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1

Familial accumulation of consanguineous marriages  

Microsoft Academic Search

Summary Distribution of consanguineous, marriages among spouses, husband's parents and wife's parents was analyzed based upon data on 20,563 families in six populations in Japan. There were highly significant correlations of presence or absence of consanguinity among the three couples in most populations. That is, products of consanguineous marriages tend to marry each other and a product of consanguineous marriage

Katumi Tanaka; Masako Tanimura

1977-01-01

2

Novel homozygous large deletion including the 5? part of the SPATA7 gene in a consanguineous Israeli Muslim Arab family  

PubMed Central

Purpose To identify the genetic defect in a consanguineous Israeli Muslim Arab family with juvenile retinitis pigmentosa (RP). Methods DNA samples were collected from the index patient, her parents, her affected sister, and two non-affected siblings. Genome-wide linkage analysis with 250 K single nucleotide polymorphism (SNP) arrays was performed using DNA from the two affected patients. Owing to consanguinity in the family, we applied homozygosity mapping to identify the disease-causing gene. The candidate gene SPATA7 was screened for mutations with PCR amplifications and direct Sanger sequencing. Results Following high-density SNP arrays, we identified several homozygous genomic regions one of which included the SPATA7 gene. Several mutations in SPATA7 have been reported for various forms of retinal dystrophy, including Leber congenital amaurosis (LCA) and juvenile RP. PCR-based sequence content mapping, long-distance PCR amplifications, and subsequent sequencing analysis revealed a homozygous 63.4 kb large deletion that encompasses the 5? part of the SPATA7 gene including exons 1–5. The mutation showed concordant segregation with the phenotype in the family as expected for autosomal recessive mode of inheritance and is consistent with a diagnosis of juvenile RP. Conclusions We report a novel homozygous large deletion in SPATA7 associated with juvenile RP in a consanguineous Israeli Muslim Arab family. This is the first larger deletion mutation reported for SPATA7. PMID:25814828

Mayer, Anja-Kathrin; Mahajnah, Muhammad; Zobor, Ditta; Bonin, Michael; Sharkia, Rajech

2015-01-01

3

Consanguinity and familial mental retardation.  

PubMed Central

Studies made in a group of patients with mental retardation showed that there was a high degree of parental consanguinity of the order of 30.3%. Index cases with parental consanguinity showed a relatively higher prevalence where more than one sib was affected. Cases with metabolic defects were also more common among cases with parental consanguinity. There is a need for studies in the general population in order to understand the biological significance of consanguinity. PMID:1271423

Sridhara Rama Rao, B S; Narayanan, H S

1976-01-01

4

Consanguinity and familial mental retardation  

Microsoft Academic Search

Studies made in a group of patients with mental retardation showed that there was a high degree of parental consanguinity of the order of 30.3%. Index cases with parental consanguinity showed a relatively higher prevalence where more than one sib was affected. Cases with metabolic defects were also more common among cases with parental consanguinity. There is a need for

B S Sridhara Rama Rao; H S Narayanan

1976-01-01

5

Linkage Analysis in a Large Family from Pakistan with Depression and a High Incidence of Consanguineous Marriages  

Microsoft Academic Search

Objectives: A genome wide scan for linkage was performed in a five generation family with a high incidence of depression and high average coefficient of inbreeding ascertained in a rural area of Pakistan. The effect of inbreeding on linkage analysis in an extended pedigree is discussed. Methods: 372 microsatellite markers were used in a genome wide linkage study. Inbreeding coefficients

Muhammad Ayub; Muhammad Irfan; Alan Maclean; Farooq Naeem; Stuart MacGregor; Peter M. Visscher; Walter Muir; Douglas Blackwood

2008-01-01

6

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

PubMed

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. PMID:24951542

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

7

Mutations in patients with osteogenesis imperfecta from consanguineous Indian families.  

PubMed

Osteogenesis imperfecta (OI) is a spectrum of genetic disorders with decreased bone density and bone fragility. Most of the cases of OI are inherited in autosomal dominant fashion with mutations in COL1A1 or COL1A2 genes. Over last few years, twelve genes for autosomal recessive OI have been identified. In this study we have evaluated seven patients with OI from consanguineous Indian families. Homozygosity mapping using SNP microarray was done and selected candidate genes were sequenced. Candidate genes were identified in four out of seven patients studied. Four mutations, namely; a homozygous non-sense (p.Q178*) and a deletion (p.F277del) mutations in SERPINF1 gene, a missense mutation (p.M101K) in PPIB gene and a nonsense mutation (p.E45*) in CRTAP gene were identified. In three patients for whom the regions of homozygosity did not reveal any known autosomal recessive OI genes, exome sequencing was performed and we identified a known missense mutation (p.G1012S) in COL1A2 gene in one of the patients. As WNT1 gene was not properly covered in exome sequencing in one patient, the gene was sequenced and a homozygous in-frame deletion of four amino acids (p.Phe176_Leu179del) was identified. In one of the three cases the exome sequencing did not reveal a mutation in any known OI genes, suggesting the possibility of mutations in an unidentified gene. The phenotypes of all the cases are described. This work proves the power of homozygosity mapping followed by candidate gene sequencing approach for clinical application in consanguineous families. PMID:25450603

Stephen, Joshi; Girisha, Katta Mohan; Dalal, Ashwin; Shukla, Anju; Shah, Hitesh; Srivastava, Priyanka; Kornak, Uwe; Phadke, Shubha R

2015-01-01

8

A novel HSF4 gene mutation (p.R405X) causing autosomal recessive congenital cataracts in a large consanguineous family from Pakistan  

Microsoft Academic Search

BACKGROUND: Hereditary cataracts are most frequently inherited as autosomal dominant traits, but can also be inherited in an autosomal recessive or X-linked fashion. To date, 12 loci for autosomal recessive cataracts have been mapped including a locus on chromosome 16q22 containing the disease-causing gene HSF4 (Genbank accession number NM_001040667). Here, we describe a family from Pakistan with the first nonsense

Naheed Sajjad; Ingrid Goebel; Naseebullah Kakar; Abdul Majeed Cheema; Christian Kubisch; Jamil Ahmad

2008-01-01

9

Influence of Consanguinity on the Pattern of Familial Aggregation of Congenital Cardiovascular Anomalies in an Outpatient Population  

Microsoft Academic Search

Background: Familial aggregation of congenital heart disease (CHD) has been well described in different populations, in particular those with a high consanguinity rate. Extensive genetic study of affected families has improved the understanding of basic genetics of different cardiac lesions. Objective: To identify the role of consanguinity as a risk factor among familial cases of CHD in a stable outpatient

Mohamed A. Seliem; Issam H. Bou-Holaigah; Nouriya Al-Sannaa

2007-01-01

10

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

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 to faulty cross-brain wiring, resulting in MRMV. PMID:25098561

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

11

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

Microsoft Academic Search

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.

