decade and intuitively, it would seem beneficial to use these advanced modalities for surveillance of these patients. At present it is debatable and no clear data exists to support this approach except for established guidelines to diagnose duodenal polyps in FAP, and LS. Here we discuss the genetic alterations, cancer risks, signaling mechanisms and briefly touch the surveillance modalities available for these genetic and clinical syndromes. English language articles from PubMed/Medline and Embase was searched were collected using the phrases “small-bowel adenocarcinoma, genetics, surveillance, familial adenomatous polyposis, lynch syndromes, Peutz-Jeghers syndrome, juvenile polyposis syndrome, CD and celiac disease”. Figures, tables and schematic diagram to illustrate pathways are included in the review. PMID:27326320

  10. Genetic risks and familial associations of small bowel carcinoma.

    PubMed

    Shenoy, Santosh

    2016-06-15

    Adenocarcinoma of small intestines (SBA) is a relatively rare malignancy with poor outcomes due to delayed diagnosis. Fifty percent of patients have metastases on presentation and therefore early detection and treatment offers the best long term outcomes. Certain genetic polyposis syndromes and familial diseases are associated with increased risks for SBA. These include familial adenomatous polyposis (FAP), Lynch syndromes (LS), Juvenile polyposis syndrome, Peutz-Jeghers syndrome, Crohn's disease (CD) and celiac disease. Mutations in APC gene, Mismatch repair genes, STK11 gene, and SMAD4 gene have been implicated for the genetic diseases respectively. While there are no specific inherited genetic mutations for CD, genome-wide association studies have established over 140 loci associated with CD. CpG island mutations with defects in mismatch repair genes have been identified in celiac disease. Significant diagnostic advances have occurred in the past decade and intuitively, it would seem beneficial to use these advanced modalities for surveillance of these patients. At present it is debatable and no clear data exists to support this approach except for established guidelines to diagnose duodenal polyps in FAP, and LS. Here we discuss the genetic alterations, cancer risks, signaling mechanisms and briefly touch the surveillance modalities available for these genetic and clinical syndromes. English language articles from PubMed/Medline and Embase was searched were collected using the phrases "small-bowel adenocarcinoma, genetics, surveillance, familial adenomatous polyposis, lynch syndromes, Peutz-Jeghers syndrome, juvenile polyposis syndrome, CD and celiac disease". Figures, tables and schematic diagram to illustrate pathways are included in the review. PMID:27326320

  11. 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.

  12. 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.

  13. Diversity and evolution of the small multidrug resistance protein family

    PubMed Central

    Bay, Denice C; Turner, Raymond J

    2009-01-01

    Background Members of the small multidrug resistance (SMR) protein family are integral membrane proteins characterized by four α-helical transmembrane strands that confer resistance to a broad range of antiseptics and lipophilic quaternary ammonium compounds (QAC) in bacteria. Due to their short length and broad substrate profile, SMR proteins are suggested to be the progenitors for larger α-helical transporters such as the major facilitator superfamily (MFS) and drug/metabolite transporter (DMT) superfamily. To explore their evolutionary association with larger multidrug transporters, an extensive bioinformatics analysis of SMR sequences (> 300 Bacteria taxa) was performed to expand upon previous evolutionary studies of the SMR protein family and its origins. Results A thorough annotation of unidentified/putative SMR sequences was performed placing sequences into each of the three SMR protein subclass designations, namely small multidrug proteins (SMP), suppressor of groEL mutations (SUG), and paired small multidrug resistance (PSMR) using protein alignments and phylogenetic analysis. Examination of SMR subclass distribution within Bacteria and Archaea taxa identified specific Bacterial classes that uniquely encode for particular SMR subclass members. The extent of selective pressure acting upon each SMR subclass was determined by calculating the rate of synonymous to non-synonymous nucleotide substitutions using Syn-SCAN analysis. SUG and SMP subclasses are maintained under moderate selection pressure in comparison to integron and plasmid encoded SMR homologues. Conversely, PSMR sequences are maintained under lower levels of selection pressure, where one of the two PSMR pairs diverges in sequence more rapidly than the other. SMR genomic loci surveys identified potential SMR efflux substrates based on its gene association to putative operons that encode for genes regulating amino acid biogenesis and QAC-like metabolites. SMR subclass protein transmembrane domain

  14. 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.

  15. 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.

  16. [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.

  17. Family Portrait of the Small Inner Satellites of Jupiter

    NASA Technical Reports Server (NTRS)

    1997-01-01

    These images, taken by Galileo's solid state imaging system between November 1996 and June 1997, provide the first ever 'family portrait' of the four small, irregularly shaped moons that orbit Jupiter in the zone between the planet's ring and the larger Galilean satellites. The moons are shown in their correct relative sizes, with north approximately up in all cases. From left to right, arranged in order of increasing distance from Jupiter, are Metis (longest dimension is approximately 60 kilometers or 37 miles across), Adrastea (20 kilometers or 12 miles across), Amalthea (247 kilometers or 154 miles across), and Thebe (116 kilometers or 72 miles across). While Amalthea, the largest of these four tiny moons, was imaged by NASA's two Voyager spacecraft in 1979 with a resolution comparable to what is shown here, the new Galileo observations represent the first time that Metis, Adrastea, and Thebe have been seen as more than points of light.

    The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://www.jpl.nasa.gov/ galileo.

  18. 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.

  19. Establishing Order. Small Girls Write about Family Life.

    ERIC Educational Resources Information Center

    Hallden, Gunilla

    1994-01-01

    Analyzes children's own descriptions and interpretations of what family life is like or could be like. The research was designed to determine the children's perspective on childhood and parenthood. The article focuses on four girls and discusses their narratives using concepts from literary theory. The woman in control of family life is the…

  20. 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

  1. Promoting Population Stabilization: Incentives for Small Families. Worldwatch Paper 54.

    ERIC Educational Resources Information Center

    Jacobsen, Judith

    A wide variety of incentive and disincentive programs are presented in an effort to stabilize the population and prevent bankruptcy of physical, economic, and social resources, particularly in countries like India and China. Following an introduction, the document discusses several programs, including (1) the use of small one-time payments for…

  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 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.

  4. 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.

  5. A novel family of small proteins that affect plant development

    SciTech Connect

    John Charles Walker

    2011-04-29

    The DVL genes represent a new group of plant proteins that influence plant growth and development. Overexpression of DVL1, and other members of the DVL family, causes striking phenotypic changes. The DVL proteins share sequence homology in their C-terminal half. Point mutations in the C-terminal domain show it is necessary and deletion studies demonstrate the C-terminal domain is sufficient to confer the overexpression phenotypes. The phenotypes observed, and the conservation of the protein sequence in the plant kingdom, does suggest the DVL proteins have a role in modulating plant growth and development. Our working hypothesis is the DVL proteins function as regulators of cellular signaling pathways that control growth and development.

  6. Small families mean better health for mothers and kids.

    PubMed

    Mugumya, E

    1994-01-01

    The practice of family planning (FP) has been used since time immemorial to solve community, individual, and familial problems. There are Biblical references to incest being used to ensure the conception of children and to coitus interruptus being used to prevent conception. Pastoralists used cessation of breastfeeding of male calves to promote the conception and birth of more desirable female calves. The condom has ancient precursors made of animal intestines, and the IUD has a prototype in the stone commonly inserted in the uterus of a camel during long journeys to prevent conception. The issues of effectiveness, safety, and convenience that led to these ancient activities also inform the development and use of modern contraception. FP incorporates fertility control, both treatment for infertility and contraception; abortion is regarded as an indicator of a need for FP, not as part of FP. FP is justified on the grounds of human rights, because it allows an individual to choose whether or not to have a child; on the grounds of health, because maternal age and parity affect the health of the mother and child; on socioeconomic grounds, because overpopulation creates drains on already decreasing resources and because birth to unwed mothers creates difficulties for the children and for society; and on the grounds of improving the status of women because unwanted pregnancy causes women to abandon educational and employment opportunities. The maternal and child health and FP services in Uganda provide immunization, nutrition, prenatal and postpartum care, young child clinic services, school health education, and FP services. PMID:12318959

  7. 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

  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.

  9. 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.

  10. 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.

  11. 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.

  12. Small Families

    MedlinePlus

    ... on just one child, parents easily can become overprotective and indulgent without even realizing it. The child ... just one or two children, you may become overprotective and overly attentive. This may make your child ...

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Investigation of current university research concerning energy conversion and conservation in small single-family dwellings

    NASA Technical Reports Server (NTRS)

    Grossman, G. R.; Roberts, A. S., Jr.

    1975-01-01

    An investigation was made of university research concerning energy conversion and conservation techniques which may be applied in small single-family residences. Information was accumulated through published papers, progress reports, telephone conversations, and personal interviews. A synopsis of each pertinent investigation is given. Finally, a discussion of the synopses is presented and recommendations are made concerning the applicability of concepts for the design and construction of NASA-Langley Research Center's proposed Technology Utilization House in Hampton, Virginia.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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).

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. Campanulaceae: a family with small seeds that require light for germination

    PubMed Central

    Koutsovoulou, Katerina; Daws, Matthew I.; Thanos, Costas A.

    2014-01-01

    Background and Aims The Campanulaceae is a large cosmopolitan family, but is understudied in terms of germination, and seed biology in general. Small seed mass (usually in the range 10–200 µg) is a noteworthy trait of the family, and having small seeds is commonly associated with a light requirement. Thus, the purpose of this study was to investigate the effect of light on germination in 131 taxa of the Campanulaceae family, from all five continents of its distribution. Methods For all taxa, seed germination was tested in light (8 or 12 h photoperiod) and continuous darkness under constant and alternating temperatures. For four taxa, the effect of light on germination was examined over a wide range of temperatures on a thermogradient plate, and the possible substitution of the light requirement by gibberellic acid and nitrate was examined in ten taxa. Key Results For all 131 taxa, seed germination was higher in light than in darkness for every temperature tested. Across species, the light requirement decreased significantly with increasing seed mass. For larger seeded species, germination in the dark reached higher levels under alternating than under constant temperatures. Gibberellic acid promoted germination in darkness whereas nitrates partially substituted for a light requirement only in species showing some dark germination. Conclusions A light requirement for germination, observed in virtually all taxa examined, constitutes a collective characteristic of the family. It is postulated that smaller seeded taxa might germinate only on the soil surface or at shallow depths, while larger seeded species might additionally germinate when buried in the soil if cued to do so by fluctuating temperatures. PMID:24232382

  16. 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

  17. 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.

  18. How a Small Family Run Business Adopted Critical Reflection Action Learning Using Hand Drawn Images to Initiate Organisational Change

    ERIC Educational Resources Information Center

    Shepherd, Gary

    2016-01-01

    In this account of practice I would like to share my experiences of facilitating a Critical Reflection Action Learning (CRAL) set with a small family run business, struggling to make change and expand their services due to the problems they encountered in separating their business lives from their family lives. The account I present here is based…

  19. Small Science: Infants and Toddlers Experiencing Science in Everyday Family Life

    NASA Astrophysics Data System (ADS)

    Sikder, Shukla; Fleer, Marilyn

    2014-09-01

    Vygotsky (1987) stated that the restructured form of everyday concepts learned at home and in the community interact with scientific concepts introduced in formal school settings, leading to a higher level of scientific thinking for school-aged children. But, what does this mean for the scientific learning of infants and toddlers? What kinds of science learning are afforded at home during this early period of life? The study reported in this paper sought to investigate the scientific development of infants-toddlers (10 to 36 months) growing up in Bangladeshi families living in Australia and Singapore. Four families were studied over 2 years. Digital video observations were made of everyday family life and analysed using Vygotsky's theoretical framework of everyday concepts and scientific concepts (51 h of digital observations). While there are many possibilities for developing scientific concepts in infants-toddlers' everyday life, our study found four categories of what we have called small science: multiple possibilities for science; discrete science; embedded science and counter intuitive science. The findings of this study contribute to the almost non-existent literature into infants and toddlers' scientific development and advance new understandings of early childhood science education.

  20. Small Science: Infants and Toddlers Experiencing Science in Everyday Family Life

    NASA Astrophysics Data System (ADS)

    Sikder, Shukla; Fleer, Marilyn

    2015-06-01

    Vygotsky (1987) stated that the restructured form of everyday concepts learned at home and in the community interact with scientific concepts introduced in formal school settings, leading to a higher level of scientific thinking for school-aged children. But, what does this mean for the scientific learning of infants and toddlers? What kinds of science learning are afforded at home during this early period of life? The study reported in this paper sought to investigate the scientific development of infants-toddlers (10 to 36 months) growing up in Bangladeshi families living in Australia and Singapore. Four families were studied over 2 years. Digital video observations were made of everyday family life and analysed using Vygotsky's theoretical framework of everyday concepts and scientific concepts (51 h of digital observations). While there are many possibilities for developing scientific concepts in infants-toddlers' everyday life, our study found four categories of what we have called small science: multiple possibilities for science; discrete science; embedded science and counter intuitive science. The findings of this study contribute to the almost non-existent literature into infants and toddlers' scientific development and advance new understandings of early childhood science education.

  1. Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans.

    PubMed

    McEwan, Paul A; Scott, Paul G; Bishop, Paul N; Bella, Jordi

    2006-08-01

    The family of small leucine-rich repeat proteins and proteoglycans (SLRPs) contains several extracellular matrix molecules that are structurally related by a protein core composed of leucine-rich repeats (LRRs) flanked by two conserved cysteine-rich regions. The small proteoglycan decorin is the archetypal SLRP. Decorin is present in a variety of connective tissues, typically "decorating" collagen fibrils, and is involved in important biological functions, including the regulation of the assembly of fibrillar collagens and modulation of cell adhesion. Several SLRPs are known to regulate collagen fibrillogenesis and there is evidence that they may share other biological functions. We have recently determined the crystal structure of the protein core of decorin, the first such determination of a member of the SLRP family. This structure has highlighted several correlations: (1) SLRPs have similar internal repeat structures; (2) SLRP molecules are far less curved than an early model of decorin based on the three-dimensional structure of ribonuclease inhibitor; (3) the N-terminal and C-terminal cysteine-rich regions are conserved capping motifs. Furthermore, the structure shows that decorin dimerizes through the concave surface of its LRR domain, which has been implicated previously in its interaction with collagen. We have established that both decorin and opticin, another SLRP, form stable dimers in solution. Conservation of residues involved in decorin dimerization suggests that the mode of dimerization for other SLRPs will be similar. Taken together these results suggest the need for reevaluation of currently accepted models of SLRP interaction with their ligands.

  2. National impacts of the Weatherization Assistance Program in single-family and small multifamily dwellings

    SciTech Connect

    Brown, M.A.; Berry, L.G.; Balzer, R.A.; Faby, E.

    1993-05-01

    Since 1976, the US Department of Energy (DOE) has operated one of the largest energy conservation programs in the nation -- the low-income Weatherization Assistance Program. The program strives to increase the energy efficiency of dwellings occupied by low-income persons in order to reduce their energy consumption, lower their fuel bills, increase the comfort of their homes, and safeguard their health. It targets vulnerable groups including the elderly, people with disabilities, and families with children. The most recent national evaluation of the impacts of the Program was completed in 1984 based on energy consumption data for households weatherized in 1981. DOE Program regulations and operations have changed substantially since then: new funding sources, management principles, diagnostic procedures, and weatherization technologies have been incorporated. Many of these new features have been studied in isolation or at a local level; however, no recent evaluation has assessed their combined, nationwide impacts to date or their potential for the future. In 1990, DOE initiated such an evaluation. This evaluation is comprised of three ``impact`` studies (the Single-Family Study, High-Density Multifamily Study, and Fuel-Oil Study) and two ``policy`` studies. Altogether, these five studies will provide a comprehensive national assessment of the Weatherization Assistance Program as it existed in the 1989 Program Year (PY 1989). This report presents the results of the first phase of the Single-Family Study. It evaluates the energy savings and cost effectiveness of the Program as it has been applied to the largest portion of its client base -- low-income households that occupy single-family dwellings, mobile homes, and small (2- to 4-unit) multifamily dwellings. It is based upon a representative national sample that covers the full range of conditions under which the program was implemented in PY 1989.

  3. 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

  4. 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.

  5. 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.

  6. Novel Small Molecule Activators of the Trk Family of Receptor Tyrosine Kinases

    PubMed Central

    Obianyo, Obiamaka; Ye, Keqiang

    2012-01-01

    The Tropomyosin-related kinase (Trk) receptors are a subset of the receptor tyrosine kinase family with an important functionality in the regulation of neurotrophic signaling in the peripheral and central nervous system. As the receptors are able to mediate neuronal survival by associating with their respective neurotrophin ligands, many studies have focused on the therapeutic potential of generating small-molecule mimetic compounds that elicit agonistic effects similar to those of the natural protein ligands. To this end, various structure-based studies have led to the generation of bivalent peptide-based agonists and antibodies that selectively initiate Trk receptor signaling; however, these compounds do not possess the ideal characteristics of a potential drug. Additionally, the reliance of structure-based data to generate the compound libraries, limits the potential identification of novel chemical structures with desirable activity. Therefore, subsequent investigations utilized a cell-based apoptotic screen to facilitate the analysis of large, diverse chemical libraries of small molecules and quickly identify compounds with Trk-dependent antiapoptotic activity. Herein, we describe the Trk agonists that have been identified by this screening methodology and summarize their in vitro and in vivo neurotrophic activity as well as their efficacy in various neurological disease models, implicating their future utility as therapeutic compounds. PMID:22982231

  7. 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.

  8. 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.

  9. A resonant family of dynamically cold small bodies in the near-Earth asteroid belt

    NASA Astrophysics Data System (ADS)

    de la Fuente Marcos, C.; de la Fuente Marcos, R.

    2013-07-01

    Near-Earth objects (NEOs) moving in resonant, Earth-like orbits are potentially important. On the positive side, they are the ideal targets for robotic and human low-cost sample return missions and a much cheaper alternative to using the Moon as an astronomical observatory. On the negative side and even if small in size (2-50 m), they have an enhanced probability of colliding with the Earth causing local but still significant property damage and loss of life. Here, we show that the recently discovered asteroid 2013 BS45 is an Earth co-orbital, the sixth horseshoe librator to our planet. In contrast with other Earth's co-orbitals, its orbit is strikingly similar to that of the Earth yet at an absolute magnitude of 25.8, an artificial origin seems implausible. The study of the dynamics of 2013 BS45 coupled with the analysis of NEO data show that it is one of the largest and most stable members of a previously undiscussed dynamically cold group of small NEOs experiencing repeated trappings in the 1:1 commensurability with the Earth. This new resonant family is well constrained in orbital parameter space and it includes at least 10 other transient members: 2003 YN107, 2006 JY26, 2009 SH2 and 2012 FC71 among them. 2012 FC71 represents the best of both worlds as it is locked in a Kozai resonance and is unlikely to impact the Earth. These objects are not primordial and may have originated within the Venus-Earth-Mars region or in the main-belt, then transition to Amor-class asteroid before entering Earth's co-orbital region. Objects in this group could be responsible for the production of Earth's transient irregular natural satellites.

  10. 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.

  11. Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal

    PubMed Central

    Stoszko, Mateusz; De Crignis, Elisa; Rokx, Casper; Khalid, Mir Mubashir; Lungu, Cynthia; Palstra, Robert-Jan; Kan, Tsung Wai; Boucher, Charles; Verbon, Annelies; Dykhuizen, Emily C.; Mahmoudi, Tokameh

    2015-01-01

    Persistence of latently infected cells in presence of Anti-Retroviral Therapy presents the main obstacle to HIV-1 eradication. Much effort is thus placed on identification of compounds capable of HIV-1 latency reversal in order to render infected cells susceptible to viral cytopathic effects and immune clearance. We identified the BAF chromatin remodeling complex as a key player required for maintenance of HIV-1 latency, highlighting its potential as a molecular target for inhibition in latency reversal. Here, we screened a recently identified panel of small molecule inhibitors of BAF (BAFi's) for potential to activate latent HIV-1. Latency reversal was strongly induced by BAFi's Caffeic Acid Phenethyl Ester and Pyrimethamine, two molecules previously characterized for clinical application. BAFi's reversed HIV-1 latency in cell line based latency models, in two ex vivo infected primary cell models of latency, as well as in HIV-1 infected patient's CD4 + T cells, without inducing T cell proliferation or activation. BAFi-induced HIV-1 latency reversal was synergistically enhanced upon PKC pathway activation and HDAC-inhibition. Therefore BAFi's constitute a promising family of molecules for inclusion in therapeutic combinatorial HIV-1 latency reversal. PMID:26870822

  12. Myocilin variations and familial glaucoma in Taxiarchis, a small Greek village

    PubMed Central

    Konstas, Anastasios G. P.; Samples, John R.; Kaltsos, Kostantinos; Economou, Athanasios; Dimopoulos, Antonios; Georgiadou, Irene; Petersen, Michael B.

    2008-01-01

    Purpose To initiate a prospective study of glaucoma in a Greek village reported over 30 years ago to have several large families with primary open-angle glaucoma (POAG). Methods A random group of 126 villagers from Taxiarchis, Greece was examined in the village community center. The detailed evaluation included ophthalmic and general history, measurement of blood pressure, intraocular pressure (IOP), and central corneal thickness (CCT) as well as evaluation of the optic nerve status. Results The incidence of glaucoma approached 18% in this small isolated village. Myocilin variants were present in almost half of the individuals screened with Arg76Lys and Thr377Met being the most common finding (25% and 17%, respectively). Over half of the individuals with the Thr377Met mutation were diagnosed with glaucoma. Two of these patients were homozygous for the Thr377Met mutation. Three individuals with the Arg76Lys polymorphism had glaucoma; however, two of these individuals also had the Thr377Met mutation. Only two patients with pseudoexfoliation were identified. Conclusions The incidence of glaucoma and the Thr377Met MYOC mutation in this population is much higher than that reported for other European populations. PMID:18449353

  13. Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal.

    PubMed

    Stoszko, Mateusz; De Crignis, Elisa; Rokx, Casper; Khalid, Mir Mubashir; Lungu, Cynthia; Palstra, Robert-Jan; Kan, Tsung Wai; Boucher, Charles; Verbon, Annelies; Dykhuizen, Emily C; Mahmoudi, Tokameh

    2016-01-01

    Persistence of latently infected cells in presence of Anti-Retroviral Therapy presents the main obstacle to HIV-1 eradication. Much effort is thus placed on identification of compounds capable of HIV-1 latency reversal in order to render infected cells susceptible to viral cytopathic effects and immune clearance. We identified the BAF chromatin remodeling complex as a key player required for maintenance of HIV-1 latency, highlighting its potential as a molecular target for inhibition in latency reversal. Here, we screened a recently identified panel of small molecule inhibitors of BAF (BAFi's) for potential to activate latent HIV-1. Latency reversal was strongly induced by BAFi's Caffeic Acid Phenethyl Ester and Pyrimethamine, two molecules previously characterized for clinical application. BAFi's reversed HIV-1 latency in cell line based latency models, in two ex vivo infected primary cell models of latency, as well as in HIV-1 infected patient's CD4 + T cells, without inducing T cell proliferation or activation. BAFi-induced HIV-1 latency reversal was synergistically enhanced upon PKC pathway activation and HDAC-inhibition. Therefore BAFi's constitute a promising family of molecules for inclusion in therapeutic combinatorial HIV-1 latency reversal. PMID:26870822

  14. Consistent Small-Sample Variances for Six Gamma-Family Measures of Ordinal Association

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2009-01-01

    Gamma-family measures are bivariate ordinal correlation measures that form a family because they all reduce to Goodman and Kruskal's gamma in the absence of ties (1954). For several gamma-family indices, more than one variance estimator has been introduced. In previous research, the "consistent" variance estimator described by Cliff and colleagues…

  15. Service Family Support -- A Small-Scale Project of Educational Psychologists Working with Parents

    ERIC Educational Resources Information Center

    Hogg, Jane; Hart, Anne; Collins, Zoe V.