C Bonaiti

1978-01-01

12

Mutations in RLBP1 associated with fundus albipunctatus in consanguineous Pakistani families  

Microsoft Academic Search

ObjectiveTo identify disease-causing mutations in two consanguineous Pakistani families with fundus albipunctatus.MethodsAffected individuals in both families underwent a thorough clinical examination including funduscopy and electroretinography. Blood samples were collected from all participating members and genomic DNA was extracted. Exclusion analysis was completed with microsatellite short tandem repeat markers that span all reported loci for fundus albipunctatus. Two-point logarithm of odds

Shagufta Naz; Shahbaz Ali; S Amer Riazuddin; Tahir Farooq; Nadeem H Butt; Ahmad U Zafar; Shaheen N Khan; Tayyab Husnain; Ian M MacDonald; Paul A Sieving; J Fielding Hejtmancik; Sheikh Riazuddin

2011-01-01

13

Novel SIL1 mutations in consanguineous Pakistani families mapping to chromosomes 5q31  

PubMed Central

Purpose To investigate the genetic basis of Marinesco-Sjogren syndrome (MSS) in consanguineous Pakistani families. Methods Two consanguineous Pakistani families with congenital cataract and muscular dystrophy were enrolled for this study. Detailed ophthalmic and systemic examination including slit lamp microscopy, electromyogram and computed tomography scans were performed to characterize the syndrome. Blood samples were collected from affected and unaffected individuals and a genome wide scan consisting of 382 polymorphic microsatellite markers was performed. Coding exons, exon-intron boundaries, 5’ UTR, and 3’ UTR of the candidate gene SIL1 residing in the linkage interval was sequenced bi-directionally. Results Clinical examination of the affected members of families 60067 and 60078 revealed features of MSS. The linked interval at chromosome 5q31 harbors SIL1. Sequencing of SIL1 in family 60067 revealed a homozygous substitution; c1240C>T, leading to a premature substitution; p.Q414X. Similarly, sequencing of SIL1 in family 60078 identified a homozygous change; c.274C>T, leading to a non conservative substitution; p.R92W. Conclusion In conclusion, our data report two novel missense mutations in two consanguineous Pakistani families affected with MSS. PMID:19471582

Amiri-Kordestani, Laleh; Kaul, Haiba; Butt, Tariq; Jiao, Xiaodong; Riazuddin, Sheikh; Hejtmancik, J. Fielding

2009-01-01

14

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

PubMed Central

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

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

2014-01-01

15

The Economics of Consanguinity  

Microsoft Academic Search

The institution of consanguineous marriage - a marriage contracted between close biological relatives - has been a basic building block of many societies in different parts of the world. This paper argues that the practice of consanguinity is closely related to the practice of dowry, and that both arise in response to an agency problem between the families of a

Sriya Iyer; Shareen Joshi

2006-01-01

16

Novel C8orf37 mutations cause retinitis pigmentosa in consanguineous families of Pakistani origin  

PubMed Central

Purpose To investigate the molecular basis of retinitis pigmentosa in two consanguineous families of Pakistani origin with multiple affected members. Methods Homozygosity mapping and Sanger sequencing of candidate genes were performed in one family while the other was analyzed with whole exome next-generation sequencing. A minigene splicing assay was used to confirm the splicing defects. Results In family MA48, a novel homozygous nucleotide substitution in C8orf37, c.244–2A>C, that disrupted the consensus splice acceptor site of exon 3 was found. The minigene splicing assay revealed that this mutation activated a cryptic splice site within exon 3, causing a 22 bp deletion in the transcript that is predicted to lead to a frameshift followed by premature protein truncation. In family MA13, a novel homozygous null mutation in C8orf37, c.555G>A, p.W185*, was identified. Both mutations segregated with the disease phenotype as expected in a recessive manner and were absent in 8,244 unrelated individuals of South Asian origin. Conclusions In this report, we describe C8orf37 mutations that cause retinal dystrophy in two families of Pakistani origin, contributing further data on the phenotype and the spectrum of mutations in this form of retinitis pigmentosa. PMID:25802487

Ravesh, Zeinab; El Asrag, Mohammed E.; Weisschuh, Nicole; McKibbin, Martin; Reuter, Peggy; Watson, Christopher M.; Baumann, Britta; Poulter, James A.; Sajid, Sundus; Panagiotou, Evangelia S.; O’Sullivan, James; Abdelhamed, Zakia; Bonin, Michael; Soltanifar, Mehdi; Black, Graeme C.M.; Din, Muhammad Amin-ud; Toomes, Carmel; Ansar, Muhammad; Inglehearn, Chris F.; Wissinger, Bernd

2015-01-01

17

The economics of consanguineous marriages  

Microsoft Academic Search

The institution of consanguineous marriage-a marriage contracted between close biological relatives-has been a basic building block of many societies in different parts of the world. This paper argues that the practice of consanguinity is closely related to the practice of dowry, and that both arise in response to an agency problem between the families of a bride and a groom.

Sriya Iyer; Shareen Joshi

2006-01-01

18

Congenital atrichia with papular lesions resulting from novel mutations in human hairless gene in four consanguineous families.  

PubMed

Congenital atrichia with papular lesions (APL; Mendelian Inheritance in Man no. 209500) is a rare form of irreversible alopecia that follows an autosomal recessive mode of inheritance. Patients with this form of alopecia show hair loss soon after birth with the development of papular lesions of keratin-filled cysts over the body. Several studies have reported sequence variants in the human hairless (HR) gene as the underlying cause of this disorder. In the present study, we have reported four consanguineous families showing features of APL. Genotyping using microsatellite markers showed mapping of all four families to the hairless (HR) gene on chromosome 8p21.1. Further, DNA sequence analysis of the HR gene revealed three novel mutations including two nonsense (p.Cys690X, p.Arg819X) and a missense (p.Pro1157Arg) in the four families. PMID:21919222

Azeem, Zahid; Wasif, Naveed; Basit, Sulman; Razak, Suhail; Waheed, Raja Amjad; Islam, Adeel; Ayub, Muhammad; Kafaitullah; Kamran-ul-hassan Naqvi, Syed; Ali, Ghazanfar; Ahmad, Wasim

2011-08-01

19

Consanguinity among the Saudi Arabian population  

Microsoft Academic Search

This study was conducted on 3212 Saudi families to investigate the prevalence of consanguineous marriages. The families were interviewed and the information on the relationship between the husband and wife was obtained. The overall rate of consanguinity shows that 57.7% of the families screened were consanguineous. The most frequent were first cousin marriages (28.4%) followed by distant relative marriages (15.2%)

M A el-Hazmi; A R al-Swailem; A S Warsy; A M al-Swailem; R Sulaimani; A A al-Meshari

1995-01-01

20

Consanguinity and child health  

Microsoft Academic Search

Marriage between close biological kin is widely regarded as genetically disadvantageous in contemporary Western societies, but consanguineous unions remain preferential in North Africa, the Middle East and large parts of Asia, with marriage between first cousins particularly popular. Many major populations also are subdivided into endogamous communities that have distinctive breeding pools. It is in these populations that intra-community marriage

Anand K. Saggar; Alan H. Bittles

2008-01-01

21

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

PubMed

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

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

2012-04-01

22

Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci  

Microsoft Academic Search

Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction.\\u000a Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR)\\u000a has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest\\u000a that in the Iranian population NS-ARMR is

Hossein Najmabadi; Mohammad Mahdi Motazacker; Masoud Garshasbi; Kimia Kahrizi; Andreas Tzschach; Wei Chen; Farkhondeh Behjati; Valeh Hadavi; Sahar Esmaeeli Nieh; Seyedeh Sedigheh Abedini; Reza Vazifehmand; Saghar Ghasemi Firouzabadi; Payman Jamali; Masoumeh Falah; Seyed Morteza Seifati; Annette Grüters; Steffen Lenzner; Lars R. Jensen; Franz Rüschendorf; Andreas W. Kuss; H. Hilger Ropers

2007-01-01

23

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

PubMed

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. PMID:25558065

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

24

Coexistence of mal de Meleda and congenital cataract in a consanguineous Tunisian family: two case reports  

PubMed Central

Introduction Mal de Meleda is a rare form of palmoplantar keratoderma, with autosomal recessive transmission. It is characterized by diffuse erythema and hyperkeratosis of the palms and soles. Recently, mutations in the ARS (component B) gene (ARS, MIM: 606119) on chromosome 8q24.3 have been identified in families with this disorder. Congenital cataract is a visual disease that may interfere with sharp imaging of the retina. Mutations in the heat-shock transcription factor 4 gene (HSF4; MIM: 602438) may result in both autosomal dominant and autosomal recessive congenital cataracts. Case presentation A Tunisian family with two female siblings aged 45 and 30 years, presented with a clinical association of mal de Meleda and congenital cataract. The two patients exhibited diffuse palmoplantar keratodermas. One of them presented with a total posterior subcapsular cataract and had a best corrected visual acuity at 1/20 in the left eye and with the right eye was only able to count fingers at a distance of one foot. The other woman had a slight posterior subcapsular lenticular opacity and her best corrected visual acuity was 8/10 in the right eye and with her left eye she was only able to count fingers at a distance of one foot. A mutational analysis of their ARS gene revealed the presence of the homozygous missense mutation C99Y and two single nucleotide polymorphisms (-55G>C and -60G>C). The splice mutation (c.1327+4A-G) within intron 12 of the HSF4 gene, which has been previously described in Tunisian families with congenital cataract, was not found in the two probands within this family. Conclusion To the best of our knowledge, such original clinical association has not been reported previously. The association of these two autosomal recessive diseases might have occurred in this family due to a high degree of inbreeding. The C99Y mutation may be specific to the Tunisian population as it has been exclusively reported so far in only three Tunisian families with mal de Meleda. PMID:20406438

2010-01-01

25

The Economics of Consanguinity  

E-print Network

The institution of consanguineous marriage - a marriage contracted between close biological relatives - has been a basic building block of many societies in different parts of the world. This paper argues that the practice of consanguinity...

Do, Quy-Toan; Iyer, Sriya; Joshi, Shareen

26

Prevalence and perceptions about consanguineous marriages among patients presenting to family physicians, in 2001 at a Teaching Hospital in Karachi, Pakistan  

Microsoft Academic Search

Aim : Consanguineous marriages are common in Pakistan despite their declining popularity in the developed world. In the present study, a questionnaire based survey was used to record the attitudes and perceptions of consanguineous marriages among the sample population. Methods : A questionnaire was developed to collect information on the acceptability of, and percep- tions about, consanguineous marriages among patients

Waris Qidwai; Iqbal Azam Syed; Faisal M Khan

2003-01-01

27

Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families.  

PubMed

Split-hand/split-foot malformation (SHFM), representing variable degree of median clefts of hands and feet, is a genetically heterogeneous group of limb malformations with seven loci mapped on different human chromosomes. However, only 3 genes (TP63, WNT10B, DLX5) for the seven loci have been identified. The study, presented here, described three consanguineous Pakistani families segregating SHFM in autosomal recessive manner. Linkage in the families was searched by genotyping microsatellite markers and mutation screening of candidate gene was performed by Sanger DNA sequencing. Clinical features of affected members of these families exhibited SHFM phenotype with involvement of hands and feet. Genotyping using microsatellite markers mapped the families to WNT10B gene at SHFM6 on chromosome 12q13.11-q13. Subsequently, sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation (c.1165_1168delAAGT) in one family and 7-bp duplication (c.300_306dupAGGGCGG) in two other families. Structure-based analysis showed a significant conformational shift in the active binding site of mutated WNT10B (p.Lys388Glufs*36), influencing binding with Fzd8. The mutations identified in the WNT10B gene extend the body of evidence implicating it in the pathogenesis of SHFM. PMID:24211389

Aziz, Abdul; Irfanullah; Khan, Saadullah; Zimri, Faridullah Khan; Muhammad, Noor; Rashid, Sajid; Ahmad, Wasim

2014-01-25

28

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

SciTech Connect

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

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

1994-07-05

29

A Discrete Event System Specification (DEVS)Based Model of Consanguinity  

Microsoft Academic Search

Consanguinity or inter-cousin marriage is a phenomenon quite prevalent in certain regions around the globe. Consanguineous parents have a higher risk of having offspring with congenital disorders. It is difficult to model large scale consanguineous parental populations because of disparate cultural issues unique to regions and cultures across the globe. Although consanguinity has previously been studied as a social problem,

Noreen Akhtar; Muaz Niazi; Farah Mustafa; Amir Hussain

2011-01-01

30

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

PubMed Central

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

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

31

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

Microsoft Academic Search

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

L Jaber; P Merlob; R Gabriel; M Shohat

1997-01-01

32

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 Central

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. PMID:24520335

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

33

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

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. PMID:24520335

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

34

Was the Darwin/Wedgwood Dynasty Adversely Affected by Consanguinity?  

NSDL National Science Digital Library

Charles Darwin, who was married to his first cousin, Emma Wedgwood, was one of the first experimentalists to demonstrate the adverse effects of inbreeding and to question the consequences of consanguineous mating. He documented the phenomenon of inbreeding depression for numerous plant species, and this caused him to worry about the health of his own children, who were often ill. To determine whether Darwin's fears were justified, we constructed a pedigree of the Darwin/Wedgwood dynasty from the large quantity of genealogical information published on these families. The inbreeding coefficients (F) computed from the pedigree show that Darwin's children were subject to a moderate level of inbreeding (F 5 0.0630), and the progeny of related families had still higher inbreeding values (e.g., F 5 0.1255 for the progeny of Henry Wedgwood, Emma Wedgwood's brother). The analysis of a sample of 25 Darwin/Wedgwood families belonging to four consecutive generations shows a statistically significant positive association between child mortality (death at or before the age of 10 years) and inbreeding coefficient detected by means of nonparametric tests (Ï? = 0.309, P = 0.040). Our findings suggest that the high childhood mortality experienced by the Darwin progeny (3 of his 10 children died at age 10 or younger) might be a result of increased homozygosity of deleterious recessive alleles produced by the consanguineous marriages within the Darwin/Wedgwood dynasty.

Tim Berra (The Ohio State University; Dept of Evolution, Ecology and Organismal Biology)

2010-05-03

35

A MEASURE OF CONSANGUINITY Fred Richman  

E-print Network

A MEASURE OF CONSANGUINITY Fred Richman of consanguinity is developed that applies to individuals with arbitrary multiple kinship connections. * * For simple relationships the consanguineal distance specializes to the civil * *degree, less two

Richman, Fred

36

Arranged marriage, consanguinity and epilepsy  

Microsoft Academic Search

Arranged marriage is where parents choose marital partners for their children. It is a norm in many parts of Asia and Middle East. A marriage is said to be consanguineous where the marriages are solemnized among persons with close biological relations. There is considerable overlap in arranged and consanguineous marriages with many cultures adopting both practices. Recent studies showed that

MM Mehndiratta; B Paul; P Mehndiratta Mehndiratta

37

Consanguineous Marriages in Iranian Folktales  

Microsoft Academic Search

Background: Using folktales we can find some aspects of social customs. Here, I show the situation of consanguineous marriages in folktales from different Iranian populations and try to compare it with the present situation of consanguineous marriages. Methods: The study includes tales from 11 different Iranian (ethnic and\\/or geographical) populations. Overall, the records of 585 marriages in 296 folktales from

Mostafa Saadat

2007-01-01

38

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

NASA Astrophysics Data System (ADS)

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.