    2014-01-01

    Being in a Service family can be a difficult position for children and parents alike due to high levels of mobility, parental separation, and the remaining parent's stress and emotional well-being. A Service family is defined as a family with one or both parents employed by the Ministry of Defence (MOD). The current project looked at the…

  16. The squash aspartic proteinase inhibitor SQAPI is widely present in the cucurbitales, comprises a small multigene family, and is a member of the phytocystatin family.

    PubMed

    Christeller, John T; Farley, Peter C; Marshall, Richelle K; Anandan, Ananda; Wright, Michele M; Newcomb, Richard D; Laing, William A

    2006-12-01

    The squash (Cucurbita maxima) phloem exudate-expressed aspartic proteinase inhibitor (SQAPI) is a novel aspartic acid proteinase inhibitor, constituting a fifth family of aspartic proteinase inhibitors. However, a comparison of the SQAPI sequence to the phytocystatin (a cysteine proteinase inhibitor) family sequences showed approximately 30% identity. Modeling SQAPI onto the structure of oryzacystatin gave an excellent fit; regions identified as proteinase binding loops in cystatin coincided with regions of SQAPI identified as hypervariable, and tryptophan fluorescence changes were also consistent with a cystatin structure. We show that SQAPI exists as a small gene family. Characterization of mRNA and clone walking of genomic DNA (gDNA) produced 10 different but highly homologous SQAPI genes from Cucurbita maxima and the small family size was confirmed by Southern blotting, where evidence for at least five loci was obtained. Using primers designed from squash sequences, PCR of gDNA showed the presence of SQAPI genes in other members of the Cucurbitaceae and in representative members of Coriariaceae, Corynocarpaceae, and Begoniaceae. Thus, at least four of seven families of the order Cucurbitales possess member species with SQAPI genes, covering approximately 99% of the species in this order. A phylogenetic analysis of these Cucurbitales SQAPI genes indicated not only that SQAPI was present in the Cucurbitales ancestor but also that gene duplication has occurred during evolution of the order. Phytocystatins are widespread throughout the plant kingdom, suggesting that SQAPI has evolved recently from a phytocystatin ancestor. This appears to be the first instance of a cystatin being recruited as a proteinase inhibitor of another proteinase family.

  17. 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…

  18. Expression and strain variation of the novel “Small Open Reading Frame” 3 (smorf) multigene family in Babesia bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Small open reading frame (smorf) genes comprise the second largest Babesia bovis multigene family. All known 44 variant smorf genes are located in close chromosomal proximity to ves1 genes, which encode proteins that mediate cytoadhesion and contribute to immune evasion. In this study, we characte...

  19. 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

  20. 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…

  1. 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).

  2. Backbone assignment and secondary structure of Rnd1, an unusual Rho family small GTPase.

    PubMed

    Cao, Shufen; Mao, Xi'an; Liu, Deli; Buck, Matthias

    2013-10-01

    Rho GTPases have attracted considerable interest as signaling molecules due to their variety of functional roles in cells. Rnd1 is a relatively recently discovered Rho GTPase with no enzymatic activity against its bound GTP nucleotide, setting it apart from other family members. Research has revealed a critical role for Rnd1 not only in neurite outgrowth, dendrite development, axon guidance, but also in gastric cancer and in endothelial cells during inflammation. Structural information is crucial for understanding the mechanism that forms the basis for protein-protein interactions and functions, but until recently there were no reports of NMR studies directly on the Rnd1 protein. In this paper we report assignments for the majority of Rnd1 NMR resonances based on 2D and 3D NMR spectra. Rnd1 assignment was a challenging task, however, despite optimization strategies that have facilitated NMR studies of the protein (Cao and Buck in Small GTPase 2:295-304, 2012). Besides common triple-resonance experiments, 3D HNCA, 3D HN(CO)CA, 3D HNCO which are usually employed for sequence assignment, 3D NOESY experiments and specific labeling of 13 kinds of amino acids were also utilized to gain as many (1)H(N), (13)C, and (15)N resonances assignments as possible. For 170 cross peaks observed out of 183 possible mainchain N-H correlations in the (1)H-(15)N TROSY spectrum, backbone assignment was finally completed for 127 resonances. The secondary structure was then defined by chemical shifts and TALOS+ based on the assignments. The overall structure in solution compares well with that of Rnd1 in a crystal, except for two short segments, residues 77-83 and residues 127-131. Given that some features are shared among Rho GTPases, Rnd1 assignments are also compared with two other family members, Cdc42 and Rac1. The overall level of Rnd1 assignment is lower than for Cdc42 and Rac1, consistent with its lower stability and possibly increased internal dynamics. However, while the Rnd1

  3. Backbone assignment and secondary structure of Rnd1, an unusual Rho family small GTPase.

    PubMed

    Cao, Shufen; Mao, Xi'an; Liu, Deli; Buck, Matthias

    2013-10-01

    Rho GTPases have attracted considerable interest as signaling molecules due to their variety of functional roles in cells. Rnd1 is a relatively recently discovered Rho GTPase with no enzymatic activity against its bound GTP nucleotide, setting it apart from other family members. Research has revealed a critical role for Rnd1 not only in neurite outgrowth, dendrite development, axon guidance, but also in gastric cancer and in endothelial cells during inflammation. Structural information is crucial for understanding the mechanism that forms the basis for protein-protein interactions and functions, but until recently there were no reports of NMR studies directly on the Rnd1 protein. In this paper we report assignments for the majority of Rnd1 NMR resonances based on 2D and 3D NMR spectra. Rnd1 assignment was a challenging task, however, despite optimization strategies that have facilitated NMR studies of the protein (Cao and Buck in Small GTPase 2:295-304, 2012). Besides common triple-resonance experiments, 3D HNCA, 3D HN(CO)CA, 3D HNCO which are usually employed for sequence assignment, 3D NOESY experiments and specific labeling of 13 kinds of amino acids were also utilized to gain as many (1)H(N), (13)C, and (15)N resonances assignments as possible. For 170 cross peaks observed out of 183 possible mainchain N-H correlations in the (1)H-(15)N TROSY spectrum, backbone assignment was finally completed for 127 resonances. The secondary structure was then defined by chemical shifts and TALOS+ based on the assignments. The overall structure in solution compares well with that of Rnd1 in a crystal, except for two short segments, residues 77-83 and residues 127-131. Given that some features are shared among Rho GTPases, Rnd1 assignments are also compared with two other family members, Cdc42 and Rac1. The overall level of Rnd1 assignment is lower than for Cdc42 and Rac1, consistent with its lower stability and possibly increased internal dynamics. However, while the Rnd1

  4. Contribution of family labour to the profitability and competitiveness of small-scale dairy production systems in central Mexico.

    PubMed

    Posadas-Domínguez, Rodolfo Rogelio; Arriaga-Jordán, Carlos Manuel; Martínez-Castañeda, Francisco Ernesto

    2014-01-01

    The objective of this work was to determine the effect of family labour on the profitability and competitiveness of small-scale dairy farms in the highlands of Central Mexico. Economic data from 37 farms were analysed from a stratified statistical sampling with a Neyman assignment. Three strata were defined taking herd size as criterion. Stratum 1: herds from 3 to 9 cows plus replacements, Stratum 2: herds from 10 to 19 cows and Stratum 3: herds from 20 to 30 cows. The policy analysis matrix was used as the method to determine profitability and competitiveness. The coefficient of private profitability (CPP) when the economic cost of family labour is included in the cost structure was 8.0 %, 31.0 % and 46.0 %. When the economic cost of family labour is not included, CPP increase to 47.0 %, 57.0 % and 66.0 % for each strata, respectively. The private cost ratio (PCR) when family labour is included was 0.79, 0.51 and 0.42 for strata 1, 2 and 3, respectively. When family labour is not included, the PCR was 0.07, 0.25 and 0.26. Net profit per litre of milk including family labour was US$0.03 l(-1) for Stratum 1, US$0.09 for Stratum 2 and US$0.12 l(-1) for Stratum 3; but increased to $0.12, 0.14 and 0.15, respectively, when the economic cost of family labour is not included. It is concluded that family labour is a crucial factor in the profitability and competitiveness of small-scale dairy production. PMID:24097246

  5. Contribution of family labour to the profitability and competitiveness of small-scale dairy production systems in central Mexico.

    PubMed

    Posadas-Domínguez, Rodolfo Rogelio; Arriaga-Jordán, Carlos Manuel; Martínez-Castañeda, Francisco Ernesto

    2014-01-01

    The objective of this work was to determine the effect of family labour on the profitability and competitiveness of small-scale dairy farms in the highlands of Central Mexico. Economic data from 37 farms were analysed from a stratified statistical sampling with a Neyman assignment. Three strata were defined taking herd size as criterion. Stratum 1: herds from 3 to 9 cows plus replacements, Stratum 2: herds from 10 to 19 cows and Stratum 3: herds from 20 to 30 cows. The policy analysis matrix was used as the method to determine profitability and competitiveness. The coefficient of private profitability (CPP) when the economic cost of family labour is included in the cost structure was 8.0 %, 31.0 % and 46.0 %. When the economic cost of family labour is not included, CPP increase to 47.0 %, 57.0 % and 66.0 % for each strata, respectively. The private cost ratio (PCR) when family labour is included was 0.79, 0.51 and 0.42 for strata 1, 2 and 3, respectively. When family labour is not included, the PCR was 0.07, 0.25 and 0.26. Net profit per litre of milk including family labour was US$0.03 l(-1) for Stratum 1, US$0.09 for Stratum 2 and US$0.12 l(-1) for Stratum 3; but increased to $0.12, 0.14 and 0.15, respectively, when the economic cost of family labour is not included. It is concluded that family labour is a crucial factor in the profitability and competitiveness of small-scale dairy production.

  6. Testing the influence of family structure and outbreeding depression on heterozygosity-fitness correlations in small populations.

    PubMed

    Jourdan-Pineau, Helene; Folly, Joy; Crochet, Pierre-Andre; David, Patrice

    2012-11-01

    Theory predicts that positive heterozygosity-fitness correlations (HFCs) arise as a consequence of inbreeding, which is often assumed to have a strong impact in small, fragmented populations. Yet according to empirical data, HFC in such populations seem highly variable and unpredictable. We here discuss two overlooked phenomena that may contribute to this variation. First, in a small population, each generation may consist of a few families. This generates random correlations between particular alleles and fitness (AFCs, allele-fitness correlations) and results in too liberal tests for HFC. Second, in some contexts, small populations receiving immigrants may be more impacted by outbreeding depression than by inbreeding depression, resulting in negative rather than positive HFC. We investigated these processes through a case study in tadpole cohorts of Pelodytes punctatus living in small ponds. We provide evidence for a strong family structure and significant AFC in this system, as well as an example of negative HFC. By simulations, we show that this negative HFC cannot be a spurious effect of family structure, and therefore reflects outbreeding depression in the studied population. Our example suggests that a detailed examination of AFC and HFC patterns can provide valuable insights into the internal genetic structure and sources of fitness variation in small populations.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy

    PubMed Central

    Humphries, Brock; Yang, Chengfeng

    2015-01-01

    MicroRNAs (miRNAs) are a large family of small non-coding RNAs that negatively regulate protein-coding gene expression post-transcriptionally via base pairing between the 5′ seed region of a miRNA and the 3′ untranslated region (3′UTR) of a messenger RNA (mRNA). Recent evidence has supported the critical role that miRNAs play in many diseases including cancer. The miR-200 family consisting of 5 members (miR-200a, -200b, -200c, -141, -429) is an emerging miRNA family that has been shown to play crucial roles in cancer initiation and metastasis, and potentially be important for the diagnosis and treatment of cancer. While miR-200s were found to be critically involved in the metastatic colonization to the lungs in mouse mammary xenograft tumor models, a large number of studies demonstrated their strong suppressive effects on cell transformation, cancer cell proliferation, migration, invasion, tumor growth and metastasis. This review aims to discuss research findings about the role of the miR-200 family in cancer initiation, each step of cancer metastatic cascade, cancer diagnosis and treatment. A comprehensive summary of currently validated miR-200 targets is also presented. It is concluded that miR-200 family may serve as novel targets for the therapy of multiple types of cancer. PMID:25762624

  15. 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

  16. 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

  17. Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

    ClinicalTrials.gov

    2015-12-01

    Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

  18. 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.

  19. Detection of the YORP effect for small asteroids in the Karin family

    NASA Astrophysics Data System (ADS)

    Nesvorny, David; Carruba, Valerio; Vokrouhlicky, David

    2016-10-01

    The Karin family formed by a collisional breakup of a ~40-km parent asteroid only 5.75 Myr ago. The young age can be demonstrated by numerically integrating the orbits of Karin family members backward in time and showing the convergence of orbital elements. Previous work has pointed out that the convergence is not ideal if the backward integration only accounts for the gravitational perturbations from the Solar System planets. It improves when the thermal radiation force known as the Yarkovsky effect is accounted for. This method can be used to estimate the spin obliquities of Karin family members. Here we show that the obliquity distribution of diameter D=1‑2 km asteroids in the Karin family is bimodal, as expected if the YORP effect acted to move obliquities toward extreme values (0 or 180 deg). The measured magnitude of the effect is consistent with the standard YORP model. Specifically, the strength of the YORP effect is inferred to be roughly 70% of the nominal YORP strength obtained for a collection of random Gaussian spheroids. The surface thermal conductivity is found to be 0.07-0.2 W/m/K (thermal inertia 300‑500 in the SI units). These results are consistent with surfaces composed of rough and rocky regolith. The obliquity values predicted here for 480 members of the Karin cluster can be validated by the lightcurve inversion method. In broader context, the bimodal distribution of obliquities in the Karin cluster can be thought as an initial stage of dynamical evolution that later leads to a characteristically bi-lobed distribution of family members in the semimajor axis (e.g., Eos, Merxia or Erigone families).

  20. 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.

  1. 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.

  2. Family Involvement in Creative Teaching Practices for All in Small Rural Schools

    ERIC Educational Resources Information Center

    Vigo Arrazola, Begoña; Soriano Bozalongo, Juana

    2015-01-01

    Parental involvement is interpreted as a key form of support that can contribute to the establishment of inclusive practices in schools, but this can be difficult in sparsely populated areas. Using ethnographic methods of participant observation, informal conversations and document analysis, this article therefore focuses on family involvement…

  3. 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

  4. Interconversion of two GDP-bound conformations and their selection in an Arf-family small G protein.

    PubMed

    Okamura, Hideyasu; Nishikiori, Masaki; Xiang, Hongyu; Ishikawa, Masayuki; Katoh, Etsuko

    2011-07-13

    ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate in many cellular functions via their characteristic GTP/GDP conformational cycles, during which a nucleotide(∗)Mg(2+)-binding site communicates with a remote N-terminal helix. However, the conformational interplay between the nucleotides, the helix, the protein core, and Mg(2+) has not been fully delineated. Herein, we report a study of the dynamics of an Arf-family protein, Arl8, under various conditions by means of NMR relaxation spectroscopy. The data indicated that, when GDP is bound, the protein core, which does not include the N-terminal helix, reversibly transition between an Arf-family GDP form and another conformation that resembles the Arf-family GTP form. Additionally, we found that the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned former and latter conformations in a population-shift manner. Given the dynamics of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of an energy diagram.

  5. Space weathering of small Koronis family asteroids in the SDSS Moving Object Catalog

    NASA Astrophysics Data System (ADS)

    Thomas, Cristina A.; Trilling, David E.; Rivkin, Andrew S.

    2012-05-01

    Following the work of Rivkin et al. (Rivkin, A.S., Thomas, C.A., Trilling, D.E., Enga, M., Grier, J.A. [2011]. Icarus 211, 1294-1297) and Thomas et al. (Thomas, C.A., Rivkin, A.S, Trilling, D.E., Enga, M., Grier, J.A. [2011a]. Icarus 212, 158-166), we investigate space weathering trends in the Koronis family using the larger sample size of the Sloan Digital Sky Survey Moving Object Catalog. We confirm the trend in spectral slope seen in our earlier work and extend our results by investigating the trend in band depth (i - z color index) to show that Koronis family asteroids smaller than 4 km show the transition from fresh Q-type to weathered S-type surfaces.

  6. 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

  7. Expansion of the residential conservation service program to multi-family and small commercial buildings

    SciTech Connect

    1980-11-01

    Alternative regulatory provisions are considered which might permit achievement of the building energy conservation regulatory goals at a lower cost. Major issues, regulatory and legislative options, and cost-benefit analyses are discussed for multi-family and commercial buildings. The following are presented: related government programs, urban and community impact analysis, institutional impacts, energy cost, Residential Conservation Service coverage, methods of analysis, and regional studies. (MHR)

  8. A prognostic analysis of pediatrics central nervous system small cell tumors: evaluation of EGFR family gene amplification and overexpression

    PubMed Central

    2014-01-01

    Background Central nervous system (CNS) tumors are the most common solid tumors that occur in children, however there were few big-data follow-up analysis published in China. Overexpression of epidermal growth factor receptor (EGFR) family members was reported on glioblastoma (GBM) and medulloblastoma (MB) before. However, the correlation between EGFR family members expression with prognosis of MB, supratentorial primitive neuroectodermal tumor (PNET) and small cell GBM is unclear in Chinese children. Methods A retrospective and survival analysis was performed on children (age ≤ 16 years) diagnosed as CNS primary small cell tumors in the Affiliated Provincial Hospital, Shandong University from 2000 to 2012, including MB (n = 44), PNET (n = 8) and small cell GBM (n = 19). The expression of EGFR, ERBB-2, ERBB-3 and ERBB-4 were detected by immunohistochemistry (IHC). The fluorescence in situ hybridization (FISH) was used to observe the amplification of EGFR and ERBB-2 gene. Results Median survival times of MBs, small GBMs and PNETs were 23 ± 6.7 months, 8 ± 4.7 months and 10 ± 1.4 months. Expression and amplification of ERBB-2, ERBB-3 and ERBB-4 were not observed in all tumor samples. The multiply Cox regression suggested the overexpression and amplification of EGFR were negative prognostic factors for MB. Radiotherapy had the positive function for all pediatric patients. Conclusion Overexpression of EGFR predicts poor outcomes of MBs, small cell GBMs and PNETs, suggesting those three CNS tumor subtypes can be considered as one group for the potential common mechanism. The current individual treatment and big data analysis of pediatric CNS embryonal tumors and GBM continues to be very challenging in China. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7649640001237474 PMID:24986561

  9. 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

  10. Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members.

    PubMed Central

    Frost, J A; Xu, S; Hutchison, M R; Marcus, S; Cobb, M H

    1996-01-01

    The mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that are regulated by distinct extracellular stimuli. The currently known members include extracellular signal-regulated protein kinase 1 (ERK1), ERK2, the c-Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs), and p38 MAP kinases. We find that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2. Rat MAP/ERK kinase kinase 1 can stimulate the activity of each of these MAP kinases. Although neither activated Rac nor the PAKs stimulate ERK2 activity, overexpression of either dominant negative Rac2 or the N-terminal regulatory domain of PAK1 inhibits Ras-mediated activation of ERK2, suggesting a permissive role for Rac in the control of the ERK pathway. Furthermore, constitutively active Rac2, Cdc42hs, and RhoA synergize with an activated form of Raf to increase ERK2 activity. These findings reveal a previously unrecognized connection between Rho family small G proteins and the ERK pathway. PMID:8668187

  11. New Opportunitie s for Small Satellite Programs Provided by the Falcon Family of Launch Vehicles

    NASA Astrophysics Data System (ADS)

    Dinardi, A.; Bjelde, B.; Insprucker, J.

    2008-08-01

    The Falcon family of launch vehicles, developed by Space Exploration Technologies Corporation (SpaceX), are designed to provide the world's lowest cost access to orbit. Highly reliable, low cost launch services offer considerable opportunities for risk reduction throughout the life cycle of satellite programs. The significantly lower costs of Falcon 1 and Falcon 9 as compared with other similar-class launch vehicles results in a number of new business case opportunities; which in turn presents the possibility for a paradigm shift in how the satellite industry thinks about launch services.

  12. Intra-family differences in efficacy of inactivation of small, non-enveloped viruses.

    PubMed

    Nims, Raymond W; Zhou, S Steve

    2016-09-01

    The use of specific model viruses for validating viral purification process steps and for assessing the efficacies of viral disinfectants is based, in part, on the assumption that viral susceptibilities to such treatments will be similar for different members, including different genera, within a given viral family. This assumption is useful in cases where cell-based infectivity assays or laboratory strains for the specific viruses of interest might not exist. There are some documented cases, however, where exceptions to this assumption exist. In this paper, we discuss some of the more striking cases of intra-family differences in susceptibilities to inactivation steps used for downstream viral purification steps in biologics manufacture (e.g. heat inactivation, low pH, and guanidinium hydrochloride inactivation) and to specific viral disinfectants (e.g. alcohols, hydrogen peroxide, and quaternary ammonium-containing disinfectants) that might be employed for facility/equipment disinfection. The results suggest that care should be taken when extrapolating viral inactivation susceptibilities from specific model viruses to different genera or even to different members of the same genus. This should be taken into consideration by regulatory agencies and biologics manufacturers designing viral clearance and facility disinfection validation studies, and developers and evaluators of viral disinfectants. PMID:27473770

  13. 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.

  14. 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

  15. Label-based routing for a family of small-world Farey graphs

    PubMed Central

    Zhai, Yinhu; Wang, Yinhe

    2016-01-01

    We introduce an informative labelling method for vertices in a family of Farey graphs, and deduce a routing algorithm on all the shortest paths between any two vertices in Farey graphs. The label of a vertex is composed of the precise locating position in graphs and the exact time linking to graphs. All the shortest paths routing between any pair of vertices, which number is exactly the product of two Fibonacci numbers, are determined only by their labels, and the time complexity of the algorithm is O(n). It is the first algorithm to figure out all the shortest paths between any pair of vertices in a kind of deterministic graphs. For Farey networks, the existence of an efficient routing protocol is of interest to design practical communication algorithms in relation to dynamical processes (including synchronization and structural controllability) and also to understand the underlying mechanisms that have shaped their particular structure. PMID:27167605

  16. Label-based routing for a family of small-world Farey graphs

    NASA Astrophysics Data System (ADS)

    Zhai, Yinhu; Wang, Yinhe

    2016-05-01

    We introduce an informative labelling method for vertices in a family of Farey graphs, and deduce a routing algorithm on all the shortest paths between any two vertices in Farey graphs. The label of a vertex is composed of the precise locating position in graphs and the exact time linking to graphs. All the shortest paths routing between any pair of vertices, which number is exactly the product of two Fibonacci numbers, are determined only by their labels, and the time complexity of the algorithm is O(n). It is the first algorithm to figure out all the shortest paths between any pair of vertices in a kind of deterministic graphs. For Farey networks, the existence of an efficient routing protocol is of interest to design practical communication algorithms in relation to dynamical processes (including synchronization and structural controllability) and also to understand the underlying mechanisms that have shaped their particular structure.