Santos, Silvana; Bizzo, Nelio

2005-07-01

39

NKX2-5 Mutations in an Inbred Consanguineous Population: Genetic and Phenotypic Diversity  

PubMed Central

NKX2-5 mutations are associated with different forms of congenital heart disease. Despite the knowledge gained from molecular and animal studies, genotype-phenotype correlations in humans are limited by the lack of large cohorts and the incomplete assessment of family members. We hypothesized that studying the role of NKX2-5 in inbred populations with homogeneous genetic backgrounds and high consanguinity rates such as Lebanon could help closing this gap. We sequenced NKX2-5 in 188 index CHD cases (25 with ASD). Five variants (three segregated in families) were detected in eleven families including the previously documented p.R25C variant, which was found in seven patients from different families, and in one healthy individual. In 3/5 familial dominant ASD cases, we identified an NKX2-5 mutation. In addition to the heterogeneity of NKX2-5 mutations, a diversity of phenotypes occurred within the families with predominant ASD and AV block. We did in fact identify a large prevalence of Sudden Cardiac Death (SCD) in families with truncating mutations, and two patients with coronary sinus disease. NKX2-5 is thus responsible for dominant familial ASD even in consanguineous populations, and a wide genetic and phenotypic diversity is characteristic of NKX2-5 mutations in the Lebanese population. PMID:25742962

Abou Hassan, Ossama K.; Fahed, Akl C.; Batrawi, Manal; Arabi, Mariam; Refaat, Marwan M.; DePalma, Steven R.; Seidman, J. G.; Seidman, Christine E.; Bitar, Fadi F.; Nemer, Georges M.

2015-01-01

40

Consanguinity and Prereproductive Mortality in the Utah Mormon Population  

Microsoft Academic Search

To test the effects of parental consanguinity on mortality among offspring, inbreeding coefficients were estimated for 303,675 members of the Utah Mormon population who were born between 1847 and 1945. Although consanguinity has been relatively rare in this population, the large sample size permitted the identification of more than 3,500 inbred offspring. Among the offspring of unrelated parents, 13.2% died

L. B. Jorde

2001-01-01

41

Consanguinity and reproductive health among Arabs  

Microsoft Academic Search

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

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

2009-01-01

42

Consanguinity, human evolution, and complex diseases  

PubMed Central

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

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

2010-01-01

43

Consanguineous matings among Egyptian population  

Microsoft Academic Search

Consanguinity is the blood relationship that exists among individuals that descend from a common ancestor. The objectives of the study was to explore the frequency and socio-economic determinants of consanguinity in Egypt. The study was carried out using a cross-sectional approach which included 10,000 unselected couples. All couples were recruited from the prenatal, gynecologic, neonatal and pediatric clinics as well

Rabah M. Shawky; Mohammed Y. El-Awady; Solaf M. Elsayed; Ghada E. Hamadan

44

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

PubMed Central

Congenital nystagmus (NYS) is characterized by bilateral, spontaneous, and involuntary movements of the eyeballs that most commonly presents between 2 and 6 months of life. To date, 44 different FRMD7 gene mutations have been found to be etiological factors for the NYS1 locus at Xq26-q27. The aim of this study was to find the FRMD7 gene mutations in a large eleven-generation Indian pedigree with 71 members who are affected by NYS. Mutation analysis of the entire coding region and splice junctions of the FRMD7 gene revealed a novel missense mutation, c.A917G, predicts a substitution of Arg for Gln at codon 305 (Q305R) within exon 10 of FRMD7. The mutation was detected in hemizygous males, and in homozygous and heterozygous states in affected female members of the family. This mutation was not detected in unaffected members of the family or in 100 unrelated control subjects. This mutation was found to be at a highly conserved residue within the FERM-adjacent domain in affected members of the family. Structure prediction and energetic analysis of wild-type FRMD7 compared with mutant (Q305R) revealed that this change in amino acid led to a change in secondary structure predicted to be an energetically unstable protein. The present study represents the first confirmation of FRMD7 gene mutations in a multigenerational Indian family and expands the mutation spectrum for this locus. PMID:22490987

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

2012-01-01

45

SocioEconomic Epidemiology of Consanguineous Matings in the Saudi Arabian Population  

Microsoft Academic Search

The rate and socio-economic factors associated with consanguineous matings among 4498 Saudi families living in Riyadh have been evaluated. The incidence of consanguinity in the urban Saudi population is unusually high, has been common among Saudi people during the past decades and has not changed significantly even among the younger generation. There is a statistically significant relationship between educational level

Simin Saedi-Wong; Abdul Rahman Al-Frayh; Henry Y. H. Wong

1989-01-01

46

Association studies in consanguineous populations  

SciTech Connect

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.

Genin, E.; Clerget-Darpous, F. [Institut National d`Etudes Demographiques, Paris (France)

1996-04-01

47

The Influence of the Wahlund Effect on the Consanguinity Hypothesis: Consequences for Recessive Disease Incidence in a Socially Structured Pakistani Population  

Microsoft Academic Search

Background\\/Aims: Standard population genetic theory predicts that the relative risk of inheriting recessive disorders between consanguineous and non-consanguineous populations can be manyfold. However, it is rarely considered that consanguineous populations might be composites of socially defined endogamous and genetically differentiated subpopulations. A recent study of a British Pakistani population found evidence to suggest that extended families (biraderi) could contribute significantly

Andrew D. J. Overall

2009-01-01

48

Parental responses to consanguinity and genetic disease in Saudi Arabia  

Microsoft Academic Search

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

Catherine Panter-Brick

1991-01-01

49

Consanguinity-associated kidney diseases in Lebanon: an epidemiological study  

Microsoft Academic Search

Consanguineous marriages are common in many countries of the Middle East including Lebanon. Their impact on the repartition of kidney diseases and on the risk for familial nephritis is not known. We surveyed all of the dialysis centers in Lebanon. Nine hundred and twenty-five (925) patients and their private physicians were asked to answer a questionnaire. More than half of

A Barbari; A Stephan; M Masri; A Karam; S Aoun; J El Nahas; J Bou Khalil

2003-01-01

50

The impact of consanguinity worldwide.  

PubMed

Consanguineous marriages have been practiced for hundreds of years in many parts of the world. The rate of congenital malformations among the offspring is 2.5 times higher than that among the offspring of unrelated parents, mainly due to the expression of autosomal-recessive disorders, and hospitalization for these reasons causes a major financial burden. An increase in sterility and in the rates of abortion, stillbirths, perinatal losses and neonatal deaths has been reported by some authors but not by others. It is generally accepted that the advantages of consanguinity outweigh the disadvantages; however, strategies for reducing the burden require a unique approach as discussed in this article. PMID:15178982

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

1998-01-01

51

A MEASURE OF CONSANGUINITY Fred Richman  

E-print Network

A MEASURE OF CONSANGUINITY Fred Richman New Mexico State University, Las Cruces NM 88003 Abstract. A natural numerical measure of consanguinity is developed that applies to individuals with arbitrary multiple kinship connections. For simple relationships the consanguineal distance specializes to the civil

Richman, Fred

52

Recurrent early pregnancy loss and consanguinity  

Microsoft Academic Search

The present authors have studied the possible relationship between recurrent miscarriage and consanguinity in the Qatari population, where the prevalence of first cousin marriage is 47%. The maternal characteristics and obstetric outcome of 92 Qatari women in a consanguineous relationship and with an obstetrical history of three or more early pregnancy losses were compared with those of 92 non-consanguineous women

Fawaz Amin Saad; Eric Jauniaux

2002-01-01

53

On Some Novel Aspects of Consanguineous Marriages  

Microsoft Academic Search

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

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

2011-01-01

54

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

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

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

2013-01-01

55

Is There a Significant Trend in Prevalence of Consanguineous Marriage in Tehran? A Review of Three Generations  

Microsoft Academic Search

Consanguineous marriage is a common practice in Iran. The present study surveyed the trend in consanguineous marriage across\\u000a three generations of Iranians. Index cases, consisting of 400 individuals attending the diabetes and osteoporosis clinic in\\u000a Shariati Hospital, were interviewed. Data on consanguinity status for 1789 marriages within the index cases’ families were\\u000a obtained. Generation 1 consisted of marriages contracted before

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

2009-01-01

56

The Perils of SNP Microarray Testing: Uncovering Unexpected Consanguinity  

PubMed Central

Background While single nucleotide polymorphism (SNP) chromosomal microarrays identify areas of small genetic deletions/duplications, they can also reveal regions of homozygosity indicative of consanguinity. As more non-geneticists order SNP microarrays, they must prepare for the potential ethical, legal and social issues that result from revelation of unanticipated consanguinity. Patient An infant with multiple congenital anomalies underwent SNP microarray testing. Results The results of the SNP microarray revealed several large regions of homozygosity that indicated identity by descent most consistent with a second or third degree relative mating (e.g., uncle/ niece, half brother/sister, first cousins). Mother was not aware of the test's potential to reveal consanguinity. When informed of the test results, she reluctantly admitted to being raped by her half-brother around the time of conception. Conclusions During the pre-testing consent process, providers should inform parents that SNP microarray testing could reveal consanguinity. Providers must also understand the psychological implications, as well as the legal and moral obligations, that accompany SNP microarray results that indicate consanguinity. PMID:23827427

Tarini, Beth A.; Konczal, Laura; Goldenberg, Aaron J.; Goldman, Edward B.; McCandless, Shawn E.

2013-01-01

57

Asteroid families classification: Exploiting very large datasets  

NASA Astrophysics Data System (ADS)

The number of asteroids with accurately determined orbits increases fast, and this increase is also accelerating. The catalogs of asteroid physical observations have also increased, although the number of objects is still smaller than in the orbital catalogs. Thus it becomes more and more challenging to perform, maintain and update a classification of asteroids into families. To cope with these challenges we developed a new approach to the asteroid family classification by combining the Hierarchical Clustering Method (HCM) with a method to add new members to existing families. This procedure makes use of the much larger amount of information contained in the proper elements catalogs, with respect to classifications using also physical observations for a smaller number of asteroids. Our work is based on a large catalog of high accuracy synthetic proper elements (available from AstDyS), containing data for >330,000 numbered asteroids. By selecting from the catalog a much smaller number of large asteroids, we first identify a number of core families; to these we attribute the next layer of smaller objects. Then, we remove all the family members from the catalog, and reapply the HCM to the rest. This gives both satellite families which extend the core families and new independent families, consisting mainly of small asteroids. These two cases are discriminated by another step of attribution of new members and by merging intersecting families. This leads to a classification with 128 families and currently 87,095 members. The number of members can be increased automatically with each update of the proper elements catalog; changes in the list of families are not automated. By using information from absolute magnitudes, we take advantage of the larger size range in some families to analyze their shape in the proper semimajor axis vs. inverse diameter plane. This leads to a new method to estimate the family age, or ages in cases where we identify internal structures. The analysis of the plot above evidences some open problems but also the possibility of obtaining further information of the geometrical properties of the impact process. The results from the previous steps are then analyzed, using also auxiliary information on physical properties including WISE albedos and SDSS color indexes. This allows to solve some difficult cases of families overlapping in the proper elements space but generated by different collisional events. The families formed by one or more cratering events are found to be more numerous than previously believed because the fragments are smaller. We analyze some examples of cratering families (Massalia, Vesta, Eunomia) which show internal structures, interpreted as multiple collisions. We also discuss why Ceres has no family.

Milani, Andrea; Cellino, Alberto; Kneževi?, Zoran; Novakovi?, Bojan; Spoto, Federica; Paolicchi, Paolo

2014-09-01

58

Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome  

Microsoft Academic Search

Mutations in myosin XVA are responsible for the shaker 2 (sh2) phenotype in mice and nonsyndromic autosomal recessive profound hearing loss DFNB3 on chromosome 17p11.2. We have ascertained seven families with profound congenital hearing loss from Pakistan and India with evidence of linkage to DFNB3 at 17p11.2. We report three novel homozygous mutations in MYO15A segregating in three of these

Nikki Liburd; Manju Ghosh; Saima Riazuddin; Sadaf Naz; Shaheen Khan; Zubair Ahmed; Sheikh Riazuddin; Yong Liang; Puthezhath S. N. Menon; Tenesha Smith; Ann C. M. Smith; Ken-Shiung Chen; James R. Lupski; Edward R. Wilcox; Lorraine Potocki; Thomas B. Friedman

2001-01-01

59

Consanguinity in South America: Demographic Aspects  

Microsoft Academic Search

A sample of 53,552 nonmalformed liveborn infants was ascertained by the Latin-American Collaborative Study of Congenital Malformations between 1967 and 1996. The mean consanguinity rate was 0.96%, with significantly higher values in Brazil and Venezuela, and lower in Argentina. Low paternal education and occupation levels were positively associated with consanguinity. First-cousin matings represented almost half of all consanguineous couples. The

Rosa Liascovich; Mónica Rittler; Eduardo E. Castilla

2001-01-01

60

Consanguinity and reproductive health among Arabs  

PubMed Central

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

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

2009-01-01

61

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

Microsoft Academic Search

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

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

1990-01-01

62

Consanguineous matings in the Egyptian population  

Microsoft Academic Search

A total of 26 554 Egyptians was ascertained to study the incidence of consanguineous marriages. They were of different ages, different socioeconomic standards, and from different areas. There were 7646 from urban areas, 11 280 from suburban areas, and 7628 from rural areas. The incidence of consanguineous matings in the general population was found to be 28.96% with an average

M Hafez; H El-Tahan; M Awadalla; H El-Khayat; A Abdel-Gafar; M Ghoneim

1983-01-01

63

Consanguineous marriages in diocesis of Brno, Czechoslovakia  

Microsoft Academic Search

The frequency of consanguineous marriages in our country which has been evaluated with regard to the corresponding time period does not differ on the whole from the data given for the European populations. The relatively higher frequency of consanguineous marriages in the years before the World War II was due to the greater endogamy among the German inhabitans especially in

M. Zahálková; A. Preis

1970-01-01

64

Reproductive Behavior and Health in Consanguineous Marriages  

Microsoft Academic Search

In many regions of Asia and Africa, consanguineous marriages currently account for approximately 20 to 50% of all unions, and preliminary observations indicate that migrants from these areas continue to contract marriages with close relatives when resident in North America and Western Europe. Consanguinity is associated with increased gross fertility, due at least in part to younger maternal age at

Alan H. Bittles; William M. Mason; Jennifer Greene; N. Appaji Rao

1991-01-01

65

A Community Genetics Perspective on Consanguineous Marriage  

Microsoft Academic Search

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

A. H. Bittles

2008-01-01

66

A novel GEFS+ locus on 12p13.33 in a large Roma family.  

PubMed

We report a clinical and genetic follow-up study of a large consanguineous family from an endogamous Roma/Gypsy sub-isolate, where previous analyses have been inconclusive. Detailed clinical information was collected through extensive field work, repeat interviews and electrophysiological and neuroimaging investigations on 18 affected subjects. The phenotype is compatible with GEFS+, with some unusual features, e.g. GTCS persisting into late adult life and high frequency of focal epilepsy. Updated genealogical information, a dense SNP genome scan and linkage analysis identified a novel GEFS+ locus on 12p13.33, where 13 affected individuals from two branches of the kindred shared an identical haplotype. This haplotype was not found in the 3rd branch or in the remaining 21 Roma epilepsy families in our collection. Genetic heterogeneity and evidence of bilineality were found despite the inbreeding and endogamous nature of the family and population of origin. These data add to the growing evidence of lack of founder effect and significant genetic heterogeneity in epilepsy in the Roma/Gypsy population. Sequencing of the coding regions of three genes linked to neurotransmitter transport and release, SLC6A12, SLC6A13 and ERC1, on 12p did not identify a causative mutation. PMID:21917424

Morar, Bharti; Zhelyazkova, Sashka; Azmanov, Dimitar N; Radionova, Melania; Angelicheva, Dora; Guergueltcheva, Velina; Kaneva, Radka; Scheffer, Ingrid E; Tournev, Ivailo; Kalaydjieva, Luba; Sander, Josemir W

2011-11-01

67

Consanguineous matings in the Egyptian population.  