  17. Gamma Convergence of a Family of Surface-Director Bending Energies with Small Tilt

    NASA Astrophysics Data System (ADS)

    Lussardi, Luca; Röger, Matthias

    2016-03-01

    We prove a Gamma-convergence result for a family of bending energies defined on smooth surfaces in R^3 equipped with a director field. The energies strongly penalize the deviation of the director from the surface unit normal and control the derivatives of the director. Such types of energies arise, for example, in a model for bilayer membranes introduced by Peletier and Röger (Arch Ration Mech Anal 193(3), 475-537, 2009). Here we prove in three space dimensions in the vanishing-tilt limit a Gamma-liminf estimate with respect to a specific curvature energy. In order to obtain appropriate compactness and lower semi-continuity properties we use tools from geometric measure theory, in particular the concept of generalized Gauss graphs and curvature varifolds.

  18. Label-based routing for a family of small-world Farey graphs.

    PubMed

    Zhai, Yinhu; Wang, Yinhe

    2016-01-01

    We introduce an informative labelling method for vertices in a family of Farey graphs, and deduce a routing algorithm on all the shortest paths between any two vertices in Farey graphs. The label of a vertex is composed of the precise locating position in graphs and the exact time linking to graphs. All the shortest paths routing between any pair of vertices, which number is exactly the product of two Fibonacci numbers, are determined only by their labels, and the time complexity of the algorithm is O(n). It is the first algorithm to figure out all the shortest paths between any pair of vertices in a kind of deterministic graphs. For Farey networks, the existence of an efficient routing protocol is of interest to design practical communication algorithms in relation to dynamical processes (including synchronization and structural controllability) and also to understand the underlying mechanisms that have shaped their particular structure. PMID:27167605

  19. Label-based routing for a family of small-world Farey graphs.

    PubMed

    Zhai, Yinhu; Wang, Yinhe

    2016-01-01

    We introduce an informative labelling method for vertices in a family of Farey graphs, and deduce a routing algorithm on all the shortest paths between any two vertices in Farey graphs. The label of a vertex is composed of the precise locating position in graphs and the exact time linking to graphs. All the shortest paths routing between any pair of vertices, which number is exactly the product of two Fibonacci numbers, are determined only by their labels, and the time complexity of the algorithm is O(n). It is the first algorithm to figure out all the shortest paths between any pair of vertices in a kind of deterministic graphs. For Farey networks, the existence of an efficient routing protocol is of interest to design practical communication algorithms in relation to dynamical processes (including synchronization and structural controllability) and also to understand the underlying mechanisms that have shaped their particular structure.

  20. Tandem Duplication Events in the Expansion of the Small Heat Shock Protein Gene Family in Solanum lycopersicum (cv. Heinz 1706)

    PubMed Central

    Krsticevic, Flavia J.; Arce, Débora P.; Ezpeleta, Joaquín; Tapia, Elizabeth

    2016-01-01

    In plants, fruit maturation and oxidative stress can induce small heat shock protein (sHSP) synthesis to maintain cellular homeostasis. Although the tomato reference genome was published in 2012, the actual number and functionality of sHSP genes remain unknown. Using a transcriptomic (RNA-seq) and evolutionary genomic approach, putative sHSP genes in the Solanum lycopersicum (cv. Heinz 1706) genome were investigated. A sHSP gene family of 33 members was established. Remarkably, roughly half of the members of this family can be explained by nine independent tandem duplication events that determined, evolutionarily, their functional fates. Within a mitochondrial class subfamily, only one duplicated member, Solyc08g078700, retained its ancestral chaperone function, while the others, Solyc08g078710 and Solyc08g078720, likely degenerated under neutrality and lack ancestral chaperone function. Functional conservation occurred within a cytosolic class I subfamily, whose four members, Solyc06g076570, Solyc06g076560, Solyc06g076540, and Solyc06g076520, support ∼57% of the total sHSP RNAm in the red ripe fruit. Subfunctionalization occurred within a new subfamily, whose two members, Solyc04g082720 and Solyc04g082740, show heterogeneous differential expression profiles during fruit ripening. These findings, involving the birth/death of some genes or the preferential/plastic expression of some others during fruit ripening, highlight the importance of tandem duplication events in the expansion of the sHSP gene family in the tomato genome. Despite its evolutionary diversity, the sHSP gene family in the tomato genome seems to be endowed with a core set of four homeostasis genes: Solyc05g014280, Solyc03g082420, Solyc11g020330, and Solyc06g076560, which appear to provide a baseline protection during both fruit ripening and heat shock stress in different tomato tissues. PMID:27565886

  1. Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules

    SciTech Connect

    Leão, Mariana; Gomes, Sara; Bessa, Cláudia; Soares, Joana; Raimundo, Liliana; Monti, Paola; Fronza, Gilberto; Pereira, Clara; Saraiva, Lucília

    2015-01-01

    In this work, the yeast Saccharomyces cerevisiae was used to individually study human p53, p63 (full length and truncated forms) and p73. Using this cell system, the effect of these proteins on cell proliferation and death, and the influence of MDM2 and MDMX on their activities were analyzed. When expressed in yeast, wild-type p53, TAp63, ΔNp63 and TAp73 induced growth inhibition associated with S-phase cell cycle arrest. This growth inhibition was accompanied by reactive oxygen species production and autophagic cell death. Furthermore, they stimulated rapamycin-induced autophagy. On the contrary, none of the tested p53 family members induced apoptosis either per se or after apoptotic stimuli. As previously reported for p53, also TAp63, ΔNp63 and TAp73 increased actin expression levels and its depolarization, suggesting that ACT1 is also a p63 and p73 putative yeast target gene. Additionally, MDM2 and MDMX inhibited the activity of all tested p53 family members in yeast, although the effect was weaker on TAp63. Moreover, Nutlin-3a and SJ-172550 were identified as potential inhibitors of the p73 interaction with MDM2 and MDMX, respectively. Altogether, the yeast-based assays herein developed can be envisaged as a simplified cell system to study the involvement of p53 family members in autophagy, the modulation of their activities by specific interactors (MDM2 and MDMX), and the potential of new small molecules to modulate these interactions. - Highlights: • p53, p63 and p73 are individually studied in the yeast S. cerevisiae. • p53 family members induce ROS production, cell cycle arrest and autophagy in yeast. • p53 family members increase actin depolarization and expression levels in yeast. • MDM2 and MDMX inhibit the activity of p53 family members in yeast. • Yeast can be a useful tool to study the biology and drugability of p53, p63 and p73.

  2. Evaluation of a Teaching Kit for Family and Consumer Science Classrooms: Motivating Students to Use a Food Thermometer with Small Cuts of Meat

    ERIC Educational Resources Information Center

    Edwards, Zena; Edlefsen, Miriam; Hillers, Virginia; McCurdy, Sandra M.

    2005-01-01

    The U.S. Dept. of Agriculture recommends use of food thermometers to safely cook small cuts of meat, yet most consumers do not use them. Consumers lack knowledge about how and why to use food thermometers with small cuts of meat. Opportunities exist for family and consumer science classes to provide education about thermometers to adolescents, who…

  3. 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

  4. Molecular characterization and evolution of the SPRR family of keratinocyte differentiation markers encoding small proline-rich proteins

    SciTech Connect

    Gibbs, S.; Fijneman, R.; Wiegant, J.; Van De Putte, P.; Backendorf, C. ); Van Kessel, A.D. )

    1993-06-01

    SPRR genes (formerly SPR) encode a novel class of polypeptides (small proline rich proteins) that are strongly induced during differentiation of human epidermal keratinocytes in vitro and in vivo. Recently the authors found that the N- and C-terminal domains of these proteins show strong sequence homology to loricrin and involucrin, suggesting that SPRR proteins constitute a new class of cornified envelope precursor proteins. Here they show that SPRR proteins are encoded by closely related members of a gene family, consisting of two genes for SPRR1, approximately seven genes for SPRR2, and a single gene for SPRR3. All SPRR genes are closely linked within a 300-kb DNA segment on human chromosome 1 band q21-q22, a region where the related loricrin and involucrin genes have also been mapped. The most characteristic feature of the SPRR gene family resides in the structure of the central segments of the encoded polypeptides that are built up from tandemly repeated units of either eight (SPRR1 and SPRR3) or nine (SPRR2) amino acids with the general consensus *K*PEP**. Sequencing data of the different members, together with their clustered chromosomal organization, strongly suggest that this gene family has evolved from a single progenitor gene by multiple intra- and intergenic duplications. Analysis of the different SPRR subfamilies reveals a gene-specific bias to either intra- or intergenic duplication. The authors propose that a process of homogenization has acted on the different members of one subfamily, whereas the different subfamilies appear to have diverged from each other, at the levels of both protein structure and gene regulation. 25 refs., 7 figs., 2 tab.

  5. Substance P-stimulated interleukin-8 expression in human colonic epithelial cells involves Rho family small GTPases.

    PubMed Central

    Zhao, Dezheng; Kuhnt-Moore, Sabina; Zeng, Huiyan; Pan, Amy; Wu, Jack S; Simeonidis, Simos; Moyer, Mary P; Pothoulakis, Charalabos

    2002-01-01

    Interaction of the neuropeptide substance P (SP) and its neurokinin-1 receptor (NK-1R) plays an important role in the pathophysiology of intestinal inflammation. SP is known to stimulate production of interleukin (IL)-6 and IL-8 in the U-373-MG human astrocytoma cell line via activation of p38 MAPK (mitogen-activated protein kinase) and nuclear factor (NF)-kappaB, respectively. However, the signalling mechanisms by which SP-NK-1R interaction induces NF-kappaB activation and IL-8 expression are still not clear. In this study we demonstrate that SP stimulates IL-8 secretion and IL-8 promoter activity in the NCM460 non-transformed human colonic epithelial cell line transfected with NK-1R cDNA. Our results indicate that inhibition of endogenous Rho family proteins (RhoA, Rac1 and Cdc42) by their respective dominant negative mutants significantly decreases SP-induced IL-8 secretion and IL-8 promoter activity. We also demonstrate that SP rapidly activates RhoA, Rac1 and Cdc42 and that co-expression of the dominant negative mutants of RhoA, Rac1 and Cdc42 in NK-1R cDNA-transfected NCM460 cells significantly inhibits SP-induced NF-kappaB-dependent gene expression. These results demonstrate that Rho family small GTPases RhoA, Rac1 and Cdc42 are novel signal transducers for SP-stimulated IL-8 expression. PMID:12169092

  6. 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

  7. 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.

  8. The Role of Irreversible HER Family Inhibition in the Treatment of Patients with Non-Small Cell Lung Cancer

    PubMed Central

    2011-01-01

    Small-molecule tyrosine kinase inhibitors (TKIs) of the human epidermal growth factor receptor (HER) include the reversible epidermal growth factor receptor (EGFR/HER-1) inhibitors gefitinib and erlotinib. EGFR TKIs have demonstrated activity in the treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations; however, multiple mechanisms of resistance limit the benefit of these drugs. Although resistance to EGFR TKIs can be intrinsic and correlated with molecular lesions such as in Kirsten rat sarcoma viral oncogene homolog (KRAS; generally observed in a wild-type EGFR background), acquired resistance to EGFR TKIs can evolve in the setting of activating EGFR mutations, such as in the case of EGFR T790M mutations. Several irreversible inhibitors that target multiple members of the HER family simultaneously are currently in clinical development for NSCLC and may have a role in the treatment of TKI-sensitive and TKI-resistant disease. These include PF00299804, an inhibitor of EGFR/HER-1, HER-2, and HER-4, and afatinib (BIBW 2992), an inhibitor of EGFR/HER-1, HER-2, and HER-4. Results of large, randomized trials of these agents may help to determine their potential for the treatment of NSCLC. PMID:22016476

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Crystal structure of M-Ras reveals a GTP-bound "off" state conformation of Ras family small GTPases.

    PubMed

    Ye, Min; Shima, Fumi; Muraoka, Shin; Liao, Jingling; Okamoto, Hidetsugu; Yamamoto, Masaki; Tamura, Atsuo; Yagi, Naoto; Ueki, Tatzuo; Kataoka, Tohru

    2005-09-01

    Although some members of Ras family small GTPases, including M-Ras, share the primary structure of their effector regions with Ras, they exhibit vastly different binding properties to Ras effectors such as c-Raf-1. We have solved the crystal structure of M-Ras in the GDP-bound and guanosine 5'-(beta,gamma-imido)triphosphate (Gpp(NH)p)-bound forms. The overall structure of M-Ras resembles those of H-Ras and Rap2A, except that M-Ras-Gpp(NH)p exhibits a distinctive switch I conformation, which is caused by impaired intramolecular interactions between Thr-45 (corresponding to Thr-35 of H-Ras) of the effector region and the gamma-phosphate of Gpp(NH)p. Previous 31P NMR studies showed that H-Ras-Gpp(NH)p exists in two interconverting conformations, states 1 and 2. Whereas state 2 is a predominant form of H-Ras and corresponds to the "on" conformation found in the complex with effectors, state 1 is thought to represent the "off" conformation, whose tertiary structure remains unknown. 31P NMR analysis shows that free M-Ras-Gpp(NH)p predominantly assumes the state 1 conformation, which undergoes conformational transition to state 2 upon association with c-Raf-1. These results indicate that the solved structure of M-Ras-Gp-p(NH)p corresponds to the state 1 conformation. The predominance of state 1 in M-Ras is likely to account for its weak binding ability to the Ras effectors, suggesting the importance of the tertiary structure factor in small GTPase-effector interaction. Further, the first determination of the state 1 structure provides a molecular basis for developing novel anti-cancer drugs as compounds that hold Ras in the state 1 "off" conformation. PMID:15994326

  15. 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…

  16. Use of small incentives for increasing participation and reducing dropout in a family drug-use prevention program in a Spanish sample.

    PubMed

    Díaz, Susana Al-Halabí; Pérez, José Manuel Errasti

    2009-01-01

    Poor participation rates represent one of the most serious problems facing family-based drug-use prevention programs. Strategies involving incentives have been used to increase recruitment and retention of the target population of such interventions, but in Spain, such strategies for modifying behavior are unusual. The goal of the research was to study the use of small financial incentives (euro10 voucher) as a strategy to increase attendance and reduce dropout in a family drug-prevention program applied in the school context. Participants were 211 pupils (aged 12-13) and their parents. The results show that small financial incentives can be useful to increase the attendance of families in prevention programs and to reduce dropout. PMID:20001690

  17. 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.

  18. 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.

  19. [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.

  20. 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

  1. 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

  2. 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.

  3. The mammalian Rab family of small GTPases: definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily.

    PubMed

    Pereira-Leal, J B; Seabra, M C

    2000-08-25

    The Rab/Ypt/Sec4 family forms the largest branch of the Ras superfamily of GTPases, acting as essential regulators of vesicular transport pathways. We used the large amount of information in the databases to analyse the mammalian Rab family. We defined Rab-conserved sequences that we designate Rab family (RabF) motifs using the conserved PM and G motifs as "landmarks". The Rab-specific regions were used to identify new Rab proteins in the databases and suggest rules for nomenclature. Surprisingly, we find that RabF regions cluster in and around switch I and switch II regions, i.e. the regions that change conformation upon GDP or GTP binding. This finding suggests that specificity of Rab-effector interaction cannot be conferred solely through the switch regions as is usually inferred. Instead, we propose a model whereby an effector binds to RabF (switch) regions to discriminate between nucleotide-bound states and simultaneously to other regions that confer specificity to the interaction, possibly Rab subfamily (RabSF) specific regions that we also define here. We discuss structural and functional data that support this model and its general applicability to the Ras superfamily of proteins.

  4. The importance of interaction with membrane lipids through the pleckstrin homology domain of the guanine nucleotide exchange factor for rho family small guanosine triphosphatase, FLJ00018.

    PubMed

    Kimura, Shinji; Sato, Katsuya; Banno, Yoshiko; Nagase, Takahiro; Ueda, Hiroshi

    2013-01-01

    FLJ00018, a heterotrimeric guanosine 5'-triphosphate (GTP)-binding protein (G protein) Gβγ subunit-activated guanine nucleotide exchange factor for Rho family small GTPases, regulates cellular responses, including cell morphological changes and gene transcriptional regulation, and targets the cellular membranes. FLJ00018 contains a Dbl homology (DH) domain in addition to a pleckstrin homology (PH) domain. Here we show that the PH domain of FLJ00018 is required for FLJ00018-induced, serum response element-dependent gene transcription. Although the PH domain of KIAA1415/P-Rex1, another Gβγ subunit-activated guanine nucleotide exchange factor for Rho family small GTPases, binds to phosphatidylinositol 3,4,5-triphosphate and phosphatidylinositol 3,4-bisphosphate, the PH domain of FLJ00018 binds to polyphosphoinositides including phosphatidylinositol 4,5-bisphosphate, and phosphatidic acid. These results suggest that FLJ00018 is targeted via its PH domain to cellular membranes.

  5. 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

  6. 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.

  7. 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

  8. Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families

    PubMed Central

    2012-01-01

    Background Hereditary hearing loss is one of the most common heterogeneous disorders, and genetic variants that can cause hearing loss have been identified in over sixty genes. Most of these hearing loss genes have been detected using classical genetic methods, typically starting with linkage analysis in large families with hereditary hearing loss. However, these classical strategies are not well suited for mutation analysis in smaller families who have insufficient genetic information. Methods Eighty known hearing loss genes were selected and simultaneously sequenced by targeted next-generation sequencing (NGS) in 8 Korean families with autosomal dominant non-syndromic sensorineural hearing loss. Results Five mutations in known hearing loss genes, including 1 nonsense and 4 missense mutations, were identified in 5 different genes (ACTG1, MYO1F, DIAPH1, POU4F3 and EYA4), and the genotypes for these mutations were consistent with the autosomal dominant inheritance pattern of hearing loss in each family. No mutational hot-spots were revealed in these Korean families. Conclusion Targeted NGS allowed for the detection of pathogenic mutations in affected individuals who were not candidates for classical genetic studies. This report is the first documenting the effective use of an NGS technique to detect pathogenic mutations that underlie hearing loss in an East Asian population. Using this NGS technique to establish a database of common mutations in Korean patients with hearing loss and further data accumulation will contribute to the early diagnosis and fundamental therapies for hereditary hearing loss. PMID:22938506

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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…

  15. Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities

    PubMed Central

    Ahmed-Belkacem, Abdelhakim; Colliandre, Lionel; Ahnou, Nazim; Nevers, Quentin; Gelin, Muriel; Bessin, Yannick; Brillet, Rozenn; Cala, Olivier; Douguet, Dominique; Bourguet, William; Krimm, Isabelle; Pawlotsky, Jean-Michel; Guichou, Jean- François

    2016-01-01

    Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections. PMID:27652979

  16. The importance of molecular profiling in predicting response to epidermal growth factor receptor family inhibitors in non-small-cell lung cancer: focus on clinical trial results.

    PubMed

    Tsao, Anne S; Papadimitrakopoulou, Vassiliki

    2013-07-01

    In recent years, the epidermal growth factor receptor (EGFR) family has become a key focus of non-small-cell lung cancer biology and targeted therapies, such as the reversible EGFR tyrosine kinase inhibitors erlotinib and gefitinib. Initially, response to these agents was associated with certain demographic and clinical characteristics; subsequently, it was discovered that these subgroups were more likely to harbor specific mutations in the EGFR gene that enhanced tumor response. However, the presence of these mutations does not equate to therapeutic success. Other aspects of EGFR family signaling, including other types of EGFR mutations, EGFR protein expression, EGFR gene amplification, mediators of downstream signaling, and other receptors with similar downstream pathways may all play a role in response or resistance to treatment. The identification of these and other molecular determinants is driving the development of novel therapies designed to achieve improved clinical outcomes in patients.

  17. 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

  18. The RJL family of small GTPases is an ancient eukaryotic invention probably functionally associated with the flagellar apparatus.

    PubMed

    Elias, Marek; Archibald, John M

    2009-08-01

    A patchily distributed gene family is often taken as evidence for horizontal gene transfer (HGT) events, but it may also result solely from multiple gene losses. The RJL family of uncharacterised Ras-like GTPases was previously suggested to have undergone HGT events between protists and deuterostome metazoans, owing to the apparent absence of RJL in intermediate groups (Nepomuceno-Silva, J.L., de Melo, L.D., Mendonca, S.M., Paixao, J.C., Lopes, U.G., 2004. RJLs: a new family of Ras-related GTP-binding proteins. Gene 327, 221-232). We have reanalysed the phylogenetic distribution and phylogeny of the RJL family, taking advantage of the recent expansion of sequence data available from diverse eukaryotes. We found that RJL orthologs are much more widely distributed than previously assumed. At least one representative encoding an RJL protein could be identified for each of the six major eukaryotic "supergroups" (Opisthokonta, Amoebozoa, Excavata, Archaeplastida, Chromalveolata, and Rhizaria) as well as for a species of Apusomonadida, a deep lineage that may not be specifically related to any of the recognized supergroups. Phylogenetic analyses do not support HGT of RJL genes between the major eukaryotic lineages, indicating that the RJL family was present in the last eukaryotic common ancestor and was lost several times over the course of eukaryotic evolution. Interestingly, RJL was lost from all taxa lacking flagellated cells and from a few lineages that build structurally unusual or reduced flagella, raising the intriguing possibility that RJL proteins are functionally associated with the flagellar apparatus. The RJL GTPase domain has been fused with the DnaJ domain on two separate occasions: in the Holozoa (before the split of Metazoa and choanoflagellates), giving rise to the previously known Rbj type of RJL with the DnaJ domain at the C-terminus, and independently in Alveolata resulting in novel proteins with the DnaJ domain at the N-terminus. These independent

  19. The RJL family of small GTPases is an ancient eukaryotic invention probably functionally associated with the flagellar apparatus.