PubMed Central

A total of 26 554 Egyptians was ascertained to study the incidence of consanguineous marriages. They were of different ages, different socioeconomic standards, and from different areas. There were 7646 from urban areas, 11 280 from suburban areas, and 7628 from rural areas. The incidence of consanguineous matings in the general population was found to be 28.96% with an average inbreeding coefficient of 0.010, which could be considered high. The highest incidence was that in the rural areas. First cousin marriages occurred more often than the other types of consanguinity. PMID:6842535

Hafez, M; El-Tahan, H; Awadalla, M; El-Khayat, H; Abdel-Gafar, A; Ghoneim, M

1983-01-01

68

Consanguinity and Its Sociodemographic Differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan  

PubMed Central

ABSTRACT 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

Jabeen, Nazish

2014-01-01

69

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

PubMed

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

Jabeen, Nazish; Malik, Sajid

2014-06-01

70

Consanguinity, genetic disorders and malformations in the Iranian population  

Microsoft Academic Search

The present study focuses on the effect of parental consanguinity on genetic disorders in the Iranian population, which is predominantly Muslim and where consanguineous marriages are quite common. Data were collected from three genetic centers from different areas of Tehran. Out of 800 affected subjects nearly 44% were born to consanguineous parents. While 37.8% of them were born out of

Roya Mokhtari; Amrita Bagga

71

Assessment of Association between Consanguinity and Fertility in Asian Populations  

Microsoft Academic Search

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

Rafat Hussain; Alan H. Bittles

2004-01-01

72

Consanguine Calculations Input File: blood.in  

E-print Network

1 of 20 Problem A+ Consanguine Calculations Input File: blood.in Every person's blood has 2 markers in a particular ABO blood type for that person. Combination ABO Blood Type AA A AB AB AO A BB B BO B OO O Likewise, every person has two alleles for the blood Rh factor, represented by the characters + and -. Someone who

California at Berkeley, University of

73

Genetic sperm defects and consanguinity  

Microsoft Academic Search

BACKGROUND: The existence of a genetic component to human infertility has been suggested, although neither the specific abnormalities involved, nor their genetic mechanism of transmission, are currently defined. We have examined, by transmission electron microscopy (TEM), ejaculate from 1600 males with fertility problems. Among the subjects studied, we focused on a group of patients whose family histories revealed different degrees

B. Baccetti; S. Capitani; G. Collodel; G. Di Cairano; L. Gambera; E. Moretti; P. Piomboni

2001-01-01

74

Autosomal recessive anhidrotic ectodermal dysplasia in a large Moroccan family.  

PubMed Central

We studied a large Moroccan family in which anhidrotic ectodermal dysplasia is transmitted as an autosomal recessive trait. Fourteen family members, both males and females, were affected and they all had a common ancestor. Linkage analysis by homozygosity mapping in this family will permit the gene localisation of this rare form of anhidrotic ectodermal dysplasia. Images PMID:9863606

Kabbaj, K; Baala, L; Chhoul, H; Sefiani, A

1998-01-01

75

Role of Consanguinity in Congenital Neurosensory Deafness  

Microsoft Academic Search

Congenital deafness affects the speech and psychosocial development of the affected child. It could be syndromic or non-syndromic depending on the presence or absence of the associated manifestations. Among various etiological factors described for deafness, consanguinity is an established high risk etiological factor. A prospective study was carried out in 1076 children in the age group of 0-14years attending Government

M. V. V. Reddy; L. Hema Bindu; P. P. Reddy; P. Usha Rani

76

Birth Defects and Parental Consanguinity in Norway  

Microsoft Academic Search

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

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

77

Consanguinity-related hyperdontia: An orthopantomographic study  

PubMed Central

Background: The aim of this retrospective study was to describe the distribution of the non-syndromal supernumerary teeth (NSST) in a population of patients who attended the clinics of Riyadh Colleges of Dentistry and Pharmacy (RCsDP), Riyadh, Saudi Arabia. Materials and Methods: The study reviewed 1521 panoramic radiographs of Saudi and non-Saudi subjects who attended RCsDP clinic from November 2009 to November 2010. The data were analyzed using the Statistical Package for Social Sciences, utilizing Chi-square. Results: Eighteen (1.2%) patients were found to have NSST, comprising twelve males (66.7%), and six females (33.3%). The most common supernumerary teeth (ST) were the pre-molars six cases (33.3%), followed by the mesiodens, five cases (27.8%). The canines and distomolars three cases (16.6%) each respectively, while the least were the lateral incisors and paramolars of the two cases (11.1%) each. Conclusion: Consanguinity appeared to have a role in the development of hyperdontia in Saudi population because 13 cases (72.2%) out of 18 cases had consanguineous parents, while all patients having consanguineous parents had eumorphic ST. PMID:24379860

Shokry, Shereen M.; Alenazy, Mohammed S.

2013-01-01

78

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

PubMed

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

Al-Arrayed, Shaikha; Hamamy, Hanan

2012-05-01

79

Consanguinity and Birth Defects in the Jerusalem Perinatal Study Cohort  

Microsoft Academic Search

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

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

2008-01-01

80

Chromosome abnormality rate among Iranian patients with idiopathic mental retardation from consanguineous marriages  

PubMed Central

Introduction Mental retardation (MR) has heterogeneous aetiology mostly with genetic causes. Chromosomal aberrations are one of the most common causes of MR. Reports on chromosome abnormality rate among consanguineous families are sparse. In order to identify the chromosome abnormality rate in idiopathic mental retardation from consanguineous marriages, a total of 322 Iranian families with positive family history for MR were investigated in the Genetics Research Center. Material and methods In the majority of families (92%) at least two sibs were affected with MR and none had specific chromosomal syndromes such as Down syndrome. Standard cytogenetic techniques using high resolution GTG banding were carried out on all the patients. Results The overall chromosome abnormality rate contributing to mental retardation was 1.24% (4 cases), which comprised 46,XY,der(18)t(4;18)(q31.1;q23)mat; 45,XY,-21,-22,+der(22)t(21;22)(q21.1;q13.33)mat; 46,XY,rec(2)dup(2p)inv(2)(p25.1q37.3)pat, and 46,XY,der(11)t(10;11)(q25.2;q25)pat. Conclusions Although the most likely genetic cause of mental retardation in patients with consanguineous parents is autosomal recessive, the fact that 1.24% of our patients had chromosomal abnormalities emphasizes the importance of cytogenetic investigation as the first laboratory genetic tests for all MR patients. To our knowledge, this is the first report on the rate of chromosome abnormality among patients with idiopathic mental retardation from consanguineous marriages. PMID:22291774

Behjati, Farkhondeh; Ghasemi Firouzabadi, Saghar; Kahrizi, Kimia; Kariminejad, Roxana; Bagherizadeh, Iman; Ansari, Javad; Fallah, Masoumeh; Mojtahedi, Forough; Darvish, Hossein; Bahrami Monajemi, Gholamreza; Abedini, S. Sedigheh; Jamali, Payman; Mojahedi, Faezeh; Zadeh-Vakili, Azita; Najmabadi, Hossein

2011-01-01

81

Little Brother Joins the Large Family  

NASA Astrophysics Data System (ADS)

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

2006-12-01

82

Parental responses to consanguinity and genetic disease in Saudi Arabia.  

PubMed

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. PMID:1776043

Panter-Brick, C

1991-01-01

83

Consanguinity decreases risk of breast cancer – cervical cancer unaffected  

Microsoft Academic Search

Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring

S Denic; A Bener

2001-01-01

84

Consanguineous marriages in the province of Antalya, Turkey  

Microsoft Academic Search

To assess the trends in the frequency and the medical effects of consanguinity in the south coast of Turkish population using local and national data in the last 11 years. This cross-sectional study was carried out in Manavgat province, which is a major tourism center on the Mediterranean coast of Turkey. The authors studied consanguineous marriages in rural and urban population

Ö. M. Alper; H. Erengin; A. E Manguo?lu; T. Bilgen; Z. Çetin; N. Dedeo?lu; G. Lüleci

2004-01-01

85

Does consanguinity lead to decreased incidence of breast cancer?  

Microsoft Academic Search

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

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

2010-01-01

86

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

Microsoft Academic Search

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

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

2006-01-01

87

Ancestral Consanguinity and Mortality Among Three Endogamous Populations of Chittoor District, Andhra Pradesh, India  

Microsoft Academic Search

Consanguineous marriages have been practiced around the globe by many societies from time immemorial, particularly in South India. Consanguineous marriages play a major role in the health of a population, and diseases leading to mortality of the progeny are a consequence of detrimental recessive genes. To evaluate the effects of ancestral consanguinity on mortality in relation to consanguineous marriage, we

T. P. K. Reddy; K. K. Reddy; P. G. Reddy

2007-01-01

88

INFLUENCE OF CONSANGUINITY ON PRODUCTIVE INDICES OF CC21 PIGS  

Microsoft Academic Search

SUMMARY The BLUP animal model methodology was employed for determining the influence of levels of consanguinity on productive performance of CC21 pigs. A sample of 9 672 individuals sons from 951 mothers and 278 fathers from the Genetic Centre \\

C. M. Abeledo; Dianelys González; M. Gutiérrez; F. J. Diéguez; Isabel Santana; Sonia Hernández

89

Does consanguinity affect the severity of pre-eclampsia?  

Microsoft Academic Search

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

Francis L. Badria; Z. O. Amarin

2003-01-01

90

New Sequences with Low Correlation and Large Family Size  

NASA Astrophysics Data System (ADS)

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

Zeng, Fanxin

91

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

PubMed

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. PMID:14621249

Sueyoshi, Shuji; Ohtsuka, Ryutaro

2003-10-01

92

Airfoil family design for large offshore wind turbine blades  

NASA Astrophysics Data System (ADS)

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

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

2014-06-01

93

Severe prognosis in a large family with hypokalemic periodic paralysis.  

PubMed

Hypokalemic periodic paralysis (HypoPP) is a channel disorder caused primarily by mutations in the human skeletal muscle alpha1 subunit (CACNA1S) of the dihydropyridine-sensitive calcium channel. Molecular, clinical, and biochemical studies were aimed at establishing genotype/phenotype correlations in a large Italian family affected by a severe form of HypoPP. Whereas patients with HypoPP usually show a normal life span, in this family three male patients died young, one of them from anesthetic complications resembling malignant hyperthermia. Our patients carried the c1583G>A genetic lesion (R528H), which has been associated with a mild phenotype and with incomplete penetrance in women. Surprisingly, the R528H amino acid substitution in the family presented here correlated with an unfavorable prognosis in both male and female patients. We conclude that genetic characterization is an important requirement to alert physicians about the management of similar patients, especially when anesthesia is considered. PMID:12548523

Caciotti, Anna; Morrone, Amelia; Domenici, Raffaele; Donati, Maria Alice; Zammarchi, Enrico

2003-02-01

94

Complex genetic background in a large family with Brugada syndrome  

PubMed Central

Abstract The Brugada syndrome (BrS) is an inherited arrhythmia characterized by ST?segment elevation in V1–V3 leads and negative T wave on standard ECG. BrS patients are at risk of sudden cardiac death (SCD) due to ventricular tachyarrhythmia. At least 17 genes have been proposed to be linked to BrS, although recent findings suggested a polygenic background. Mutations in SCN5A, the gene coding for the cardiac sodium channel Nav1.5, have been found in 15–30% of index cases. Here, we present the results of clinical, genetic, and expression studies of a large Iranian family with BrS carrying a novel genetic variant (p.P1506S) in SCN5A. By performing whole?cell patch?clamp experiments using HEK293 cells expressing wild?type (WT) or p.P1506S Nav1.5 channels, hyperpolarizing shift of the availability curve, depolarizing shift of the activation curve, and hastening of the fast inactivation process were observed. These mutant?induced alterations lead to a loss of function of Nav1.5 and thus suggest that the p.P1506S variant is pathogenic. In addition, cascade familial screening found a family member with BrS who did not carry the p.P1506S mutation. Additional next generation sequencing analyses revealed the p.R25W mutation in KCNH2 gene in SCN5A?negative BrS patients. These findings illustrate the complex genetic background of BrS found in this family and the possible pathogenic role of a new SCN5A genetic variant. PMID:25626866

Saber, Siamak; Amarouch, Mohamed?Yassine; Fazelifar, Amir?Farjam; Haghjoo, Majid; Emkanjoo, Zahra; Alizadeh, Abolfath; Houshmand, Massoud; Gavrilenko, Alexander V.; Abriel, Hugues; Zaklyazminskaya, Elena V.

2015-01-01

95

Complex genetic background in a large family with Brugada syndrome.  

PubMed

The Brugada syndrome (BrS) is an inherited arrhythmia characterized by ST-segment elevation in V1-V3 leads and negative T wave on standard ECG. BrS patients are at risk of sudden cardiac death (SCD) due to ventricular tachyarrhythmia. At least 17 genes have been proposed to be linked to BrS, although recent findings suggested a polygenic background. Mutations in SCN5A, the gene coding for the cardiac sodium channel Nav1.5, have been found in 15-30% of index cases. Here, we present the results of clinical, genetic, and expression studies of a large Iranian family with BrS carrying a novel genetic variant (p.P1506S) in SCN5A. By performing whole-cell patch-clamp experiments using HEK293 cells expressing wild-type (WT) or p.P1506S Nav1.5 channels, hyperpolarizing shift of the availability curve, depolarizing shift of the activation curve, and hastening of the fast inactivation process were observed. These mutant-induced alterations lead to a loss of function of Nav1.5 and thus suggest that the p.P1506S variant is pathogenic. In addition, cascade familial screening found a family member with BrS who did not carry the p.P1506S mutation. Additional next generation sequencing analyses revealed the p.R25W mutation in KCNH2 gene in SCN5A-negative BrS patients. These findings illustrate the complex genetic background of BrS found in this family and the possible pathogenic role of a new SCN5A genetic variant. PMID:25626866

Saber, Siamak; Amarouch, Mohamed-Yassine; Fazelifar, Amir-Farjam; Haghjoo, Majid; Emkanjoo, Zahra; Alizadeh, Abolfath; Houshmand, Massoud; Gavrilenko, Alexander V; Abriel, Hugues; Zaklyazminskaya, Elena V

2015-01-01

96

Examining BCL-2 family function with large unilamellar vesicles.  

PubMed

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

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

2012-01-01

97

Awareness about problems associated with consanguineous marriages: Survey among Israeli Arab adolescents  

Microsoft Academic Search

PurposeTo evaluate the level of knowledge among adolescents about the issues associated with consanguinity, because consanguineous marriages are widely practiced among Arabs, and are associated with an increased incidence of congenital malformations.