    PubMed

    Elias, Marek; Archibald, John M

    2009-08-01

    A patchily distributed gene family is often taken as evidence for horizontal gene transfer (HGT) events, but it may also result solely from multiple gene losses. The RJL family of uncharacterised Ras-like GTPases was previously suggested to have undergone HGT events between protists and deuterostome metazoans, owing to the apparent absence of RJL in intermediate groups (Nepomuceno-Silva, J.L., de Melo, L.D., Mendonca, S.M., Paixao, J.C., Lopes, U.G., 2004. RJLs: a new family of Ras-related GTP-binding proteins. Gene 327, 221-232). We have reanalysed the phylogenetic distribution and phylogeny of the RJL family, taking advantage of the recent expansion of sequence data available from diverse eukaryotes. We found that RJL orthologs are much more widely distributed than previously assumed. At least one representative encoding an RJL protein could be identified for each of the six major eukaryotic "supergroups" (Opisthokonta, Amoebozoa, Excavata, Archaeplastida, Chromalveolata, and Rhizaria) as well as for a species of Apusomonadida, a deep lineage that may not be specifically related to any of the recognized supergroups. Phylogenetic analyses do not support HGT of RJL genes between the major eukaryotic lineages, indicating that the RJL family was present in the last eukaryotic common ancestor and was lost several times over the course of eukaryotic evolution. Interestingly, RJL was lost from all taxa lacking flagellated cells and from a few lineages that build structurally unusual or reduced flagella, raising the intriguing possibility that RJL proteins are functionally associated with the flagellar apparatus. The RJL GTPase domain has been fused with the DnaJ domain on two separate occasions: in the Holozoa (before the split of Metazoa and choanoflagellates), giving rise to the previously known Rbj type of RJL with the DnaJ domain at the C-terminus, and independently in Alveolata resulting in novel proteins with the DnaJ domain at the N-terminus. These independent

  20. A small family of sushi-class retrotransposon-derived genes in mammals and their relation to genomic imprinting.

    PubMed

    Youngson, Neil A; Kocialkowski, Sylvia; Peel, Nina; Ferguson-Smith, Anne C

    2005-10-01

    Ty3/gypsy retrotransposons are rare in mammalian genomes despite their abundance in invertebrate and other vertebrate classes. Here we identify a family of nine conserved mammalian genes with homology to Ty3/gypsy retrotransposons but which have lost their ability to autonomously retrotranspose. Of these, five map to the X chromosome while the remaining four are autosomal. Comparative phylogenetic analyses show them to have strongest homology to the sushi-ichi element from Fugu rubripes. Two of the autosomal gene members, Peg10 and Rtl1, are known to be imprinted, being expressed from the paternally inherited chromosome homologue. This suggests, consistent with the host-parasite response theory of the evolution of the imprinting mechanism, that parental-origin specific epigenetic control may be mediated by genomic "parasitic" elements such as these. Alternatively, these elements may preferentially integrate into regions that are differentially modified on the two homologous chromosomes such as imprinted domains and the X chromosome and acquire monoallelic expression. We assess the imprinting status of the remaining autosomal members of this family and show them to be biallelically expressed in embryo and placenta. Furthermore, the methylation status of Rtl1 was assayed throughout development and was found to resemble that of actively, silenced repetitive elements rather than imprinted sequences. This indicates that the ability to undergo genomic imprinting is not an inherent property of all members of this family of retroelements. Nonetheless, the conservation but functional divergence between the different members suggests that they have undergone positive selection and acquired distinct endogenous functions within their mammalian hosts.

  1. Economic Openness and the Marginalization of Small Family Farmers: Aligning Curriculum To Meet the Needs of Rural Adolescents in Brazil.

    ERIC Educational Resources Information Center

    Moore, Audrey-Marie Schuh

    Economic liberalization and the rise of global competition have increased the importance of agricultural, technical, and business skills for small farmers in Brazil. However, many rural farmers are unable to attend agricultural technical schools due to low educational attainment. The first section of this paper discusses the impact that…

  2. 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

  3. Mechanism for attenuation of DNA binding by MarR family transcriptional regulators by small molecule ligands.

    PubMed

    Perera, Inoka C; Lee, Yong-Hwan; Wilkinson, Steven P; Grove, Anne

    2009-07-31

    Members of the multiple antibiotic resistance regulator (MarR) family control gene expression in a variety of metabolic processes in bacteria and archaea. Hypothetical uricase regulator (HucR), which belongs to the ligand-responsive branch of the MarR family, regulates uricase expression in Deinococcus radiodurans by binding a shared promoter region between uricase and HucR genes. We show here that HucR responds only to urate and, to a lesser extent, to xanthine by attenuated DNA binding, compared to other intermediates of purine degradation. Using molecular-dynamics-guided mutational analysis, we identified the ligand-binding site in HucR. Electrophoretic mobility shift assays and intrinsic Trp fluorescence have identified W20 from the N-terminal helix and R80 from helix 3, which serves as a scaffold for the DNA recognition helix, as being essential for ligand binding. Using structural data combined with in silico and in vitro analyses, we propose a mechanism for the attenuation of DNA binding in which a conformational change initiated by charge repulsion due to a bound ligand propagates to DNA recognition helices. This mechanism may apply generally to MarR homologs that bind anionic phenolic ligands. PMID:19501097

  4. Multiple small "imaging" branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia?

    PubMed

    Bartsch, D K; Dietzel, K; Bargello, M; Matthaei, E; Kloeppel, G; Esposito, I; Heverhagen, J T; Gress, T M; Slater, E P; Langer, P

    2013-03-01

    Most screening programs for familial pancreatic cancer are currently based on endoscopic ultrasonography and/or magnetic resonance imaging (MRI). Cystic lesions, especially those suspicious for small intraductal pancreatic mucinous neoplasms (IPMNs) of the branch ducts, can be visualized in up to 40 % of individuals at risk, but their pathological importance in the setting of FPC is yet not well established. Individuals at risk from a prospective screening program for familial pancreatic cancer with small "imaging" IPMNs of the branch-duct type (BD-IPMN) who underwent pancreatic resection were analysed regarding clinico-pathological data and the locations of pancreatic lesions. Five of 125 individuals at risk who underwent screening had multiple small (size 2-10 mm) unicystic lesions and/or multicystic single lesions in the pancreatic body and tail suspicious for BD-IPMNs upon MRI imaging and decided to undergo surgical resection after interdisciplinary counselling, although none fulfilled the consensus criteria for IPMN resection. Histological examination revealed BD-IPMNs with low or moderate dysplasia of the gastric type in combination with multifocal PanIN2 and PanIN3 lesions in 4 individuals. The remaining patient had only tiny ductectasias in the pancreatic tail with multifocal PanIN 2 lesions in the entire gland and one PanIN3 lesion in the pancreatic head. Intriguingly, the location of the most dysplastic histological lesions (PanIN3) did not correspond to the preoperatively detected lesions and were not visible in preoperative imaging. In the setting of FPC, the presence of multiple small "imaging" BD-IPMNs may indicate the presence of high-grade PanIN lesions elsewhere in the pancreas.

  5. Small-Molecule Inhibitors That Target Protein–Protein Interactions in the RAD51 Family of Recombinases

    PubMed Central

    Scott, Duncan E; Coyne, Anthony G; Venkitaraman, Ashok; Blundell, Tom L; Abell, Chris; Hyvönen, Marko

    2015-01-01

    The development of small molecules that inhibit protein–protein interactions continues to be a challenge in chemical biology and drug discovery. Herein we report the development of indole-based fragments that bind in a shallow surface pocket of a humanised surrogate of RAD51. RAD51 is an ATP-dependent recombinase that plays a key role in the repair of double-strand DNA breaks. It both self-associates, forming filament structures with DNA, and interacts with the BRCA2 protein through a common “FxxA” tetrapeptide motif. We elaborated previously identified fragment hits that target the FxxA motif site and developed small-molecule inhibitors that are approximately 500-fold more potent than the initial fragments. The lead compounds were shown to compete with the BRCA2-derived Ac-FHTA-NH2 peptide and the self-association peptide of RAD51, but they had no effect on ATP binding. This study is the first reported elaboration of small-molecular-weight fragments against this challenging target. PMID:25470112

  6. Two novel members of the LhrC family of small RNAs in Listeria monocytogenes with overlapping regulatory functions but distinctive expression profiles.

    PubMed

    Mollerup, Maria Storm; Ross, Joseph Andrew; Helfer, Anne-Catherine; Meistrup, Kristine; Romby, Pascale; Kallipolitis, Birgitte Haahr

    2016-09-01

    Multicopy small RNAs (sRNAs) have gained recognition as an important feature of bacterial gene regulation. In the human pathogen Listeria monocytogenes, 5 homologous sRNAs, called LhrC1-5, control gene expression by base pairing to target mRNAs though 3 conserved UCCC motifs common to all 5 LhrCs. We show here that the sRNAs Rli22 and Rli33-1 are structurally and functionally related to LhrC1-5, expanding the LhrC family to 7 members, which makes it the largest multicopy sRNA family reported so far. Rli22 and Rli33-1 both contain 2 UCCC motifs important for post-transcriptional repression of 3 LhrC target genes. One such target, oppA, encodes a virulence-associated oligo-peptide binding protein. Like LhrC1-5, Rli22 and Rli33-1 employ their UCCC motifs to recognize the Shine-Dalgarno region of oppA mRNA and prevent formation of the ribosomal complex, demonstrating that the 7 sRNAs act in a functionally redundant manner. However, differential expression profiles of the sRNAs under infection-relevant conditions suggest that they might also possess non-overlapping functions. Collectively, this makes the LhrC family a unique case for studying the purpose of sRNA multiplicity in the context of bacterial virulence. PMID:27400116

  7. Differences in construction costs and chemical composition between deciduous and evergreen woody species are small as compared to differences among families.

    PubMed

    Villar, Rafael; Robleto, Jeannette Ruiz; De Jong, Yvonne; Poorter, Hendrik

    2006-08-01

    We tested to what extent differences in construction costs (CC) and chemical composition of woody species are attributed to leaf habit. Eight evergreen and eight deciduous species belonging to six families were selected to form eight phylogenetic independent contrasts (PICs). The plants were grown from seed in a glasshouse. Differences in leaf, stem and root CC between evergreen and deciduous species were minor, the proportion of variance explained by leaf habit generally being less than 6%. Surprisingly, differences in leaf chemical composition between deciduous and evergreen species were small as well. Variation in CC and chemical composition among families was substantial, the factor 'family' explaining 50-85% of variance. We therefore conclude that in this case, phylogeny is a more important factor than functional group. Leaves of the fast-growing species in this experiment showed high levels of minerals, organic acids, proteins and lipids, whereas leaves of the slow-growing species had higher concentrations of soluble phenolics, lignin as well as higher carbon/nitrogen (C/N) ratio. These relationships suggest a trade-off between growth and defence. In contrast, CC of leaves, stems, roots or whole plants showed no or only a weak correlation with relative growth rate (RGR). The C/N ratio of the leaves is an easily measured parameter that correlated strongly in a negative way with the RGR of the plants and reflected better the balance between investment in structure and physiological functioning than CC.

  8. Selective inhibition of the Kir2 family of inward rectifier potassium channels by a small molecule probe: the discovery, SAR and pharmacological characterization of ML133

    PubMed Central

    Wang, Hao-Ran; Wu, Meng; Yu, Haibo; Long, Shunyou; Stevens, Amy; Engers, Darren W.; Sackin, Henry; Daniels, J. Scott; Dawson, Eric S.; Hopkins, Corey R.; Lindsley, Craig W.; Li, Min; McManus, Owen B

    2011-01-01

    The Kir inward rectifying potassium channels have a broad tissue distribution and are implicated in a variety of functional roles. At least seven classes (Kir1 – Kir7) of structurally related inward rectifier potassium channels are known, and there are no selective small molecule tools to study their function. In an effort to develop selective Kir2.1 inhibitors, we performed a high-throughput screen (HTS) of more than 300,000 small molecules within the MLPCN for modulators of Kir2.1 function. Here we report one potent Kir2.1 inhibitor, ML133, which inhibits Kir2.1 with IC50 of 1.8 μM at pH 7.4 and 290 nM at pH 8.5, but exhibits little selectivity against other members of Kir2.x family channels. However, ML133 has no effect on Kir1.1 (IC50 > 300 μM), and displays weak activity for Kir4.1 (76 μM) and Kir7.1 (33 μM), making ML133 the most selective small molecule inhibitor of the Kir family reported to date. Due to the high homology within the Kir family, the channels share a common design of a pore region flanked by two transmembrane domains, identification of site(s) critical for isoform specificity would be an important basis for future development of more specific and potent Kir inhibitors. Using chimeric channels between Kir2.1 and Kir1.1 and site-directed mutagenesis, we have identified D172 and I176 within M2 segment of Kir2.1 as molecular determinants critical for the potency of ML133 mediated inhibition. Double mutation of the corresponding residues of Kir1.1 to those of Kir2.1 (N171D and C175I) transplants ML133 inhibition to Kir1.1. Together, the combination of a potent, Kir2 family selective inhibitor and identification of molecular determinants for the specificity provides both a tool and a model system to enable further mechanistic studies of modulation of Kir2 inward rectifier potassium channels. PMID:21615117

  9. 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.

  10. 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

  11. The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer.

    PubMed

    Navarro, Alfons; Tejero, Rut; Viñolas, Nuria; Cordeiro, Anna; Marrades, Ramon M; Fuster, Dolors; Caritg, Oriol; Moises, Jorge; Muñoz, Carmen; Molins, Laureano; Ramirez, Josep; Monzo, Mariano

    2015-10-13

    The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression.

  12. Structural and functional diversity in the family of small heat shock proteins from the parasite Toxoplasma gondii.

    PubMed

    de Miguel, Natalia; Braun, Nathalie; Bepperling, Alexander; Kriehuber, Thomas; Kastenmüller, Andreas; Buchner, Johannes; Angel, Sergio O; Haslbeck, Martin

    2009-11-01

    Small heat shock proteins (sHsps) are ubiquitous molecular chaperones which prevent the nonspecific aggregation of non-native proteins. Five potential sHsps exist in the parasite Toxoplasma gondii. They are located in different intracellular compartments including mitochondria and are differentially expressed during the parasite's life cycle. Here, we analyzed the structural and functional properties of all five proteins. Interestingly, this first in vitro characterization of sHsps from protists showed that all T. gondii sHsps exhibit the characteristic properties of sHsps such as oligomeric structure and chaperone activity. However, differences in their quaternary structure and in their specific chaperone properties exist. On the structural level, the T. gondii sHsps can be divided in small (12-18 subunits) and large (24-32 subunits) oligomers. Furthermore, they differ in their interaction with non-native proteins. While some bind substrates tightly, others interact more transiently. The chaperone activity of the three more mono-disperse T. gondii sHsps is regulated by temperature with a decrease in temperature leading to the activation of chaperone activity, suggesting an adaption to specific steps of the parasite's life cycle.

  13. The production of Multiple Small Peptaibol Families by Single 14-Module Peptide Synthetases in Trichoderma/Hypocrea

    SciTech Connect

    Degenkolb, Thomas; Aghchehb, Razieh Karimi; Dieckmann, Ralf; Neuhof, Torsten; Baker, Scott E.; Druzhinina, Irina S.; Kubicek, Christian P.; Brückner, Hans; von Dohren, Hans

    2012-03-01

    The most common peptaibibiotic structures are 11-residue peptaibols found widely distributed in the genus Trichoderma/Hypocrea. Frequently associated are 14-residue peptaibols sharing partial sequence identity. Genome sequencing projects of 3 Trichoderma strains of the major clades reveal the presence of up to 3 types of nonribosomal peptide synthetases with 7, 14, or 18-20 amino acid adding modules. We here provide evidence that the 14-module NRPS type found in T. virens, T. reesei (teleomorph Hypocrea jecorina) and T. atroviride produces both 11- and 14- residue peptaibols based on the disruption of the respective NRPS gene of T. reesei, and bioinformatic analysis of their amino acid activating domains and modules. The structures of these peptides may be predicted from the gene structures and have been confirmed by analysis of families of 11- and 14-residue peptaibols from the strain 618, termed hypojecorins A (23 sequences determined, 4 new) and B (3 new sequences), and the recently established trichovirins A from T. virens. The distribution of 11- and 14-residue products is strain-specific and depends on growth conditions as well. Possible mechanisms of module skipping are discussed.

  14. The PIM family of oncoproteins: small kinases with huge implications in myeloid leukemogenesis and as therapeutic targets.

    PubMed

    Saurabh, Kumar; Scherzer, Michael T; Shah, Parag P; Mims, Alice S; Lockwood, William W; Kraft, Andrew S; Beverly, Levi J

    2014-09-30

    PIM kinases are a family of serine/threonine kinases involved in cell survival and proliferation. There is significant structural similarity between the three PIM kinases (PIM1, PIM2 and PIM3) and only few amino acid differences. Although, several studies have specifically monitored the role of PIM1 in tumorigenesis, much less is known about PIM2 and PIM3. Therefore, in this study we have used in vitro cell culture models and in vivo bone marrow infection/transplantation to assess the comparative signaling and oncogenic potential of each of the three PIM kinases. All three PIM kinases were able to protect FL5.12 cells from IL3 withdrawal induced death. Interestingly, the downstream signaling cascades were indistinguishable between the three kinases. Transplantation of murine bone marrow co-expressing MYC and PIM1, PIM2 or PIM3 caused rapid and uniformly lethal myeloid leukemia. De-induction of MYC 18 days following transplantation significantly increased the survival of mice, even with continual expression of PIM kinases. Alternatively, mice treated at the pre-leukemic stage with a PIM kinase inhibitor increased the lifespan of the mice, even with continual expression of the MYC transgene. These data demonstrate the role of PIM kinases in driving myeloid leukemia, and as candidate molecules for therapy against human malignancies. PMID:25238262

  15. [Cadasil and other hereditary small vessel diseases of the brain--increasingly diagnosed conditions underlying familial ischaemic stroke and dementia].

    PubMed

    Gunda, Bence; Chabriat, Hugues; Bereczki, Dániel

    2011-03-30

    CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) has recently gained great interest in vascular neurology as the most common heritable cause of stroke and vascular dementia in adults. This autosomal dominant small vessel disease of the brain--unlike the sporadic, hypertensive form--appears already in adult midlife in the absence of vascular risk factors with ischemic episodes and progressive dementia, its first manifestation can be migraine with aura, and is often associated with psychiatric disturbances. The magnetic resonance imaging (MRI) changes showing a characteristic pattern may precede symptoms by more than a decade. The identification of the mutation of the NOTCH 3 gene responsible for the disorder encoding a transmembrane receptor of vascular smooth muscle cells - has given great impetus on research to understand the molecular and vascular pathogenesis of the disease. The special importance of this latter lies in the fact that CADASIL provides a pure genetic model for subcortical cerebral ischemia and vascular dementia without the confounding factors of comorbidities and advanced age. Thus insights into CADASIL may help us better understand the more common sporadic forms as well. Moreover CADASIL is one of the best studied examples of secondary migraine. Currently we have far less knowledge on other forms of hereditary small vessel disease of the brain such as CARASIL, HERNS, CRV, HVR, PXE etc. Neurologists are becoming more and more familiar with CADASIL, and with the wider availability of MRI it is increasingly diagnosed. However the disorder is still probably underrecognised. This review aims to summarize our current knowledge on CADASIL with special emphasis on diagnostic and differential diagnostic points for the practising neurologist. PMID:21545006

  16. Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families

    PubMed Central

    Moldenhauer Minillo, Renata; Sobreira, Nara; de Fatima de Faria Soares, Maria; Jurgens, Julie; Ling, Hua; Hetrick, Kurt N.; Doheny, Kimberly F.; Valle, David; Brunoni, Decio; Alvarez Perez, Ana B.

    2014-01-01

    Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed. PMID:25565926

  17. Identification of small molecule agonists of human relaxin family receptor 1 (RXFP1) by utilizing a homogenous cell-based cAMP assay

    PubMed Central

    Chen, Catherine Z.; Southall, Noel; Xiao, Jingbo; Marugan, Juan J.; Ferrer, Marc; Hu, Xin; Jones, Raisa E.; Feng, Shu; Agoulnik, Irina U.

    2016-01-01

    The relaxin hormone is involved in a variety of biological functions including female reproduction and parturition, regulation of cardiovascular, renal, pulmonary, and hepatic functions. It regulates extracellular matrix remodeling, cell invasiveness, proliferation, differentiation, and overall tissue homeostasis. The G protein-coupled receptor (GPCR) RXFP1, relaxin family receptor 1, is a cognate relaxin receptor that mainly signals through cyclic AMP second messenger. While agonists of the receptor could have a wide range of pharmacological utility, up to date, there are no reported small molecule agonists for relaxin receptors. Here, we report the development of quantitative high-throughput platform for RXFP1 agonist screen based on homogenous cell-based HTRF cAMP assay technology. Two small molecules of similar structure were independently identified from a screen of more than 365,677 compounds. Neither compound showed activity in a counter screen with HEK293T cells transfected with an unrelated GPCR vasopressin 1b receptor. These small molecule agonists also demonstrated selectivity against the RXFP2 receptor, providing a basis for future medicinal chemistry optimization of selective relaxin receptor agonists. PMID:23212924

  18. 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.

  19. 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,…

  20. The bldC Developmental Locus of Streptomyces coelicolor Encodes a Member of a Family of Small DNA-Binding Proteins Related to the DNA-Binding Domains of the MerR Family

    PubMed Central

    Hunt, Alison C.; Servín-González, Luis; Kelemen, Gabriella H.; Buttner, Mark J.

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed ΔbldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although ΔbldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein. PMID:15629942

  1. 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

  2. The VP3 factor from viruses of Birnaviridae family suppresses RNA silencing by binding both long and small RNA duplexes.

    PubMed

    Valli, Adrian; Busnadiego, Idoia; Maliogka, Varvara; Ferrero, Diego; Castón, José R; Rodríguez, José Francisco; García, Juan Antonio

    2012-01-01

    RNA silencing is directly involved in antiviral defense in a wide variety of eukaryotic organisms, including plants, fungi, invertebrates, and presumably vertebrate animals. The study of RNA silencing-mediated antiviral defences in vertebrates is hampered by the overlap with other antiviral mechanisms; thus, heterologous systems are often used to study the interplay between RNA silencing and vertebrate-infecting viruses. In this report we show that the VP3 protein of the avian birnavirus Infectious bursal disease virus (IBDV) displays, in addition to its capacity to bind long double-stranded RNA, the ability to interact with double-stranded small RNA molecules. We also demonstrate that IBDV VP3 prevents the silencing mediated degradation of a reporter mRNA, and that this silencing suppression activity depends on its RNA binding ability. Furthermore, we find that the anti-silencing activity of IBDV VP3 is shared with the homologous proteins expressed by both insect- and fish-infecting birnaviruses. Finally, we show that IBDV VP3 can functionally replace the well-characterized HCPro silencing suppressor of Plum pox virus, a potyvirus that is unable to infect plants in the absence of an active silencing suppressor. Altogether, our results support the idea that VP3 protects the viral genome from host sentinels, including those of the RNA silencing machinery.

  3. Rem2, a member of the RGK family of small GTPases, is enriched in nuclei of the basal ganglia

    PubMed Central

    Liput, Daniel J.; Lu, Van B.; Davis, Margaret I.; Puhl, Henry L.; Ikeda, Stephen R.

    2016-01-01

    Rem2 is a member of the RGK subfamily of RAS small GTPases. Rem2 inhibits high voltage activated calcium channels, is involved in synaptogenesis, and regulates dendritic morphology. Rem2 is the primary RGK protein expressed in the nervous system, but to date, the precise expression patterns of this protein are unknown. In this study, we characterized Rem2 expression in the mouse nervous system. In the CNS, Rem2 mRNA was detected in all regions examined, but was enriched in the striatum. An antibody specific for Rem2 was validated using a Rem2 knockout mouse model and used to show abundant expression in striatonigral and striatopallidal medium spiny neurons but not in several interneuron populations. In the PNS, Rem2 was abundant in a subpopulation of neurons in the trigeminal and dorsal root ganglia, but was absent in sympathetic neurons of superior cervical ganglia. Under basal conditions, Rem2 was subject to post-translational phosphorylation, likely at multiple residues. Further, Rem2 mRNA and protein expression peaked at postnatal week two, which corresponds to the period of robust neuronal maturation in rodents. This study will be useful for elucidating the functions of Rem2 in basal ganglia physiology. PMID:27118437

  4. The VP3 Factor from Viruses of Birnaviridae Family Suppresses RNA Silencing by Binding Both Long and Small RNA Duplexes

    PubMed Central

    Maliogka, Varvara; Ferrero, Diego; Castón, José R.; Rodríguez, José Francisco; García, Juan Antonio

    2012-01-01

    RNA silencing is directly involved in antiviral defense in a wide variety of eukaryotic organisms, including plants, fungi, invertebrates, and presumably vertebrate animals. The study of RNA silencing-mediated antiviral defences in vertebrates is hampered by the overlap with other antiviral mechanisms; thus, heterologous systems are often used to study the interplay between RNA silencing and vertebrate-infecting viruses. In this report we show that the VP3 protein of the avian birnavirus Infectious bursal disease virus (IBDV) displays, in addition to its capacity to bind long double-stranded RNA, the ability to interact with double-stranded small RNA molecules. We also demonstrate that IBDV VP3 prevents the silencing mediated degradation of a reporter mRNA, and that this silencing suppression activity depends on its RNA binding ability. Furthermore, we find that the anti-silencing activity of IBDV VP3 is shared with the homologous proteins expressed by both insect- and fish-infecting birnaviruses. Finally, we show that IBDV VP3 can functionally replace the well-characterized HCPro silencing suppressor of Plum pox virus, a potyvirus that is unable to infect plants in the absence of an active silencing suppressor. Altogether, our results support the idea that VP3 protects the viral genome from host sentinels, including those of the RNA silencing machinery. PMID:23049903

  5. 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.

  6. An annotated catalogue of the gamasid mites associated with small mammals in Asiatic Russia. The family Laelapidae s. str. (Acari: Mesostigmata: Gamasina).

    PubMed

    Vinarski, Maxim V; Korallo-Vinarskaya, Natalia P

    2016-01-01

    Twenty-nine species of mites of the family Laelapidae s. str. have been recorded as associated with small mammals (rodents, insectivores) in Asiatic Russia (Siberia and the Russian Far East). These species belong to two subfamilies (Laelapinae, Myonyssinae) and six genera: Androlaelaps Berlese, 1903, Dipolaelaps Zemskaya & Piontkovskaya, 1960, Laelaps C.L. Koch, 1836, Hyperlaelaps Zakhvatkin, 1948, Myonyssus Tiraboschi, 1904, Oryctolaelaps Lange, 1955. A list of the species, with data on synonymy, geographic ranges, and relationships with mammal hosts is provided. Some considerations concerning patterns of distribution of the parasitic Laelaptidae of Asiatic Russia are presented as well as their classifications from the point of view of known host association records. PMID:27395087

  7. Expression of apoptosis regulatory proteins of the Bcl-2 family and p53 in primary resected non-small-cell lung cancer

    PubMed Central

    Borner, M M; Brousset, P; Pfanner-Meyer, B; Bacchi, M; Vonlanthen, S; Hotz, M A; Altermatt, H J; Schlaifer, D; Reed, J C; Betticher, D C

    1999-01-01

    Proteins of the Bcl-2 family as well as p53 are important regulators of apoptosis. Alterations in the expression of these proteins can contribute to the formation of cancer, as well as influence tumour response to chemo- and radiotherapy. We used antibodies specific for the human Bcl-2, Mcl-1, Bax, Bak and p53 proteins to examine the expression of these apoptosis-regulating genes in 49 archival specimens of patients with radically resected non-small-cell lung cancer (NSCLC). Tumour cells containing immunostaining for the antiapoptotic proteins Bcl-2 and Mcl-1 were present in 31% and 58% of the cases evaluated, respectively, whereas immunopositivity for the proapoptotic proteins Bax and Bak was found in 47% and 58% of the samples. p53 immunopositivity was detected in 61% of the samples. The expression of Bcl-2 and p53 and the expression of Mcl-1 and Bax showed a positive association (P= 0.02 and P= 0.06 respectively), whereas the expression of Bax was inversely related to p53 (P= 0.008). The expression of Bcl-2 had a negative influence on relapse-free survival in this population of primary resected NSCLC patients (P= 0.02). The expression of p53 and Bcl-2 was significantly associated with metastasis-free survival (P< 0.01). Only patients with p53-positive tumours developed metastases during the follow-up period. Our results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl-1, Bax and Bak in NSCLC. It can be expected that Bcl-2 family members have no straightforward impact on clinical outcome in this disease because their interactions in the regulation of apoptosis are complex. © 1999 Cancer Research Campaign PMID:10070896

  8. TSC1 controls distribution of actin fibers through its effect on function of Rho family of small GTPases and regulates cell migration and polarity.

    PubMed

    Ohsawa, Maki; Kobayashi, Toshiyuki; Okura, Hidehiro; Igarashi, Takashi; Mizuguchi, Masashi; Hino, Okio

    2013-01-01

    The tumor-suppressor genes TSC1 and TSC2 are mutated in tuberous sclerosis, an autosomal dominant multisystem disorder. The gene products of TSC1 and TSC2 form a protein complex that inhibits the signaling of the mammalian target of rapamycin complex1 (mTORC1) pathway. mTORC1 is a crucial molecule in the regulation of cell growth, proliferation and survival. When the TSC1/TSC2 complex is not functional, uncontrolled mTORC1 activity accelerates the cell cycle and triggers tumorigenesis. Recent studies have suggested that TSC1 and TSC2 also regulate the activities of Rac1 and Rho, members of the Rho family of small GTPases, and thereby influence the ensuing actin cytoskeletal organization at focal adhesions. However, how TSC1 contributes to the establishment of cell polarity is not well understood. Here, the relationship between TSC1 and the formation of the actin cytoskeleton was analyzed in stable TSC1-expressing cell lines originally established from a Tsc1-deficient mouse renal tumor cell line. Our analyses showed that cell proliferation and migration were suppressed when TSC1 was expressed. Rac1 activity in these cells was also decreased as was formation of lamellipodia and filopodia. Furthermore, the number of basal actin stress fibers was reduced; by contrast, apical actin fibers, originating at the level of the tight junction formed a network in TSC1-expressing cells. Treatment with Rho-kinase (ROCK) inhibitor diminished the number of apical actin fibers, but rapamycin had no effect. Thus, the actin fibers were regulated by the Rho-ROCK pathway independently of mTOR. In addition, apical actin fibers appeared in TSC1-deficient cells after inhibition of Rac1 activity. These results suggest that TSC1 regulates cell polarity-associated formation of actin fibers through the spatial regulation of Rho family of small GTPases.

  9. Rapidly expanding genetic diversity and host range of the Circoviridae viral family and other Rep encoding small circular ssDNA genomes

    PubMed Central

    Delwart, Eric; Li, Linlin

    2011-01-01

    The genomes of numerous circoviruses and distantly related circular DNA viruses encoding a rolling circle replication initiator protein (Rep) have been characterized from the tissues of mammals, fish, insects, and plants (geminivirus and nanovirus), human and animal feces, in an algae cell, and in diverse environmental samples. We review the genome organization, phylogenetic relationships and initial prevalence studies of cycloviruses, a proposed new genus in the Circoviridae family. Viral fossil rep sequences were also identified integrated on the chromosomes of mammals, frogs, lancelets, crustaceans, mites, gastropods, roundworms, placozoans, hydrozoans, protozoans, land plants, fungi, algae, and phytoplasma bacterias and their plasmids, reflecting their past host range. An ancient origin for viruses with rep-encoding single stranded small circular genomes, predating the diversification of eukaryotes, is discussed. The cellular hosts and pathogenicity of many recently described rep-containing circular genomes remain to be determined. Future studies of the virome of single cell and multi-cellular eukaryotes are likely to further extend the known diversity and host-range of small rep-containing circular viral genomes. PMID:22155583

  10. 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

  11. Suppression of Wnt signaling by the miR-29 family is mediated by demethylation of WIF-1 in non-small-cell lung cancer

    SciTech Connect

    Tan, Min; Wu, Junjie; Cai, Yong

    2013-09-06

    Highlights: •Dnmt3A and Dnmt3B are involved in the down-regulation of WIF-1 expression in non-small-cell lung cancer. •MiR-29 family members could restore WIF-1 expression through demethylation. •MiR-29s suppress Wnt/β-catenin signaling pathway and inhibit tumor growth. •The expression of miR-29a and miR-29b could be regulated partially in a positive feedback loop. -- Abstract: Wnt inhibitory factor-1 (WIF-1) silencing induced by promoter hypermethylation is a common mechanism of aberrant activation of the Wnt signaling pathway in non-small-cell lung cancer (NSCLC). However, the activity of regulators associated with the methylation of the WIF-1 gene remains unclear. Here, we investigated the role of three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) in the expression of WIF-1. The three DNMTs were up-regulated in NSCLC tumor tissues and suppression of DNMT3A and DNMT3B restored the expression of WIF-1 in NSCLC cells. The miR-29 family (miR-29a, -29b, and -29c), which negatively regulates DNMT3A and DNMT3B, was examined in association with the Wnt/β-catenin signaling pathway. A positive correlation between the expression of WIF-1 and that of MiR-29s was observed in NSCLC tissues. Methylation-specific PCR and Western blotting indicated that miR-29s positively regulate WIF-1 expression by inhibiting the methylation of its promoter. Furthermore, miR-29 overexpression downregulated β-catenin expression, inhibited cell proliferation and induced apoptosis. The expression of miR-29a and miR-29b was partially regulated by DNMT3A and DNMT3B in a positive feedback loop. Taken together, our findings show that miR-29s suppress the Wnt signaling pathway through demethylation of WIF-1 in NSCLC.

  12. 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

  13. 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.

  14. 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

  15. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    ClinicalTrials.gov

    2016-10-13

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  16. 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

  17. Deletion of the gene family of small chlorophyll-binding proteins (ScpABCDE) offsets C/N homeostasis in Synechocystis PCC 6803.

    PubMed

    Tibiletti, Tania; Hernández-Prieto, Miguel A; Matthijs, Hans C P; Niyogi, Krishna K; Funk, Christiane

    2016-04-01

    In the family of chlorophyll binding proteins, single helix small CAB-like proteins (SCPs) are found in all organisms performing oxygenic photosynthesis. Here, we investigated the function of these stress-inducible proteins in the cyanobacterium Synechocystis sp. PCC 6803. We compared physiological, proteome and transcriptome traits of a Photosystem I (PSI) deletion strain, which constitutively induces SCPs, and a PSI-less/ScpABCDE(-) without SCPs. The SCP mutant cells were larger in size, showed irregular thylakoid structure and differed in cell-surface morphology. Deletion of scp genes strongly affected the carbon (C) and nitrogen (N) balance, resulting in accumulation of carbohydrates and a decrease in N-rich compounds (proteins and chlorophyll). Data from transcriptomic and metabolomic experiments revealed a role of SCPs in the control of chlorophyll biosynthesis. Additionally, SCPs diminished formation of reactive oxygen species, thereby preventing damage within Photosystem II. We conclude that the lack of SCP-function to remove free chlorophyll under stress conditions has a large impact on the metabolism of the entire cell. PMID:26646103

  18. Avocado cellulase: nucleotide sequence of a putative full-length cDNA clone and evidence for a small gene family.

    PubMed

    Tucker, M L; Durbin, M L; Clegg, M T; Lewis, L N

    1987-05-01

    A cDNA library was prepared from ripe avocado fruit (Persea americana Mill. cv. Hass) and screened for clones hybridizing to a 600 bp cDNA clone (pAV5) coding for avocado fruit cellulase. This screening led to the isolation of a clone (pAV363) containing a 2021 nucleotide transcribed sequence and an approximately 150 nucleotide poly(A) tail. Hybridization of pAV363 to a northern blot shows that the length of the homologous message is approximately 2.2 kb. The nucleotide sequence of this putative full-length mRNA clone contains an open reading frame of 1482 nucleotides which codes for a polypeptide of 54.1 kD. The deduced amino acid composition compares favorably with the amino acid composition of native avocado cellulase determined by amino acid analysis. Southern blot analysis of Hind III and Eco RI endonuclease digested genomic DNA indicates a small family of cellulase genes.

  19. The p53 family member p73 modulates the proproliferative role of IGFBP3 in short children born small for gestational age.

    PubMed

    Marzano, Flaviana; Ventura, Annamaria; Caratozzolo, Mariano Francesco; Aiello, Italia; Mastropasqua, Francesca; Brunetti, Giacomina; Cavallo, Luciano; Sbisà, Elisabetta; Faienza, Maria Felicia; Tullo, Apollonia

    2015-08-01

    The regulation of insulin-like growth factor-binding protein 3 (IGFBP3) gene expression is complex, because it can be induced by agents that both stimulate and inhibit the proliferation. The principal aim of this study was to investigate whether p73, a member of the p53 gene family, has a role in the regulation of the IGFBP3 expression and whether this regulation occurs in a context of cell survival or death. We demonstrate that IGFBP3 is a direct TAp73α (the p73 isoform that contains the trans-activation domain) target gene and activates the expression of IGFBP3 in actively proliferating cells. As IGFBP3 plays a key role in regulating the growth hormone/insulin-like growth factor type 1 (GH/IGF1) axis, whose alterations in gene expression appear to have a role in the growth failure of children born small for gestational age (SGA), we measured the mRNA expression levels of p73 and IGFBP3 in a group of SGA children. We found that mRNA expression levels of p73 and IGFBP3 are significantly lower in SGA children compared with controls and, in particular, p73 mRNA expression is significantly lower in SGA children with respect to height. Our results shed light on the intricate GH/IGF pathway, suggesting p73 as a good biomarker of the clinical risk for SGA children to remain short in adulthood. PMID:26063735

  20. New Perspectives on the Rural Economy. Hearing on New Perspectives on the Rural Economy before the Subcommittee on Rural Economy and Family Farming of the Committee on Small Business. United States Senate, One Hundredth Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Small Business.

    Testimony and prepared statements presented at a hearing before the Senate Subcommittee on Rural Economy and Family Farming focused on the concerns of rural small business. Witnesses included Senators from Montana, Illinois, New York, Oklahoma, South Dakota, Wisconsin, Minnesota, and Iowa, and nine representatives of business, state government,…

  1. Differential expression of calcium-activated chloride channels (CLCA) gene family members in the small intestine of cystic fibrosis mouse models.

    PubMed

    Leverkoehne, Ina; Holle, Hannah; Anton, Friederike; Gruber, Achim D

    2006-08-01

    Members of the family of calcium-activated chloride channels (CLCA) have been implicated as modulators of the phenotype in cystic fibrosis (CF). Here, the expression levels of the murine mCLCA1, mCLCA2, mCLCA3 and mCLCA4 were quantified by real-time RT-PCR in the small intestines of CF (cftr (tm1Cam), cftr (TgH(neoim)1Hgu)) and wild type C57BL/6, BALB/c, DBA/2 and NMRI mice. Markedly different expression levels of all four CLCA homologs were observed between the different wild type strains. Expression of mCLCA1 and mCLCA4 was similar in CF versus wild type. In contrast, mCLCA3 mRNA copy numbers were increased up to threefold in all CF models. Immunohistochemical detection of mCLCA3 and PAS reactions on consecutive tissue sections identified a similar increase in mCLCA3 expressing goblet cells, suggesting that elevated mRNA copy numbers of mCLCA3 are due to goblet cell hyperplasia rather than transcriptional regulatory events. Increased mCLCA2 mRNA copy numbers, however, were considered more likely to be due to transcriptional upregulation. Changes in mRNA copy numbers were not associated with altered cell kinetics as determined by immunohistochemistry using antibodies to phospho-histone 3 and activated caspase-3. The results suggest that both mCLCA2 and mCLCA3 may act as modifiers of the intestinal phenotype in CF.

  2. 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.

  3. 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.

  4. [A 73-year-old woman with familial Parkinson's disease].

    PubMed

    Takanashi, M; Urabe, T; Ohta, S; Hamano, Y; Mori, H; Shirai, T; Kondo, T; Mizuno, Y

    1999-12-01

    We report a 73-year-old Japanese woman with familial Parkinson's disease. The patient was well until her 67 years of the age, when she noted rest tremor in her right hand. Soon after her gait became short stepped. She visited our clinic on October 6, 1992 when she was 68 years old. She was alert and well oriented without dementia. She showed masked face, small voice, small stepped gait, retropulsion, resting tremor in her right hand, rigidity in the neck, and bradykinesia. She was treated with 400 mg/day of levodopa-carbidopa, which improved her symptoms, however, she developed wearing off phenomenon 3 years after the initiation of levodopa treatment. On August 26, 1998, she developed abdominal pain, diarrhea, and vomiting. She was admitted to another hospital, where abdominal plain x-ray revealed an evidence of intestinal obstruction (ileus). She was treated with nasogastric suction and intravenous fluid. Her condition did not improve and she was transferred to our hospital on August 29, 1998. Her family history revealed no consanguineous marriage. She had two elder brothers and three elder sisters. One of her brothers had been diagnosed as Parkinson's disease. Her husband also suffered from Parkinson's disease, however, her parents apparently did not have Parkinson's disease. On admission, she appeared to be drowsy. Her blood pressure was 102/70 mmHg, body temperature 36.2 degrees C. The lungs were clear and no cardiac murmur was present. Abdomen was flat and bowel sound was audible. No abnormal mass was palpable. Neurologic examination revealed mild consciousness disturbance, masked face, and small voice. No motor paralysis was noted. Muscle tone was hypotonic. No abnormal involuntary movement was noted. Abnormal laboratory findings on admission were as follows; WBC 11,300/microliter, amylase 1,373 IU/l, CK 446 IU/l, BUN 50 mg/dl, creatinine 1.17 mg/dl, CRP 22.7 mg/ dl, Na 134 mEq/l, K 3.1 mEq/l, and Cl 81 mEq/l. A chest x-ray film revealed pneumonic shadows in

  5. 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.

  6. [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

  7. 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

  8. 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

  9. Changes in American Family Life

    ERIC Educational Resources Information Center

    Norton, Arthur J.; Glick, Paul C.

    1976-01-01

    This article attempts to provide a factual, historical perspective on the current family situation of American children. Demographic statistics from recent decades are given which show trends toward small family size, nuclear families, one-parent families, and a higher level of education among parents. (MS)

  10. The Australian Middle Class and Education: A Small-Scale Study of the School Choice Experience as Framed by "My School" within Inner City Families

    ERIC Educational Resources Information Center

    Rowe, Emma E.; Windle, Joel

    2012-01-01

    With the launch of the "My School" website in 2010, Australia became a relative latecomer to the publication of national school performance comparisons. This paper primarily seeks to explore the school choice experience as framed by "My School" website, for participating middle-class families. We will draw on Bourdieusian theory of cultural…

  11. 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.

  12. Vorticella Linnaeus, 1767 (Ciliophora, Oligohymenophora, Peritrichia) is a grade not a clade: redefinition of Vorticella and the families Vorticellidae and Astylozoidae using molecular characters derived from the gene coding for small subunit ribosomal RNA.

    PubMed

    Sun, Ping; Clamp, John; Xu, Dapeng; Kusuoka, Yasushi; Miao, Wei

    2012-01-01

    Recent phylogenetic analyses of the peritrich genus Vorticella have suggested that it might be paraphyletic, with one Vorticella species - Vorticella microstoma grouping with the swimming peritrichs Astylozoon and Opisthonecta in a distant clade. These results were based on very limited taxon sampling and thus could not be accepted as conclusive evidence for revising the generic classification. We tested paraphyly of the genus Vorticella by making a new analysis with a broad range of samples from three continents that yielded 52 new sequences of the gene coding for small subunit rRNA. Our results, together with the available sequences in Genbank, form a comprehensive set of data for the genus Vorticella. Analyses of these data showed that Vorticella microstoma morphotypes, Astylozoon, and Opisthonecta form a well-supported, monophyletic clade, that is distinct from and basal to the family Vorticellidae containing other species of Vorticella. Paraphyly of the genus Vorticella and family Vorticellidae was strongly confirmed by these results. Furthermore, the two clades of Vorticella identified by the SSU rRNA gene are so genetically diverse whereas the genetic distances within the one containing Vorticella microstoma morphotypes, Astylozoon, and Opisthonecta were so slight, which marked it as a separate family that must be defined by molecular characters in the absence of unifying morphological and morphogenetic characters. An emended characterization and status of the genus Vorticella, the families Vorticellidae and Astylozoidae are presented and discussed. PMID:21784703

  13. A tomato xylem sap protein represents a new family of small cysteine-rich proteins with structural similarity to lipid transfer proteins.

    PubMed

    Rep, Martijn; Dekker, Henk L; Vossen, Jack H; de Boer, Albert D; Houterman, Petra M; de Koster, Chris G; Cornelissen, Ben J C

    2003-01-16

    The coding sequence of a major xylem sap protein of tomato was identified with the aid of mass spectrometry. The protein, XSP10, represents a novel family of extracellular plant proteins with structural similarity to plant lipid transfer proteins. The XSP10 gene is constitutively expressed in roots and lower stems. The decline of XSP10 protein levels in tomato infected with a fungal vascular pathogen may reflect breakdown or modification by the pathogen.

  14. 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

  15. 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

  16. [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.

  17. 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

  18. Family dynamics in biblical times: Joseph as a family psychotherapist.

    PubMed

    Ben-Noun, Liubov Louba

    2003-06-01

    Families have existed for thousands of years and are the most enduring form of small social group. This article discusses the family of Jacob as described in the Bible, and analyses the dynamics of the family system, the relationships between family members and the ways in which they interact and respond to stressful events. Such events disrupted the equilibrium of the family and led to a severe crisis, but this was eventually resolved peacefully and family members were reconciled. The story of Joseph, Jacob's son, unfolds as possibly the earliest description of a psychotherapeutic intervention to resolve a long-standing family crisis.

  19. Crystallization and preliminary X-ray diffraction analysis of XAC1151, a small heat-shock protein from Xanthomonas axonopodis pv. citri belonging to the α-crystallin family

    SciTech Connect

    Hilario, Eduardo; Teixeira, Elaine Cristina; Pedroso, Gisele Audrei; Bertolini, Maria Célia; Medrano, Francisco Javier

    2006-05-01

    XAC1151, a small heat-shock protein from X. axonopodis pv. citri belonging to the α-crystallin family, was crystallized using the sitting-drop vapour-diffusion method in the presence of ammonium phosphate. X-ray diffraction data were collected to 1.65 Å resolution using a synchrotron-radiation source. The hspA gene (XAC1151) from Xanthomonas axonopodis pv. citri encodes a protein of 158 amino acids that belongs to the small heat-shock protein (sHSP) family of proteins. These proteins function as molecular chaperones by preventing protein aggregation. The protein was crystallized using the sitting-drop vapour-diffusion method in the presence of ammonium phosphate. X-ray diffraction data were collected to 1.65 Å resolution using a synchrotron-radiation source. The crystal belongs to the rhombohedral space group R3, with unit-cell parameters a = b = 128.7, c = 55.3 Å. The crystal structure was solved by molecular-replacement methods. Structure refinement is in progress.

  20. 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

  1. 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.

  2. Not Your Family Farm

    ERIC Educational Resources Information Center

    Tenopir, Carol; Baker, Gayle; Grogg, Jill E.

    2007-01-01

    The information industry continues to consolidate, just as agribusiness has consolidated and now dominates farming. Both the family farm and the small information company still exist but are becoming rarer in an age of mergers, acquisitions, and increased economies of scale. Small companies distinguish themselves by high quality, special themes,…

  3. 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.

  4. Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: Multiple allelic mutations of the IDUA gene in a small geographic area

    SciTech Connect

    Bach, G. ); Moskowitz, S.M.; Tieu, P.T.; Matynia, A.; Neufeld, E.F. )

    1993-08-01

    The mutations underlying Hurler syndrome (mucopolysaccharidosis IH) in Druze and Muslim Israeli Arab patients have been characterized. Four alleles were identified, using a combination of (a) PCR amplification of reverse-transcribed RNA or genomic DNA segments, (b) cycle sequencing of PCR products, and (c) restriction-enzyme analysis. One allele has two amino acid substitutions, Gly[sub 409][yields]Arg in exon 9 and Ter[yields]Cys in exon 14. The other three alleles have mutations in exon 2 (Tyr[sub 64][yields]Ter), exon 7 (Gln[sub 310][yields]Ter), or exon 8 (Thr[sub 366][yields]Pro). Transfection of mutagenized cDNAs into Cos-1 cells showed that two missense mutations, Thr[sub 366][yields]Pro and Ter[yields]Cys, permitted the expression of only trace amounts of [alpha]-L-iduronidase activity, whereas Gly[sub 409][yields]Arg permitted the expression of 60% as much enzyme as did the normal cDNA. The nonsense mutations were associated with abnormalities of RNA processing: (1) both a very low level of mRNA and skipping of exon 2 for Tyr[sub 64][yields]Ter and (2) utilization of a cryptic splice site for Gln[sub 310][yields]Ter. In all instances, the probands were found homozygous, and the parents heterozygous, for the mutant alleles, as anticipated from the consanguinity in each family. The two-mutation allele was identified in a family from Gaza; the other three alleles were found in seven families, five of them Druze, residing in a very small area of northern Israel. Since such clustering suggests a classic founder effect, the presence of three mutant alleles of the IDUA gene was unexpected. 28 refs., 4 figs., 3 tabs.

  5. 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 ...

  6. 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 ...

  7. 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 ...

  8. Structure, expression, and phylogenetic relationships of a family of ypt genes encoding small G-proteins in the green alga Volvox carteri.

    PubMed

    Fabry, S; Jacobsen, A; Huber, H; Palme, K; Schmitt, R

    1993-09-01

    In addition to the previously described gene yptV1 encoding a small G-protein we have now identified and sequenced four more ras-related ypt genes (yptV2-yptV5) from the green alga Volvox carteri. The four new genes encode polypeptides consisting of 203 to 217 amino-acid residues that contain the typical sequence elements (GTP-binding domains, effector domain) of the ypt/rab subgroup of the Ras superfamily. Comparison of the derived amino-acid sequences from the V. carteri ypt gene products and their Ypt homologs from other species revealed similarity values ranging from 60% to 85%, whereas intraspecies similarities were found to approach only 55%. The coding sequences are interrupted by 5-7 introns of variable size (70-1000 nucleotides) occupying different positions in the genes. Reverse-transcribed samples of stage-specific RNAs were PCR-amplified with primers specific to yptV1, yptV3, yptV4, and yptV5 to determine if yptV transcription might be restricted to either cell type or to a specific stage of the life cycle. These experiments demonstrated that each of these genes is expressed throughout the entire Volvox life cycle and in both the somatic and the reproductive cells of the alga. The transcription start sites of yptV1 and yptV5 were mapped by primer extension. Expression of recombinant yptV cDNA in E. coli yielded recombinant proteins that bound GTP specifically, demonstrating a property which is typical for small G-proteins. The derived YptV polypeptide sequences were used to group them into four distinct classes of Ras-like proteins. These are the first proteins of the Ras superfamily to be identified in a green alga. We discuss the possible role of the YptV-proteins in the intracellular vesicle transport of Volvox. PMID:8221932

  9. 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

  10. 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

  11. 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…

  12. 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…

  13. 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

  14. 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…

  15. 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…

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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);…

  2. 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…

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  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. The Family FIRO Model: The Integration of Group Theory and Family Theory.

    ERIC Educational Resources Information Center

    Colangelo, Nicholas; Doherty, William J.

    1988-01-01

    Presents the Family Fundamental Interpersonal Relations Orientation (Family FIRO) Model, an integration of small-group theory and family therapy. The model is offered as a framework for organizing family issues. Discusses three fundamental issues of human relatedness and their applicability to group dynamics. (Author/NB)

  10. 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)

  11. 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…

  12. 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…

  13. 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…

  14. 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...

  15. 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

  16. Family intervention for schizophrenia

    PubMed Central

    Pharoah, Fiona; Mari, Jair; Rathbone, John; Wong, Winson

    2014-01-01

    Background People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. Objectives To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. Search strategy We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). Selection criteria We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. Data collection and analysis We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). Main results This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of

  17. A functional interplay between the small GTPase Rab11a and mitochondria-shaping proteins regulates mitochondrial positioning and polarization of the actin cytoskeleton downstream of Src family kinases.

    PubMed

    Landry, Marie-Claude; Champagne, Claudia; Boulanger, Marie-Chloé; Jetté, Alexandra; Fuchs, Margit; Dziengelewski, Claire; Lavoie, Josée N

    2014-01-24

    It is believed that mitochondrial dynamics is coordinated with endosomal traffic rates during cytoskeletal remodeling, but the mechanisms involved are largely unknown. The adenovirus early region 4 ORF4 protein (E4orf4) subverts signaling by Src family kinases (SFK) to perturb cellular morphology, membrane traffic, and organellar dynamics and to trigger cell death. Using E4orf4 as a model, we uncovered a functional connection between mitochondria-shaping proteins and the small GTPase Rab11a, a key regulator of polarized transport via recycling endosomes. We found that E4orf4 induced dramatic changes in the morphology of mitochondria along with their mobilization at the vicinity of a polarized actin network typifying E4orf4 action, in a manner controlled by SFK and Rab11a. Mitochondrial remodeling was associated with increased proximity between Rab11a and mitochondrial membranes, changes in fusion-fission dynamics, and mitochondrial relocalization of the fission factor dynamin-related protein 1 (Drp1), which was regulated by the Rab11a effector protein FIP1/RCP. Knockdown of FIP1/RCP or inhibition of Drp1 markedly impaired mitochondrial remodeling and actin assembly, involving Rab11a-mediated mitochondrial dynamics in E4orf4-induced signaling. A similar mobilization of mitochondria near actin-rich structures was mediated by Rab11 and Drp1 in viral Src-transformed cells and contributed to the biogenesis of podosome rosettes. These findings suggest a role for Rab11a in the trafficking of Drp1 to mitochondria upon SFK activation and unravel a novel functional interplay between Rab11a and mitochondria during reshaping of the cell cytoskeleton, which would facilitate mitochondria redistribution near energy-requiring actin-rich structures.

  18. Crucial Role of Rapgef2 and Rapgef6, a Family of Guanine Nucleotide Exchange Factors for Rap1 Small GTPase, in Formation of Apical Surface Adherens Junctions and Neural Progenitor Development in the Mouse Cerebral Cortex123

    PubMed Central

    Maeta, Kazuhiro; Edamatsu, Hironori; Nishihara, Kaori; Ikutomo, Junji; Bilasy, Shymaa E.

    2016-01-01

    Abstract Cerebral neocortex development in mammals requires highly orchestrated events involving proliferation, differentiation, and migration of neural progenitors and neurons. Rapgef2 and Rapgef6 constitute a unique family of guanine nucleotide exchange factors for Rap1 small GTPase, which is known to play crucial roles in migration of postmitotic neurons. We previously reported that conditional knockout of Rapgef2 in dorsal telencephalon (Rapgef2-cKO) resulted in the formation of an ectopic cortical mass (ECM) resembling that of subcortical band heterotopia. Here we show that double knockout of Rapgef6 in Rapgef2-cKO mice (Rapgef2/6-dKO) results in marked enlargement of the ECM. While Rapgef2-cKO affects late-born neurons only, Rapgef2/6-dKO affects both early-born and late-born neurons. The Rapgef2-cKO cortex at embryonic day (E) 15.5, and the Rapgef2/6-dKO cortex at E13.5 and E15.5 show disruption of the adherens junctions (AJs) on the apical surface, detachment of radial glial cells (RGCs) from the apical surface and disorganization of the radial glial fiber system, which are accompanied by aberrant distribution of RGCs and intermediate progenitors, normally located in the ventricular zone and the subventricular zone, respectively, over the entire cerebral cortex. Moreover, intrauterine transduction of Cre recombinase into the Rapgef2flox/flox brains also results in the apical surface AJ disruption and the RGC detachment from the apical surface, both of which are effectively suppressed by cotransduction of the constitutively active Rap1 mutant Rap1G12V. These results demonstrate a cell-autonomous role of the Rapgef2/6-Rap1 pathway in maintaining the apical surface AJ structures, which is necessary for the proper development of neural progenitor cells. PMID:27390776

  19. A Functional Interplay between the Small GTPase Rab11a and Mitochondria-shaping Proteins Regulates Mitochondrial Positioning and Polarization of the Actin Cytoskeleton Downstream of Src Family Kinases*

    PubMed Central

    Landry, Marie-Claude; Champagne, Claudia; Boulanger, Marie-Chloé; Jetté, Alexandra; Fuchs, Margit; Dziengelewski, Claire; Lavoie, Josée N.

    2014-01-01

    It is believed that mitochondrial dynamics is coordinated with endosomal traffic rates during cytoskeletal remodeling, but the mechanisms involved are largely unknown. The adenovirus early region 4 ORF4 protein (E4orf4) subverts signaling by Src family kinases (SFK) to perturb cellular morphology, membrane traffic, and organellar dynamics and to trigger cell death. Using E4orf4 as a model, we uncovered a functional connection between mitochondria-shaping proteins and the small GTPase Rab11a, a key regulator of polarized transport via recycling endosomes. We found that E4orf4 induced dramatic changes in the morphology of mitochondria along with their mobilization at the vicinity of a polarized actin network typifying E4orf4 action, in a manner controlled by SFK and Rab11a. Mitochondrial remodeling was associated with increased proximity between Rab11a and mitochondrial membranes, changes in fusion-fission dynamics, and mitochondrial relocalization of the fission factor dynamin-related protein 1 (Drp1), which was regulated by the Rab11a effector protein FIP1/RCP. Knockdown of FIP1/RCP or inhibition of Drp1 markedly impaired mitochondrial remodeling and actin assembly, involving Rab11a-mediated mitochondrial dynamics in E4orf4-induced signaling. A similar mobilization of mitochondria near actin-rich structures was mediated by Rab11 and Drp1 in viral Src-transformed cells and contributed to the biogenesis of podosome rosettes. These findings suggest a role for Rab11a in the trafficking of Drp1 to mitochondria upon SFK activation and unravel a novel functional interplay between Rab11a and mitochondria during reshaping of the cell cytoskeleton, which would facilitate mitochondria redistribution near energy-requiring actin-rich structures. PMID:24302731

  20. 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

  1. 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…

  2. 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.

  3. 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

  4. 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 ...

  5. 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

  6. 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 ...

  7. 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)

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Familial pancreatic cancer.

    PubMed

    Klein, A P; Hruban, R H; Brune, K A; Petersen, G M; Goggins, M

    2001-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.

  15. 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

  16. 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

  17. 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

  18. Overcoming resistance to family-witnessed resuscitation.

    PubMed

    Jordahl, Erica; Hyde, Yolanda M; Kautz, Donald D

    2015-01-01

    Giving family members the option of being present during resuscitation has been shown to be beneficial for both family and staff. However, only a small percentage of intensive care units have policies promoting family-witnessed resuscitation. This article reviews current research showing the benefits of family-witnessed resuscitation, outlines how to successfully integrate a family facilitator during resuscitation, and includes research that has been effective in changing the prevailing attitudes of staff. The authors also argue for the resuscitation team to practice ethical and cultural humility when involving family members so that all resuscitation efforts are a success, whether the patient lives or dies.

  19. Family size and economic welfare.

    PubMed

    Espenshade, T J; Kamenske, G; Turchi, B A

    1983-01-01

    Using data from the 1972-1973 Consumer Expenditure Survey, this article examines the effect of variations in family size on such measures of family economic well-being as levels and patterns of spending, earnings and employment, public assistance and the quantity and quality of housing. In general, although overall income rises somewhat with family size, an increase in the number of children appears to reduce the family's standard of living, especially in young families with small children. Current consumption increases as the number of children increases: families with 4 or more children in which the household head is under the age of 35 and has had more than 12 years of education tend to spend 40% more than childless couples of similar age and educational level. Despite the increased spending, per capita consumption falls for all age and education categories. Larger families devote more of their income to necessities and less to luxuries. Among young couples in which the household head has had 9 to 12 years of education, the proportion of income used to buy food rises from 15% if there are no children present to 25% if there are 4 or more. The proportion of food expenditures devoted to meals eaten out also falls steadily as the number of children rises. Although husband's earnings rise with increase in family size, there is a pronounced decline in wife's earnings, particularly in young families that have children under the age of 4. Overall, as the number of children grows, families spend a larger share of their income on current consumption, and per capita income declines. The % of families receiving welfare or food stamps tends to go up as the number of children increases, particularly among younger couples with less education. When the quantity and quality of housing are examined, the average number of rooms in the family dwelling is found to increase with family size.

  20. 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.

  1. 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)

  2. 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.

  3. 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.

  4. 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

  5. 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…

  6. 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

  7. 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

  8. 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

  9. 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: " ...

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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…

  16. 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

  17. 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

  18. Small Wins.

    ERIC Educational Resources Information Center

    Rhatigan, James J.; Schuh, John H.

    2003-01-01

    Examines how it easy for people to overlook small successes when they are overwhelmed by and preoccupied with large projects and goals. Explores the concept of "small wins" in organizational theory, which have the potential to become a prominent part of institutional culture and impact organizational behavior and change. (GCP)

  19. Small Cultures.

    ERIC Educational Resources Information Center

    Holliday, Adrian

    1999-01-01

    Presents a notion of small culture as an alternative to what has become the default notion of large culture in applied linguistics, social science, and popular usage. A small-culture view of English-language curriculum settings reveals mismatches between professional-academic and organizational cultures at the mezzo level of the institution. (VWL)

  20. Familial Idiopathic Cranial Neuropathy in a Chinese Family.

    PubMed

    Zhang, Li; Liang, Jianfeng; Yu, Yanbing

    2016-01-01

    Cranial neuropathy is usually idiopathic and familial cases are uncommon. We describe a family with 5 members with cranial neuropathy over 3 generations. All affected patients were women, indicating an X-linked dominant or an autosomal dominant mode of inheritance. Our cases and a review of the literature suggest that familial idiopathic cranial neuropathy is a rare condition which may be related to autosomal dominant vascular disorders (e.g. vascular tortuosity, sclerosis, elongation or extension), small posterior cranial fossas, anatomical variations of the posterior circulation, hypersensitivity of cranial nerves and other abnormalities. Moreover, microvascular decompression is the treatment of choice because vascular compression is the main factor in the pathogenesis. To the best of our knowledge, this is the first report of familial cranial neuropathy in China. PMID:27161475

  1. 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

  2. Multigene families in African swine fever virus: family 360.

    PubMed Central

    González, A; Calvo, V; Almazán, F; Almendral, J M; Ramírez, J C; de la Vega, I; Blasco, R; Viñuela, E

    1990-01-01

    A group of cross-hybridizing DNA segments contained within the restriction fragments RK', RL, RJ, and RD' of African swine fever virus DNA were mapped and sequenced. Analysis of these sequences revealed the presence of a family of homologous open reading frames in regions close to the DNA ends. The whole family is composed of six open reading frames with an average length of 360 coding triplets (multigene family 360), four of which are located in the left part of the genome and two of which are in the right terminal EcoRI fragment. In close proximity to the right terminal inverted repeat, we found an additional small open reading frame which was homologous to the 5'-terminal portion of the other open reading frames, suggesting that most of that open reading frame has been deleted. These repeated sequences account for the previously described inverted internal repetitions (J.M. Sogo, J.M. Almendral, A. Talavera, and E. Viñuela, Virology 133:271-275, 1984). Most of the genes of multigene family 360 are transcribed in African swine fever virus-infected cells. A comparison of the predicted protein sequences of family 360 indicated that several residues are conserved, suggesting that an overall structure is maintained for every member of the family. The transcription direction of each open reading frame, as well as the evolutionary relationships among the genes, suggests that the family originated by gene duplication and translocation of sequences between the DNA ends. Images PMID:2325203

  3. 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. ...

  4. The Family Hero in Black Alcoholism Families.

    ERIC Educational Resources Information Center

    Brisbane, Francis L.

    1989-01-01

    Uses data from 20 case studies of Black adult female children of alcoholic parents to discuss Family Hero role often assumed by oldest or only female child in Black alcoholism families. Explains how female-dominated survival role of Family Hero in Black families is significantly more related to racial and cultural factors than numbers alone may…

  5. Integrating Family Resilience and Family Stress Theory.

    ERIC Educational Resources Information Center

    Patterson, Joan M.

    2002-01-01

    The construct, family resilience, is defined differently by practitioners and researchers. This study tries to clarify the concept of family resilience. The foundation is family stress and coping theory, particularly the stress models that emphasize adaptation processes in families exposed to major adversities. (JDM)

  6. Whole Family: Whole Child. Broken Family.

    ERIC Educational Resources Information Center

    DeVaul, Sue; Davis, John U.

    A literature review on the family environments of gifted students found that gifted children are more likely to be living in intact families than in divorced families. Children of single parents were more likely to be low-achieving, tardy, absent, truant, discipline problems, suspended, expelled, and dropouts than students in two-parent families.…

  7. Final Evaluation Report: Family to Family Program.

    ERIC Educational Resources Information Center

    Ramey, Luellen; Meyer, David P.

    This evaluation report of the Family to Family Program assesses parental attitudes towards their Family to Family experience and the functioning of their emotionally impaired children. It reviews issues of goal achievement; the impact on the targeted problem; service population demographics; and sustainability. Related topics include…

  8. Family Psychology and Family Therapy in Japan.

    ERIC Educational Resources Information Center

    Kameguchi, Kenji; Murphy-Shigematsu, Stephen

    2001-01-01

    Reviews the development of family psychology and family therapy in Japan, tracing the origins of these movements, explaining how these fields were activated by the problem of school refusal, and describing an approach to family therapy that has been developed to work with families confronting this problem, as well as preventive programs of family…

  9. Reclaiming Family Privilege

    ERIC Educational Resources Information Center

    Seita, John

    2012-01-01

    The pull for family is strong, almost primeval, most likely it is evolutionary, and for those lacking the benefit of family or Family Privilege, the loss of family is painful and profoundly sad. Young people who struggle to cope without stable family connections are profoundly aware of their lack of "Family Privilege." In this article, the author…

  10. The Impact of Deinstitutionalization on Family Contact.

    ERIC Educational Resources Information Center

    Spreat, Scott; Conroy, James W.

    2002-01-01

    Indices of family contact were reviewed across four cohorts of persons with mental retardation (n=151) who were transferred from a large public institution to small supported living arrangements. Family contact increased subsequent to community placement and these increased levels of contact were maintained for as long as four years. (Contains…

  11. Teaching English to Refugees: A Family Model.

    ERIC Educational Resources Information Center

    Andre, Elise; Brown, Dorothy S.

    The instructional program in English as a second language (ESL) followed by a family of 12 Hmong refugees in a small midwestern town is described. Eight of the younger members of the family met for one hour three times each week. Instruction was under the guidance of two teachers, thus allowing for individual help. Other volunteers assisted from…

  12. 76 FR 39115 - Notice of Proposed Information Collection: Transformation Initiative Family Self-Sufficiency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ... Family Self-Sufficiency Demonstration Small Grants. Description of the need for information and proposed... URBAN DEVELOPMENT Notice of Proposed Information Collection: Transformation Initiative Family Self-Sufficiency Demonstration Small Grants AGENCY: Office of Policy Development and Research, HUD. ACTION:...

  13. A Lebanese family with autosomal recessive oculo-auriculo-vertebral (OAV) spectrum and review of the literature: is OAV a genetically heterogeneous disorder?

    PubMed Central

    Farra, Chantal; Yunis, Khaled; Yazbeck, Nadine; Majdalani, Marianne; Charafeddine, Lama; Wakim, Rima; Awwad, Johnny

    2011-01-01

    Oculo-auriculo-vertebral (OAV) spectrum summarizes a continuum of ocular, auricular, and vertebral anomalies. Goldenhar syndrome is a variant of this spectrum and is characterized by pre-auricular skin tags, microtia, facial asymmetry, ocular abnormalities, and vertebral anomalies of different sizes and shapes. Most cases are thought to be sporadic. However, a few families were reported to have an autosomal recessive inheritance and other families’ presentation of the syndrome strongly supported an autosomal dominant inheritance. We report OAV in a female infant presenting with tracheomalacia, diaphragmatic hernia, encephalomeningocele, sacral neural tube defect, and cardiac defect and her brother having no more than dysmorphic features. The mode of inheritance in this family supports an autosomal recessive inheritance where the transmission was from normal first-degree consanguineous parents to one of the sons and to the daughter. This report further broadens the clinical presentation and symptoms of OAV and supports the hypothesis advancing OAV as a genetically heterogeneous disorder. PMID:23776370

  14. Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses.

    PubMed

    Fernandez, V; Hommel, M; Chen, Q; Hagblom, P; Wahlgren, M

    1999-11-15

    Disease severity in Plasmodium falciparum infections is a direct consequence of the parasite's efficient evasion of the defense mechanisms of the human host. To date, one parasite-derived molecule, the antigenically variant adhesin P. falciparum erythrocyte membrane protein 1 (PfEMP1), is known to be transported to the infected erythrocyte (pRBC) surface, where it mediates binding to different host receptors. Here we report that multiple additional proteins are expressed by the parasite at the pRBC surface, including a large cluster of clonally variant antigens of 30-45 kD. We have found these antigens to be identical to the rifins, predicted polypeptides encoded by the rif multigene family. These parasite products, formerly called rosettins after their identification in rosetting parasites, are prominently expressed by fresh isolates of P. falciparum. Rifins are immunogenic in natural infections and strain-specifically recognized by human immune sera in immunoprecipitation of surface-labeled pRBC extracts. Furthermore, human immune sera agglutinate pRBCs digested with trypsin at conditions such that radioiodinated PfEMP1 polypeptides are not detected but rifins are detected, suggesting the presence of epitopes in rifins targeted by agglutinating antibodies. When analyzed by two-dimensional electrophoresis, the rifins resolved into several isoforms in the pI range of 5.5-6.5, indicating molecular microheterogeneity, an additional potential novel source of antigenic diversity in P. falciparum. Prominent polypeptides of 20, 22, 76-80, 140, and 170 kD were also detected on the surfaces of pRBCs bearing in vitro-propagated or field-isolated parasites. In this report, we describe the rifins, the second family of clonally variant antigens known to be displayed by P. falciparum on the surface of the infected erythrocyte.

  15. Numerical limits in donor conception regimes: genetic links and 'extended family' in the era of identity disclosure.

    PubMed

    Millbank, Jenni

    2014-01-01

    This article critically examines the setting of limits on the number of children or family groups that may be formed with a single donor in assisted conception regimes. Originally, under conditions of anonymity, numerical limits were said to contain the risk of inadvertent consanguinity between offspring who would not know, and could not know, that they were genetic half siblings, and also between donor and offspring. The increasing embrace of identity disclosure regimes has led to calls for stricter numerical limits based on the purported harm of being exposed to 'too many' genetic relatives in the future. This article asks: how many is too many? And how do we know? The UK and Australian positions are examined, and placed alongside a discussion of qualitative research involving interviews with twenty parents of donor conceived children.

  16. Family and family therapy in Russia.

    PubMed

    Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

    2012-04-01

    This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized. PMID:22515460

  17. Family and family therapy in Russia.

    PubMed

    Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

    2012-04-01

    This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized.

  18. The Changing Family Structure.

    ERIC Educational Resources Information Center

    Bernard van Leer Foundation Newsletter, 1993

    1993-01-01

    This newsletter issue contains feature articles and short reports on how and why family structures are undergoing substantial change in many parts of the world. These articles include: (1) "The Changing Family Structure," a review of how families are changing and why; (2) "Peru: Families in the Andes"; (3) "Thailand: Families of the Garbage Dump";…

  19. Family Literacy and ESL.

    ERIC Educational Resources Information Center

    Red, David L.

    2003-01-01

    Discusses family literacy and English as a Second Language, focusing on types of family literacy programs, issues in family literacy, and future directions in family literacy. Highlights one program and lists the components of three approaches to family literacy: intervention prevention, multiple literacies, and social change. (Author/VWL)

  20. Family Reading Night

    ERIC Educational Resources Information Center

    Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

    2007-01-01

    This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

  1. Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246

    SciTech Connect

    Levy, E. N.; Aksentijevich, I.; Pras, E.

    1996-03-01

    This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbruck formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM). 41 refs., 3 figs., 5 tabs.

  2. Mutations of the AMH type II receptor in two extended families with persistent Müllerian duct syndrome: lack of phenotype/genotype correlation.

    PubMed

    Abduljabbar, Mohammad; Taheini, Khalid; Picard, Jean-Yves; Cate, Richard L; Josso, Nathalie

    2012-01-01

    Our goal was to compare phenotype and genotype in two extended Middle-Eastern families affected by persistent Müllerian duct syndrome due to mutations of the type II anti-Müllerian hormone receptor (AMHR-II). The first, consanguineous, family consisted of 6 boys and 2 girls, the second consisted of 4 girls and 2 boys. In family I, 4 boys and 1 girl were homozygous for a stop mutation in the 9th exon of AMHR-II, removing part of the intracellular domain of the protein. In family II, 1 girl and 1 boy were homozygous for a transversion changing conserved histidine 254 into a glutamine. Both homozygous girls were normal. In the homozygous males, the degree of development of Müllerian derivatives was variable. The uterus was well developed in 2 boys of family I and in the patient from family II; however, in 1 subject from family I, Müllerian derivatives were undetectable. Taken together, the diversity of clinical symptoms within the same sibship and the lack of correlation between the development of the Müllerian derivatives and the severity of the molecular defects suggest highly variable penetrance of the abnormal alleles and/or the existence of other genetic or epigenetic modifiers of gene expression. PMID:22584735

  3. Genetic homogeneity in Sjoegren-Larsson syndrome: Linkage to chromosome 17p in families of different non-Swedish ethnic origins

    SciTech Connect

    Rogers, G.R.; Lee, M.; Compton, J.G.

    1995-11-01

    Sjoegren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. Three United States families, three Egyptian families, and one Israeli Arab family were investigated for linkage of the SLS gene to a region of chromosome 17. Pairwise and multipoint linkage analysis with nine markers mapped the SLS gene to the same region of the genome as that reported in Swedish SLS pedigrees. Examination of recombinants by haplotype analysis showed that the gene lies in the region containing the markers D17S953, D17S805, D17S689, and D17S842. D17S805 is pericentromeric on 17p. Patients in two consanguineous Egyptian families were homozygous at the nine marker loci tested, and another patient from a third family was homozygous for eight of the nine, suggesting that within each of these families the region of chromosome 17 carrying the SLS gene is identical by descent. Linkage of the SLS gene to chromosome 17p in families of Arabic, mixed European, Native American, and Swedish descent provides evidence for a single SLS locus and should prove useful for diagnosis and carrier detection in worldwide cases. 25 refs., 4 figs., 1 tab.

  4. Small satellites

    NASA Technical Reports Server (NTRS)

    Thomas, P.; Veverka, J.; Dermott, S.

    1986-01-01

    Satellites smaller than Mimas (r = 195 km) are distinguished by irregular overall shapes and by rough limb topography. Material properties and impact cratering dominate the shaping of these objects. Long fragmentation histories can produce a variety of internal structures, but so far there is no direct evidence that any small satellite is an equilibrium ellipsoid made up of noncohesive gravitationally bound rubble. One many bodies that orbit close to their primary the tidal and rotational components of surface gravity strongly affect the directions of local g and thereby affect the redistribution of regolith by mass wasting. Downslope movement of regolith is extensive on Deimos, and is probably effective on many other small satellites. It is shown that in some cases observed patterns of downslope mass wasting cold produce useful constraints on the satellite's mean density. The diversity of features seen in the few high-resolution images of small satellites currently available suggests that these objects have undergone complex histories of cratering, fragmentation, and regolith evolution.

  5. Family Capital: Implications for Interventions with Families

    ERIC Educational Resources Information Center

    Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

    2011-01-01

    Social capital has been extensively discussed in the literature as building blocks that individuals and communities utilize to leverage system resources. Similarly, some families also create capital, which can enable members of the family, such as children, to successfully negotiate the outside world. Families in poverty confront serious…

  6. Improving Family Communications

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Listen Español Text Size Email Print Share Improving Family Communications Page Content Article Body How can I ...

  7. Normal Functioning Family

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  8. Family Reunion Health Guide

    MedlinePlus

    ... Phone (Continued) 1. Send a Kidney Health Message Hi Family, I came across this information and thought ... mails to family members. Before the Reunion 1. Hi family! Taking care of your kidneys is important. ...

  9. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  10. Developing Strengths in Families

    ERIC Educational Resources Information Center

    Bowman, Ted

    1976-01-01

    There are few descriptions of growth experiences for total families. This paper describes one such model. It expresses the conviction that families need opportunities to come together with other families to identify strengths, sharpen communication skills, and establish goals. (Author)

  11. 26 CFR 1.1366-3 - Treatment of family groups.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) INCOME TAXES Small Business Corporations and Their Shareholders § 1.1366-3 Treatment of family groups. (a) In general. Under section 1366(e), if an individual, who is a member of the family of one or... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Treatment of family groups. 1.1366-3 Section...

  12. Population policy and family planning.

    PubMed

    1977-01-01

    The secret of success of India's population policy is the multipronged approach. Conflicts between public beliefs, customs, and public interests in regard to family size must be resolved through effective educational measures. The state should avoid legal compulsion and rely on volumtary choice by married couples influenced by logical judgment, information, and persuasion. Instead of using coercion, research in specific regions, sub-regions, and local areas should assess feasibility in light of knowledge, attitude, and practice of birth control, and rational goals should be set. Health conditions, particularly of mother and child, are an important approach to fertility and family size. As long as the morbidity of infants is high, the motivation for small family size will be low. Women's education generally should be improved. Later age at marriage also contributed to small family size. Present population policy should be expanded to include a broad-based socioeconomic approach with a social security program. Development through improved agricultural and marketing conditions will distribute the economic benefits for and improve the welfare of the most backward people. Voluntary organizations must be involved in population programs because a wholly state-sponsored program will meet with apathy and disinterest.

  13. Families and family therapy in Hong Kong.

    PubMed

    Tse, Samson; Ng, Roger M K; Tonsing, Kareen N; Ran, Maosheng

    2012-04-01

    Family therapy views humans not as separate entities, but as embedded in a network of relationships, highlighting the reciprocal influences of one's behaviours on one another. This article gives an overview of family demographics and the implementation of family therapy in Hong Kong. We start with a review of the family demographics in Hong Kong and brief notes on families in mainland China. Demographics show that the landscape has changed markedly in the past decade, with more cross-border marriages, an increased divorce rate, and an ageing overall population - all of which could mean that there is increasing demand for professional family therapy interventions. However, only a limited number of professionals are practising the systems-based approach in Hong Kong. Some possible reasons as to why family therapy is not well disseminated and practised are discussed. These reasons include a lack of mental health policy to support family therapy, a lack of systematic family therapy training, and a shortage of skilled professionals. Furthermore, challenges in applying the western model in Chinese culture are also outlined. We conclude that more future research is warranted to investigate how family therapy can be adapted for Chinese families.

  14. Families and family therapy in Hong Kong.

    PubMed

    Tse, Samson; Ng, Roger M K; Tonsing, Kareen N; Ran, Maosheng

    2012-04-01

    Family therapy views humans not as separate entities, but as embedded in a network of relationships, highlighting the reciprocal influences of one's behaviours on one another. This article gives an overview of family demographics and the implementation of family therapy in Hong Kong. We start with a review of the family demographics in Hong Kong and brief notes on families in mainland China. Demographics show that the landscape has changed markedly in the past decade, with more cross-border marriages, an increased divorce rate, and an ageing overall population - all of which could mean that there is increasing demand for professional family therapy interventions. However, only a limited number of professionals are practising the systems-based approach in Hong Kong. Some possible reasons as to why family therapy is not well disseminated and practised are discussed. These reasons include a lack of mental health policy to support family therapy, a lack of systematic family therapy training, and a shortage of skilled professionals. Furthermore, challenges in applying the western model in Chinese culture are also outlined. We conclude that more future research is warranted to investigate how family therapy can be adapted for Chinese families. PMID:22515459

  15. Homozygous 16p13.11 duplication associated with mild intellectual disability and urinary tract malformations in two siblings born from consanguineous parents.

    PubMed

    Houcinat, N; Llanas, B; Moutton, S; Toutain, J; Cailley, D; Arveiler, B; Combe, C; Lacombe, D; Rooryck, C

    2015-11-01

    The use of array-comparative genomic hybridization (array-CGH) in routine clinical work has allowed the identification of many new copy number variations (CNV). The 16p13.11 duplication has been implicated in various congenital anomalies and neurodevelopmental disorders, but it has also been identified in healthy individuals. We report a clinical observation of two brothers from related parents each carrying a homozygous 16p13.11 duplication. The propositus had mild intellectual disability and posterior urethral valves with chronic renal disease. His brother was considered a healthy child with only learning disabilities and poor academic performances. However, a routine medical examination at 25-years-old revealed a mild chronic renal disease and ureteropelvic junction obstruction. Furthermore, the father presented with a unilateral renal agenesis, thus it seemed that a "congenital anomalies of kidney and urinary tract" (CAKUT) phenotype segregated in this family. This may be related to the duplication, but we cannot exclude the involvement of additional genetic or non-genetic factors in the urological phenotype. Several cohort studies showed association between this chromosomal imbalance and different clinical manifestations, but rarely with CAKUT. The duplication reported here was similar to the larger one of 3.4 Mb previously described versus the more common of 1.6 Mb. It encompassed at least 11 known genes, including the five ohnologs previously identified. Our observation, in addition to expanding the clinical spectrum of the duplication provides further support to understanding the underlying pathogenic mechanism.

  16. The Clinical Features and Diagnosis of Adrenoleukodystrophy: A Case Series of Iranian Family

    PubMed Central

    KARIMZADEH, Parvaneh; JAFARI, Narjes; NEJAD BIGLARI, Habibe; JABBEHDARI, Sayena; ALIZADEH, Mehdi; ALIZADEH, Ghazal; NEJAD BIGLARI, Hamid; SANII, Sara

    2016-01-01

    Objective Adrenoleukodystrophy disorder is one of the x-linked genetic disorders caused by the myelin sheath breakdown in the brain. In this study, we present 4 yr experience on this disorder. Materials & Methods The patients diagnosed as adrenoleukodystrophy in the Neurology Department of Mofid Children’s Hospital in Tehran, Iran from 2010 to 2014 were enrolled into the study. The disorder was confirmed by neuroimaging and clinical findings along with genetic and neurometabolic assessment at Reference Laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of populous family with adrenoleukodystrophy. Results All of the patients were one populous family with high rate of consanguineous marriages. This disorder was confirmed by genetic assessment, VLCFA and brain MRI. c.253_254insC, p.R85Pfs112* was found in heterozygote state and the VLCFA assessment showed the typical pattern for adrenoleukodystrophy/ adrenomyeloneuropathy. This diagnosis was in agreement with the family history and the clinical history of the patient. Since there have been a number of cases in patient’s family in the past, so intensive follow-up on the family especially detection the female members of the family of childbearing age was recommended. The amount of C-26, C24/C22 and C26/C22 was elevated. All patients with the same genotype had wide ranges of clinical presentation. Conclusion Early diagnose of this disease might help us for early intervention and prenatal diagnosis for the disease in next siblings. PMID:27057190

  17. 'I don't see any point in telling them': attitudes to sharing genetic information in the family and carrier testing of relatives among British Pakistani adults referred to a genetics clinic.

    PubMed

    Shaw, Alison; Hurst, Jane A

    2009-04-01

    The sharing of genetic information following the diagnosis of a genetic condition can be important for managing familial risks for genetic conditions. This paper explores factors that impede or facilitate the sharing of genetic information within a sample of British Pakistani families. It draws from research investigating understandings of genetics and inheritance, attitudes to prenatal diagnosis and risk communication in the family that used methods of participant observation and interview with adults from 66 families of Pakistani origin referred to a genetics clinic in southern England. We found a lack of English often restricted one partner's access to genetic information and partners fluent in English sometimes withheld information to protect a partner (usually the wife) from blame, stigma or feelings of marital insecurity. Many couples felt genetic information was private to them as a couple and were unwilling to share it with the wider family, commenting on its potentially stigmatizing and emotionally and socially disruptive effects on themselves, their child and their marriage, as well as on the marriage prospects of other family members. Those who sought carrier testing because of a family history did so when considering their own marriage or parenting, sometimes on the insistence of an affected relative, but did not readily discuss carrier testing with other relatives. Despite the complex consanguinity in some families, a family-based approach to risk management is not necessarily any easier among British Pakistanis than other ethnic groups. PMID:19052940

  18. Discovery of a Promiscuous Non-Heme Iron Halogenase in Ambiguine Alkaloid Biogenesis: Implication for an Evolvable Enzyme Family for Late-Stage Halogenation of Aliphatic Carbons in Small Molecules.

    PubMed

    Hillwig, Matthew L; Zhu, Qin; Ittiamornkul, Kuljira; Liu, Xinyu

    2016-05-01

    The elucidation of enigmatic enzymatic chlorination timing in ambiguine indole alkaloid biogenesis led to the discovery and characterization of AmbO5 protein as a promiscuous non-heme iron aliphatic halogenase. AmbO5 was shown capable of selectively modifying seven structurally distinct ambiguine, fischerindole and hapalindole alkaloids with chlorine via late-stage aliphatic C-H group functionalization. Cross-comparison of AmbO5 with a previously characterized aliphatic halogenase homolog WelO5 that has a restricted substrate scope led to the identification of a C-terminal sequence motif important for substrate tolerance and specificity. Mutagenesis of 18 residues of WelO5 within the identified sequence motif led to a functional mutant with an expanded substrate scope identical to AmbO5, but an altered substrate specificity from the wild-type enzymes. These observations collectively provide evidence on the evolvable nature of AmbO5/WelO5 enzyme duo in the context of hapalindole-type alkaloid biogenesis and implicate their promise for the future development of designer biocatalysis for the selective late-stage modification of unactivated aliphatic carbon centers in small molecules with halogens. PMID:27027281

  19. Seven New Complete Plastome Sequences Reveal Rampant Independent Loss of the ndh Gene Family across Orchids and Associated Instability of the Inverted Repeat/Small Single-Copy Region Boundaries

    PubMed Central

    Moore, Michael J.; Neubig, Kurt M.; Williams, Norris H.; Whitten, W. Mark; Kim, Joo-Hwan

    2015-01-01

    Earlier research has revealed that the ndh loci have been pseudogenized, truncated, or deleted from most orchid plastomes sequenced to date, including in all available plastomes of the two most species-rich subfamilies, Orchidoideae and Epidendroideae. This study sought to resolve deeper-level phylogenetic relationships among major orchid groups and to refine the history of gene loss in the ndh loci across orchids. The complete plastomes of seven orchids, Oncidium sphacelatum (Epidendroideae), Masdevallia coccinea (Epidendroideae), Sobralia callosa (Epidendroideae), Sobralia aff. bouchei (Epidendroideae), Elleanthus sodiroi (Epidendroideae), Paphiopedilum armeniacum (Cypripedioideae), and Phragmipedium longifolium (Cypripedioideae) were sequenced and analyzed in conjunction with all other available orchid and monocot plastomes. Most ndh loci were found to be pseudogenized or lost in Oncidium, Paphiopedilum and Phragmipedium, but surprisingly, all ndh loci were found to retain full, intact reading frames in Sobralia, Elleanthus and Masdevallia. Character mapping suggests that the ndh genes were present in the common ancestor of orchids but have experienced independent, significant losses at least eight times across four subfamilies. In addition, ndhF gene loss was correlated with shifts in the position of the junction of the inverted repeat (IR) and small single-copy (SSC) regions. The Orchidaceae have unprecedented levels of homoplasy in ndh gene presence/absence, which may be correlated in part with the unusual life history of orchids. These results also suggest that ndhF plays a role in IR/SSC junction stability. PMID:26558895

  20. Family self-tailoring: Applying a systems approach to improving family healthy living behaviors.

    PubMed

    Moore, Shirley M; Jones, Lenette; Alemi, Farrokh

    2016-01-01

    The adoption and maintenance of healthy living behaviors by individuals and families is a major challenge. We describe a new model of health behavior change, SystemCHANGE (SC), which focuses on the redesign of family daily routines using system improvement methods. In the SC intervention, families are taught a set of skills to engage in a series of small, family self-designed experiments to test ideas to change their daily routines. The family system-oriented changes brought about by these experiments build healthy living behaviors into family daily routines so that these new behaviors happen as a matter of course, despite wavering motivation, willpower, or personal effort on the part of individuals. Case stories of the use of SC to improve family healthy living behaviors are provided. Results of several pilot tests of SC indicate its potential effectiveness to change health living behaviors across numerous populations.

  1. Family science: What is it?

    SciTech Connect

    Whitlow, B.

    1994-12-31

    Family science is an informal science education program designed to teach science skills by having children and parents learn and enjoy science together. Aimed at addressing the underrepresentation of women and ethnic and racial minorities in science-based careers, FAMILY SCIENCE involves parents and children in kindergarten through eighth grade in science activities that demonstrate the role science plays in their daily life and future. Family involvement is the key to the program`s effectiveness. Family classes are usually offered in a series of one- to two-hour class meetings for parents and their children after school, evenings, and weekends. During classes, parents and children work in pairs and small groups to solve problems, work cooperatively, and talk science. The activities provide experiences for the entire family that build skills, confidence, and interest in science. In addition, guest speakers and career activities illustrate for parents in the workforce the significance of math and science in their own jobs, and for kids, it highlights the diversity of jobs and the relevance of math and science.

  2. Medicaid and Family Wealth Transfer

    PubMed Central

    Lee, Jinkook; Kim, Hyungsoo; Tanenbaum, Sandra

    2006-01-01

    Purpose: This study examines whether the relationship between making familial wealth transfers and becoming a Medicaid recipient sheds light on the current debate about Medicaid estate planning, whereby some elders transfer their assets to their families to qualify for Medicaid. Design and Methods: Using the Health and Retirement Study, we tracked a national sample of community-based elders who did not receive Medicaid at the 1993 baseline interview but became Medicaid recipients during a 10-year time period and examined wealth transfers for these new Medicaid beneficiaries. Results: Among elders aged 70 or older who did not receive Medicaid in 1993, 16.4% became Medicaid recipients over 10 years. Among these new Medicaid recipients, 17.9% transferred their wealth to family members before receiving Medicaid benefits, with an average transfer amount of $8,507 during the 2 years prior to receiving Medicaid benefits. In addition, 15.2% of community-residing elders entered a nursing home during the 10-year period, and 26.3% of these were covered by Medicaid. Of these new Medicaid recipients living in nursing homes, 12.6% transferred wealth to their families in the mean amount of $4,112. Implications: Familial wealth transfers do occur before changes in Medicaid eligibility in a small, but nontrivial, number of cases, but the amount transferred is modest, especially among nursing home residents. This finding implies that policies to reduce Medicaid long-term-care expenditures by limiting such transfers may not be very effective. PMID:16452279

  3. Homozygous 16p13.11 duplication associated with mild intellectual disability and urinary tract malformations in two siblings born from consanguineous parents.

    PubMed

    Houcinat, N; Llanas, B; Moutton, S; Toutain, J; Cailley, D; Arveiler, B; Combe, C; Lacombe, D; Rooryck, C

    2015-11-01

    The use of array-comparative genomic hybridization (array-CGH) in routine clinical work has allowed the identification of many new copy number variations (CNV). The 16p13.11 duplication has been implicated in various congenital anomalies and neurodevelopmental disorders, but it has also been identified in healthy individuals. We report a clinical observation of two brothers from related parents each carrying a homozygous 16p13.11 duplication. The propositus had mild intellectual disability and posterior urethral valves with chronic renal disease. His brother was considered a healthy child with only learning disabilities and poor academic performances. However, a routine medical examination at 25-years-old revealed a mild chronic renal disease and ureteropelvic junction obstruction. Furthermore, the father presented with a unilateral renal agenesis, thus it seemed that a "congenital anomalies of kidney and urinary tract" (CAKUT) phenotype segregated in this family. This may be related to the duplication, but we cannot exclude the involvement of additional genetic or non-genetic factors in the urological phenotype. Several cohort studies showed association between this chromosomal imbalance and different clinical manifestations, but rarely with CAKUT. The duplication reported here was similar to the larger one of 3.4 Mb previously described versus the more common of 1.6 Mb. It encompassed at least 11 known genes, including the five ohnologs previously identified. Our observation, in addition to expanding the clinical spectrum of the duplication provides further support to understanding the underlying pathogenic mechanism. PMID:26114937

  4. IDENTIFYING COLLISIONAL FAMILIES IN THE KUIPER BELT

    SciTech Connect

    Marcus, Robert A.; Ragozzine, Darin; Murray-Clay, Ruth A.; Holman, Matthew J.

    2011-05-20

    The identification and characterization of numerous collisional families-clusters of bodies with a common collisional origin-in the asteroid belt has added greatly to the understanding of asteroid belt formation and evolution. More recent study has also led to an appreciation of physical processes that had previously been neglected (e.g., the Yarkovsky effect). Collisions have certainly played an important role in the evolution of the Kuiper Belt as well, though only one collisional family has been identified in that region to date, around the dwarf planet Haumea. In this paper, we combine insights into collisional families from numerical simulations with the current observational constraints on the dynamical structure of the Kuiper Belt to investigate the ideal sizes and locations for identifying collisional families. We find that larger progenitors (r {approx} 500 km) result in more easily identifiable families, given the difficulty in identifying fragments of smaller progenitors in magnitude-limited surveys, despite their larger spread and less frequent occurrence. However, even these families do not stand out well from the background. Identifying families as statistical overdensities is much easier than characterizing families by distinguishing individual members from interlopers. Such identification seems promising, provided the background population is well known. In either case, families will also be much easier to study where the background population is small, i.e., at high inclinations. Overall, our results indicate that entirely different techniques for identifying families will be needed for the Kuiper Belt, and we provide some suggestions.

  5. Making Time for Family.

    ERIC Educational Resources Information Center

    Newman, Rita

    1998-01-01

    Reviews Covey's "7 Habits of Effective Families," noting that time plays an important part in each habit. Discusses several important "time" issues for families: time to plan for time, time for awareness of quality time, time to have two-way communication, time for family moments, and time to reflect. Includes suggestions for family activities in…

  6. Families in Transition .

    ERIC Educational Resources Information Center

    Bundy, Michael L., Ed.; Gumaer, James, Ed.

    1984-01-01

    Focuses on disrupted families and the role of the school counselor in helping children adjust. Describes characteristics of healthy families, and discusses the transition to the blended family, effects of divorce groups on children's classroom behavior, counseling children in stepfamilies, single-parent families, and parenting strengths of single…

  7. Black Families. Third Edition.

    ERIC Educational Resources Information Center

    McAdoo, Harriette Pipes, Ed.

    The chapters of this collection explore the experiences of black families in the United States and Africa, today and in the past. They are: (1) "African American Families: A Historical Note" (John Hope Franklin); (2) "African American Families and Family Values" (Niara Sudarkasa); (3) "Old-Time Religion: Benches Can't Say 'Amen'" (William Harrison…

  8. Gavin Families. A Report.

    ERIC Educational Resources Information Center

    Weaver, Paul Neufeld; And Others

    The Family Literacy Project at the Dr. Charles E. Gavin School in Chicago Heights, Illinois, brings together a community college adult education program, an early childhood program, and a local school district. This report of the Prairie State College Family Literacy Project assesses the needs for family literacy among the families in the Gavin…

  9. Familial Ebstein's anomaly.

    PubMed Central

    Rosenmann, A; Arad, I; Simcha, A; Schaap, T

    1976-01-01

    A family is described in which both a father and son are affected with Ebstein's anomaly, while several other family members manifest different cardiac malformations. Five additional instances of familial Ebstein's anomaly were found in the literature and compared with our family. Inspection of possible modes of inheritance in this group of families suggests that Ebstein's anomaly is probably inherited as a polygenic character with a threshold phenomenon. PMID:1018315

  10. Small GTPases in vesicle trafficking.

    PubMed

    Molendijk, Arthur J; Ruperti, Benedetto; Palme, Klaus

    2004-12-01

    Plant small GTPases belonging to the Rop, Arf, and Rab families are regulators of vesicle trafficking. Rop GTPases regulate actin dynamics and modulate H(2)O(2) production in polar cell growth and pathogen defence. A candidate Rop GDP to Rop GTP exchange factor (RopGEF) SPIKE1 is involved in the morphogenesis of leaf epidermal cells. The ArfGEF GNOM regulates the endosomal recycling of the PIN proteins, which are involved in polar auxin transport. Intracellular localisation of small GTPases and functional studies using dominant mutant versions of Arf and Rab GTPases are defining novel plant-specific membrane compartments, especially those that participate in endosomal vesicle trafficking.

  11. Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy.

    PubMed

    Thomas, P M; Cote, G J; Hallman, D M; Mathew, P M

    1995-02-01

    Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a rare, autosomal recessive disease of unregulated insulin secretion, defined by elevations in serum insulin despite severe hypoglycemia. We used the homozygosity gene-mapping strategy to localize this disorder to the region of chromosome 11p between markers D11S1334 and D11S899 (maximum LOD score 5.02 [theta = 0] at marker D11S926) in five consanguineous families of Saudi Arabian origin. These results extend those of a recent report that also placed PHHI on chromosome 11p, between markers D11S926 and D11S928. Comparison of the boundaries of these two overlapping regions allows the PHHI locus to be assigned to the 4-cM region between the markers D11S926 and D11S899. Identification of this gene may allow a better understanding of other disorders of glucose homeostasis, by providing insight into the regulation of insulin release.

  12. Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy

    SciTech Connect

    Thomas, P.M.; Cote, G.J.; Hallman, D.M.; Mathew, P.M.

    1995-02-01

    Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a rare, autosomal recessive disease of unregulated insulin secretion, defined by elevations in serum insulin despite severe hypoglycemia. We used the homozygosity gene-mapping strategy to localize this disorder to the region of chromosome 11p between markers D11S1334 and D11S899 (maximum LOD score 5.02 [{theta} = 0] at marker D11S926) in five consanguineous families of Saudi Arabian origin. These results extend those of a recent report that also placed PHHI on chromosome 11p, between markers D11S926 and D11S928. Comparison of the boundaries of these two overlapping regions allows the PHHI locus to be assigned to the 4-cM region between the markers D11S926 and D11S899. Identification of this gene may allow a better understanding of other disorders of glucose homeostasis, by providing insight into the regulation of insulin release. 37 refs., 2 figs., 4 tabs.

  13. [Mutation analysis of the pathogenic gene in a Chinese family with hereditary hemochromatosis].

    PubMed

    Yuanfeng, Li; Hongxing, Zhang; Haitao, Zhang; Xiaobo, Peng; Lili, Bai; Fuchu, He; Zewu, Qiu; Gangqiao, Zhou

    2014-11-01

    Hereditary hemochromatosis (HHC) is a rare autosomal recessive disorder. We recruited a consanguineous Chinese family including the proband with HHC and other four members without HHC. Using whole-exome sequencing, we identified two homozygous mutations (c.G18C [p.Q6H] and c.GC962_963AA [p.C321X]) in the hemojuvelin gene (HJV) in the proband with HHC. No mutation was found in other four previously identified HHC related genes, HAMP, TFR2, FPN and HFE. The functional impact of p.Q6H mutation is weak whereas p.C321X, a premature termination mutation, results in a truncated HJV protein, which lacks the glycosylphosphatidylinositol (GPI) anchor domain. In addition to the mutations in HJV, other 12 homozygous mutations were identified in this patient. However, none of these mutations showed strong damaging impact and the mutated genes are not related to iron metabolism. Our in-house data further demonstrated that p.C321X is absent in the general Chinese population, suggesting that the homozygous mutation p.C321X in HJV is causative in the patient with HHC. Accordingly, all of the four members without HHC from the same family carried wild-type alleles or heterozygous mutations, but not the homozygous mutation in this site. Thus, we found for the first time that the homozygous mutation p.C321X in HJV can result in HHC, which will help genetic diagnosis and prenatal counseling for HHC.

  14. Isolated familial somatotropinomas: clinical features and analysis of the MEN1 gene.

    PubMed

    De Menis, Ernesto; Prezant, Toni R

    2002-01-01

    Isolated familial somatotropinomas (IFS) rarely occurs in the absence of multiple endocrine neoplasia type I (MEN1) or the Carney complex. In the present study we report two Italian siblings affected by GH-secreting adenomas. There was no history of parental consanguinity. The sister presented at 18 years of age with secondary amenorrhea and acromegalic features and one of her two brothers presented with gigantism at the same age. Endocrinological investigations confirmed GH hypersecretion in both cases. Although a pituitary microadenoma was detected in both patients, transsphenoidal surgery was not successful. The sister received conventional radiotherapy and acromegaly is now considered controlled; the brother is being treated with octreotide LAR 30 mg monthly and the disease is considered clinically active. Patients, their parents and the unaffected brother underwent extensive evaluation, and no features of MEN1 or Carney complex were found. Analysis of polymorphic microsatellite markers from chromosome 11q13 (D11S599, D11S4945, D11S4939, D11S4938 and D11S987) showed that the acromegalic siblings had inherited different maternal chromosomes and shared the paternal chromosome. No pathogenic MEN1 sequence changes were detected by sequencing or dideoxy fingerprinting of the coding sequence (exons 2-10) and exon/intron junctions. Although mutations in the promoter, introns or untranslated regions of the MEN1 gene cannot be excluded, germline mutations within the coding region of this gene do not appear responsible for IFS in this family. PMID:12638720

  15. Nontraditional family romance.

    PubMed

    Corbett, K

    2001-07-01

    Family stories lie at the heart of psychoanalytic developmental theory and psychoanalytic clinical technique, but whose family? Increasingly, lesbian and gay families, multiparent families, and single-parent families are relying on modern reproductive technologies to form families. The contemplation of these nontraditional families and the vicissitudes of contemporary reproduction lead to an unknowing of what families are, including the ways in which psychoanalysts configure the family within developmental theory. This article focuses on the stories that families tell in order to account for their formation--stories that include narratives about parental union, parental sexuality, and conception. The author addresses three constructs that inform family stories and that require rethinking in light of the category crises posed by and for the nontraditional family: (1) normative logic, (2) family reverie and the construction of a family romance, and (3) the primal scene. These constructs are examined in tandem with detailed clinical material taken from the psychotherapy of a seven-year-old boy and his two mothers.

  16. Nontraditional family romance.

    PubMed

    Corbett, K

    2001-07-01

    Family stories lie at the heart of psychoanalytic developmental theory and psychoanalytic clinical technique, but whose family? Increasingly, lesbian and gay families, multiparent families, and single-parent families are relying on modern reproductive technologies to form families. The contemplation of these nontraditional families and the vicissitudes of contemporary reproduction lead to an unknowing of what families are, including the ways in which psychoanalysts configure the family within developmental theory. This article focuses on the stories that families tell in order to account for their formation--stories that include narratives about parental union, parental sexuality, and conception. The author addresses three constructs that inform family stories and that require rethinking in light of the category crises posed by and for the nontraditional family: (1) normative logic, (2) family reverie and the construction of a family romance, and (3) the primal scene. These constructs are examined in tandem with detailed clinical material taken from the psychotherapy of a seven-year-old boy and his two mothers. PMID:11491437

  17. 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.

  18. Family Synergy, A Variant Family Organization

    ERIC Educational Resources Information Center

    LaFollette, Patrick

    1975-01-01

    This article describes "Family Synergy" which is a non-profit organization for people interested in or exploring nontraditional marriage and family forms. It acts as a clearinghouse for the exchange of ideas and also provides a supportive community for people actually exploring these new lifestyles. (Author)

  19. Families and Family Study in International Perspective

    ERIC Educational Resources Information Center

    Adams, Bert N.

    2004-01-01

    Many changes are occurring in the world's families. Some observers feel that the changes are destructive, whereas others see them as leading to new opportunities and understanding. Issues in international family studies include regional limitations and the various aspects of doing research cross-culturally. Knowledge regarding certain categories…

  20. Mental health issues of Maria I of Portugal and her sisters: the contributions of the Willis family to the development of psychiatry.

    PubMed

    Peters, Timothy J; Willis, Clive

    2013-09-01

    Contemporary accounts credit Dr Francis Willis (1718-1807) with facilitating the recovery of King George III from his major episode of acute mania in 1788-9. Subsequently Willis was summoned to Lisbon to advise on the mental health problems of Queen Maria I. This article reports the nature of the illnesses of Maria and her two similarly affected sisters, and uses the program OPCRIT to propose diagnoses of major depressive disorders. The high prevalence of consanguinity and insanity among the Portuguese monarchy and their antecedents probably contributed to their mental health problems. The successive contributions of the Willis family from Thomas Willis (1621-75) to his grand-nephew, Francis Willis (1792-1859), are reviewed; the popular image is somewhat inaccurate and does not highlight their part in the development of psychiatry.

  1. Mental health issues of Maria I of Portugal and her sisters: the contributions of the Willis family to the development of psychiatry.

    PubMed

    Peters, Timothy J; Willis, Clive

    2013-09-01

    Contemporary accounts credit Dr Francis Willis (1718-1807) with facilitating the recovery of King George III from his major episode of acute mania in 1788-9. Subsequently Willis was summoned to Lisbon to advise on the mental health problems of Queen Maria I. This article reports the nature of the illnesses of Maria and her two similarly affected sisters, and uses the program OPCRIT to propose diagnoses of major depressive disorders. The high prevalence of consanguinity and insanity among the Portuguese monarchy and their antecedents probably contributed to their mental health problems. The successive contributions of the Willis family from Thomas Willis (1621-75) to his grand-nephew, Francis Willis (1792-1859), are reviewed; the popular image is somewhat inaccurate and does not highlight their part in the development of psychiatry. PMID:24573446

  2. Invest in Family*

    PubMed Central

    Shah, Nilesh; De Sousa, Avinash

    2015-01-01

    The family is an integral part of one's life. It is very essential that every individual employed or unemployed invests time therein. The family is a source of support and growth for an individual, and the lack of family support or loneliness may be a causative factor in the genesis of psychiatric disorders, especially depression. In India, family plays a paramount role when it comes to mental health of the individual. Tips on how one should invest time in one's family along with the role of a family in one's personal and social structure are discussed. PMID:25838732

  3. 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.

  4. Familial Pulmonary Fibrosis

    MedlinePlus

    ... are here: Health Information > Condition Information Familial Pulmonary Fibrosis: Overview When two or more members within the ... Associate Professor View full profile More Familial Pulmonary Fibrosis Information Forms Causes Genetic Counseling Print Page Email ...

  5. Evaluation of family therapy.

    PubMed

    Nielsen, Nanna

    2006-01-01

    Because children of mentally disordered parents have an increased risk of becoming subjects of mental disorder and psychological problems, adult psychiatry has increasingly paid attention to the patients' parental skills. This study includes 31 families with children younger than 18 years of age where the parents were admitted to family therapy in an open psychiatric ward. The average number of sessions was seven, and the diagnoses of severe stress and of adjustment disorder were the most common. The aim of the study was to measure changes in the family climate during the period of therapy. The instrument used was the Family Environment Scale (FES), a self-rating questionnaire that measures the parents' experience of family environment. The change of family environment is related to its influence on children's well-being and development. The study finds that family therapy has resulted in positive changes of the parents' experience of the family climate.

  6. Normative Family Development.

    ERIC Educational Resources Information Center

    Barcai, Avner

    1981-01-01

    Describes the sequentially developmental life stages of healthy, normal families. Provides an exposition of these developmental stages and forms as a guide or normative framework within which to test for dysfunction and pathology in the family process. (Author/JAC)

  7. MSUD Family Support Group

    MedlinePlus

    ... Group The MSUD Family Support Group is a non-profit 501 (c)(3) organization for those with MSUD ... Family Support Group is a 501(c)(3) non-profit organization with no paid staff. Funds are needed ...

  8. Assessing postpartum family functioning.

    PubMed

    Midmer, D; Talbot, Y

    1988-09-01

    The birth of a child requires adaptation and reorganization within the family system in order to accommodate the new family member and to allow the family to continue in its psychosocial development. Knowledge of the normative and transitional changes required at this stage of family life will enhance family practitioners' understanding of some of the common concerns and complaints related to them by various family members during the postpartum period. The Family FIRO model represents a helpful conceptual framework to increase the family physician's understanding of the issues of inclusion, control, and intimacy that are highlighted during the transition to parenthood. The authors briefly present this model and discuss its application to postpartum adjustment and its implications for health-care professionals.

  9. Assessing Postpartum Family Functioning

    PubMed Central

    Midmer, Deana; Talbot, Yves

    1988-01-01

    The birth of a child requires adaptation and reorganization within the family system in order to accommodate the new family member and to allow the family to continue in its psychosocial development. Knowledge of the normative and transitional changes required at this stage of family life will enhance family practitioners' understanding of some of the common concerns and complaints related to them by various family members during the postpartum period. The Family FIRO model represents a helpful conceptual framework to increase the family physician's understanding of the issues of inclusion, control, and intimacy that are highlighted during the transition to parenthood. The authors briefly present this model and discuss its application to postpartum adjustment and its implications for health-care professionals. PMID:21253238

  10. Familial Periodic Paralyses

    MedlinePlus

    ... NINDS NINDS Familial Periodic Paralyses Information Page Synonym(s): Periodic Paralyses Table of Contents (click to jump to sections) What are Familial Periodic Paralyses? Is there any treatment? What is the ...

  11. Importance of Family Routines

    MedlinePlus

    ... Listen Español Text Size Email Print Share The Importance of Family Routines Page Content ​Every family needs ... child to sleep. These rituals can include storytelling, reading aloud, conversation, and songs. Try to avoid exciting ...

  12. The plant ADH gene family.

    PubMed

    Strommer, Judith

    2011-04-01

    The structures, evolution and functions of alcohol dehydrogenase gene families and their products have been scrutinized for half a century. Our understanding of the enzyme structure and catalytic activity of plant alcohol dehydrogenase (ADH-P) is based on the vast amount of information available for its animal counterpart. The probable origins of the enzyme from a simple β-coil and eventual emergence from a glutathione-dependent formaldehyde dehydrogenase have been well described. There is compelling evidence that the small ADH gene families found in plants today are the survivors of multiple rounds of gene expansion and contraction. To the probable original function of their products in the terminal reaction of anaerobic fermentation have been added roles in yeast-like aerobic fermentation and the production of characteristic scents that act to attract animals that serve as pollinators or agents of seed dispersal and to protect against herbivores.

  13. 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

  14. Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families.

    PubMed

    Hyun, Young Se; Lee, Jinho; Kim, Hye Jin; Hong, Young Bin; Koo, Heasoo; Smith, Alec S T; Kim, Deok-Ho; Choi, Byung-Ok; Chung, Ki Wha

    2015-11-01

    Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive demyelinating subtype of peripheral enuropathies caused by mutations in the FGD4 gene. Most CMT4H patients are in consanguineous Mediterranean families characterized by early onset and slow progression. We identified two CMT4H patients from a Korean CMT cohort, and performed a detailed genetic and clinical analysis in both cases. Both patients from nonconsanguineous families showed characteristic clinical manifestations of CMT4H including early onset, scoliosis, areflexia, and slow disease progression. Exome sequencing revealed novel compound heterozygous mutations in FGD4 as the underlying cause in both families (p.Arg468Gln and c.1512-2A>C in FC73, p.Met345Thr and c.2043+1G>A (p.Trp663Trpfs*30) in FC646). The missense mutations were located in highly conserved RhoGEF and PH domains which were predicted to be pathogenic in nature by in silico modeling. The CMT4H occurrence frequency was calculated to 0.7% in the Korean demyelinating CMT patients. This study is the first report of CMT4H in Korea. FGD4 assay could be considered as a means of molecular diagnosis for sporadic cases of demyelinating CMT with slow progression.

  15. Familial spastic paraplegia with distal muscle wasting in the Old Order Amish; atypical Troyer syndrome or "new" syndrome.

    PubMed

    Neuhäuser, G; Wiffler, C; Opitz, J M

    1976-03-01

    The Troyer syndrome was found by Cross & McKusick (1967) in 20 members of 12 Old Order Amish families in Holmes County, Ohio; it is a form of hereditary spastic paraplegia combined with distal muscle wasting, i.e. signs of involvement of lower motor neurons. The condition usually begins at 1 to 2 years and progresses at variable rates. Further manifestations include growth retardation, delayed speech development with dysarthria and drooling, and cerebellar signs; mental functions are usually not affected but severe emotional lability is a common finding. Brothers in a Wisconsin Old Order Amish family are reported with spastic diplegia, mental retardation, behavioral disorder and shortness of stature; the condition apparently is not progressive, and may be a "new" syndrome but could also represent a variant of the Troyer syndrome. Autosomal recessive inheritance is most likely, although consanguinity of the parents could not be proven. Another child in this family suffers from focal scleroderma (morphea) which is not related to the neurological syndrome. PMID:1261070

  16. A homozygous frameshift mutation in the HOXC13 gene underlies pure hair and nail ectodermal dysplasia in a Syrian family.

    PubMed

    Farooq, Muhammad; Kurban, Mazen; Fujimoto, Atsushi; Fujikawa, Hiroki; Abbas, Ossama; Nemer, Georges; Saliba, Jessica; Sleiman, Rima; Tofaili, Mona; Kibbi, Abdul-Ghani; Ito, Masaaki; Shimomura, Yutaka

    2013-04-01

    Pure hair and nail ectodermal dysplasia (PHNED) is a rare genetic disorder characterized by hypotrichosis or complete alopecia, as well as nail dystrophy. Mutations in the type II hair keratin gene KRT85 and the HOXC13 gene on chromosome 12q have recently been identified in families with autosomal-recessive PHNED. In the present study, we have analyzed a consanguineous Syrian family with an affected girl having complete alopecia and nail dystrophy since birth. The family clearly showed linkage to chromosome 12q13.13-12q14.3, which excluded the KRT85 gene. Sequencing of another candidate gene HOXC13 within the linkage interval identified a homozygous frameshift mutation (c.355delC; p.Leu119Trpfs*20). Expression studies in cultured cells revealed that the mutant HOXC13 protein mislocalized within the cytoplasm, and failed to upregulate the promoter activities of its target genes. Our results strongly suggest crucial roles of the HOXC13 gene in the development of hair and nails in humans.

  17. WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease.

    PubMed

    Covone, A E; Fiorillo, C; Acquaviva, M; Trucco, F; Morana, G; Ravazzolo, R; Minetti, C

    2016-08-01

    We have performed whole-exome sequencing in a family trio with a 16-year-old girl suffering of progressive motor neuron disease. There was no family history of the disease and no parental consanguinity. Our exome analysis indicated the proband as a compound heterozygote for two missense variants in the TECPR2 gene according to a recessive mode of inheritance. The TECPR2 gene has been reported as a positive regulator of autophagy which is an essential mechanism for maintaining neuron homeostasis and survival and plays a key role in major adult and pediatric neurodegenerative diseases. Variants in this gene have been found responsible for a recently described form of hereditary spastic paraplegia called SPG49 in two previous reports. We propose that both variants causing amino acid substitution, p.Leu684Val and p.Thr903Met, inherited in trans-phase compound heterozygote form, can be responsible for the phenotype observed in our patient. We also consider the possible contribution of a heterozygous variant in the SPG7 gene. Sanger sequencing confirmed the segregation of variants within the family tree including the patient's unaffected brother. PMID:27406698

  18. 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.

  19. Severe phenotypes in two Tunisian families with novel XPA mutations: evidence for a correlation between mutation location and disease severity.

    PubMed

    Messaoud, O; Rekaya, M Ben; Ouragini, H; Benfadhel, S; Azaiez, H; Kefi, R; Gouider-Khouja, N; Mokhtar, I; Amouri, A; Boubaker, M S; Zghal, M; Abdelhak, S

    2012-03-01

    Xeroderma pigmentosum (XP) is a rare disorder characterized by a high skin sun-sensitivity predisposing to skin cancers at an early age. Among Tunisian XP patients with an intermediate skin phenotype, 92% presented neurological abnormalities related to XPA gene deficiency. Clinical variability of the XP-A phenotype is associated with a mutational heterogeneity. In the present study, two Tunisian families with severe dermatological and neurological XP phenotypes were investigated in order to determine clinical characteristics and genetic basis. Two Tunisian families with four XP affected children were examined in the Dermatology Department. Clinical features showed severe presentation of the disease. Coding regions of the XPA gene were analysed by direct sequencing. Results showed the presence of a novel mutation, p.E111X, in three patients belonging to the same family and presenting a very severe phenotype i.e. development of skin lesions and neurological signs before 1 year age. For the other patient, we identified a nonsense mutation, p.R207X, already identified in a Palestinian XP-A patient. Identification of novel causing mutations in Tunisian XP-A patients shows the genetic and mutational heterogeneity of the disease in Tunisia. Despite a relatively homogenous mutational spectrum, mutational heterogeneity for rare cases is observed because of the high rate of consanguinity.

  20. Which family--what therapy: Maori culture, families and family therapy in New Zealand.

    PubMed

    Kumar, Shailesh; Dean, Peter; Smith, Barry; Mellsop, Graham W

    2012-04-01

    New Zealand is a relatively young and small country which has seen steady migration for nearly seven centuries. Despite a long history of rivalry and hostility between Maori and European values, the country has also seen some significant synergism between the two cultures. For the last three decades Asians have also migrated at a significant pace. The country faces the challenge of delivering quality mental health services to such cultures which are bifurcated in being socio-centric (Maori, Pacific Islanders and Asian total 32% combined) or ego-centric (European total 68%). Significant progress has been made in including families of the mentally ill in their treatment and care planning. Legislative requirements have been introduced for the family to be consulted in the treatment of those who are being compelled to receive psychiatric care under the Mental Health Act. Models of family therapy developed through innovation meeting the unique local needs or adaptation of existing models from overseas are being used. An overview of such family therapy modalities is presented.