Lutfi Jaber; Orli Romano; Gabrielle J. Halpern; Irit Livne; Manfred Green; Tamy Shohat

2005-01-01

98

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

PubMed

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. PMID:24308209

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

2013-09-01

99

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

PubMed

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

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

2013-10-01

100

Consanguinity and advanced maternal age as risk factors for reproductive losses in Alexandria, Egypt  

Microsoft Academic Search

Background: Consanguinity has been a long-standing social habit among Egyptians. Estimates of consanguinity ratios in different parts of Egypt ranged from 29 to 50%. This study aimed at delineating the role of consanguinity and advanced maternal age on reproductive losses in Alexandria, Egypt. Methods: A case-control study, on 730 couples with history of reproductive losses and 2081 normal couples, was

Mohamed M. Mokhtar; Moataz M. Abdel-Fattah

2001-01-01

101

Parental consanguinity and susceptibility to drug abuse among offspring, a case–control study  

Microsoft Academic Search

Consanguineous marriage is the union of individuals having at least one common ancestor. It is well established that consanguinity is a potential risk factor for many adverse health outcome of offspring. In the present case–control study we tested the hypothesis of an association between parental consanguinity marriages and risk of offspring substance abuse. The study was performed in Shiraz (Fars

Mostafa Saadat; Roghayyeh Vakili-Ghartavol

2010-01-01

102

E-Mail karger@karger.com Population Aspects of Consanguinity  

E-print Network

E-Mail karger@karger.com Population Aspects of Consanguinity Hum Hered 2014;77:37­48 DOI: 10 estimates in populations and geographic regions with known high levels of consanguinity or genetic isolation from Africa. For the small number of populations with specific consanguinity estimates, we find

Rosenberg, Noah

103

Inbreeding in Gredos Mountain Range (Spain): Contribution of Multiple Consanguinity and Intervalley Variation  

Microsoft Academic Search

2 Abstract The present paper examines consanguineous marriages occur- ring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tiétar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity

V. FUSTER; A. M. Jimenez; S. E. Colantonio

2001-01-01

104

Inbreeding in Gredos Mountain Range (Spain): Contribution of Multiple Consanguinity and Intervalley Variation  

Microsoft Academic Search

The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tiétar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From

V. Fuster; A. M. Jiménez; S. E. Colantonio

2011-01-01

105

Consanguinity and Ocular Genetic Diseases in South India: Analysis of a Five-Year Study  

Microsoft Academic Search

Objective: Consanguineous marriage is a widely practised social custom in Asia and northern Africa. In south India, Dravidian Hindus have contracted consanguineous marriages for over 2,000 years. In the present study, the influence of consanguinity on the prevalence of visual disorders was examined in patients attending a specialist genetic eye clinic. Subjects and Methods: A total of 2,335 patients attending

G. Kumaramanickavel; B. Joseph; A. Vidhya; T. Arokiasamy; N. Shridhara Shetty

2002-01-01

106

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

PubMed Central

Hypocalcemia and hyperphosphatemia with low/normal parathyroid hormone (PTH) levels can be observed in hypoparathyroidism (HP), a disorder that may follow an autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. Similar biochemical changes are also observed in pseudohypoparathyroidism (PHP) type Ia and Ib, but affected patients usually show elevated PTH levels indicative of hormonal resistance. Features of Albright’s hereditary osteodystrophy (AHO) are typically not observed in patients affected by familial forms of PHP-Ib, which are most frequently caused by maternally inherited, heterozygous microdeletions within STX16 and are associated with isolated loss of methylation at GNAS exon A/B. We established the molecular defect in two children of consanguineous Turkish parents, who presented with hypocalcemia, hyperphosphatemia, and low 25-OH vitamin D levels, but initially normal or only mildly elevated PTH levels, i.e. findings that do not readily exclude HP. After normalizing serum magnesium levels, hypocalcemia and hyperphosphatemia persisted, and PTH levels increased, suggesting PTH-resistance rather than PTH-deficiency. Because of the absence of AHO and parental consanguinity, an AR form of PHP-Ib appeared plausible, which had previously been suggested for sporadic cases. However, loss of GNAS methylation was restricted to exon A/B, which led to the identification of the 3-kb STX16 microdeletion. The same mutation was also detected in the healthy mother, who did not show any GNAS methylation abnormality, indicating that her deletion resides on the paternal allele. Our findings emphasize the importance of considering a parentally imprinted, autosomal dominant disorder even if consanguinity suggests an autosomal recessive mode of inheritance. PMID:20538864

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

2010-01-01

107

A large family of filled skutterudites stabilized by electron count.  

PubMed

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

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

2015-01-01

108

A large family of filled skutterudites stabilized by electron count  

NASA Astrophysics Data System (ADS)

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

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

2015-03-01

109

Dysmorphic Features, Consanguinity and Cytogenetic Pattern of Congenital Heart Diseases: a pilot study from Mansoura Locality, Egypt  

PubMed Central

Background: Congenital heart diseases (CHD) constitute a common cause of birth defects with a multifactorial inheritance background. Objectives: to check for the dysmorphic features, consanguinity and cytogenetic pattern that may be associated with congenital heart disease in Egyptian cases from Mansoura, Egypt. Methods: This work is a pilot prospective controlled study including randomly selected 69 cases affected with congenital heart disease recruited from the Pediatric Cardiology Department, Mansoura University, Egypt. These cases were compared to 500 normal children of matched age and sex taken from the same locality serving as a control group. Complete history taking, clinical examination for dysmorphic features as well as cardiac examination were carried out for all subjects. Furthermore, cases were evaluated by Echocardiography and cytogenetic studies. Results: Egyptian children affected with CHD were significantly associated with positive family history of CHD, perinatal history of maternal diseases or drug intake during pregnancy and positive parental consanguinity (odds ratio = 10.5, 7.6 and 3.1 respectively). Significant associated dysmorphic features included ear anomalies, eye anomalies, cleft lip, polydactyly and cleft palate (odds ratio = 217.6, 176.6, 68.7 and 37.07 respectively). Seven cases (10.1%) had chromosomal aberrations and were associated with dysmorphic features. Conclusion: Risk of CHD increased with positive family history and consanguinity. Cytogenetic studies added to dysmorphic features seem to have an important clue for early diagnosis of CHD. Key words: Heart disease, risk factors, dysmorphism, Egypt PMID:21475491

Settin, Ahmad; AlMarsafawy, Hala; AlHussieny, Ahmad; Dowaidar, Moataz

2008-01-01

110

Consanguineous Marriages in the Sikh Community of Swat, NWFP, Pakistan  

Microsoft Academic Search

Marriages among the Sikh minority of the Districts of Swat, Bunair and Shangla (NWFP, Pakistan) were studied where the frequency of consanguineous marriages was found to be 21%. Marriages with distant relatives were 29.4% in the population. The inbreeding coefficient for the population was calculated to be 0.0127. Only three types of first cousin marriages (MSD, MBD and FSD) were

Abdul Wahab; Mahmud Ahmad

2005-01-01

111

A research of consanguinity in Japanese young couples  

Microsoft Academic Search

In the past, the rate of consanguineous marriage in Japanese population was high (6~ in Hiroshima and Nagasaki, and 4~ in Tokyo) (Schull and Neel, 1965). However, it has decreased rapidly during the last two decades. The nationwide survey (Imaizumi et al., 1975) showed that the mean rate of first cousin marriage was 0.86~ among young couples who got married

Yuri Hosoda; Keiko Fujiki; Akira Nakajima

1983-01-01

112

Religious endogamy and consanguinity in marriage patterns in Beirut, Lebanon  

Microsoft Academic Search

Marriage patterns are analyzed in a sample of 750 recently married couples from the city of Beirut. The data provide evidence for a notable religious endogamy (88 per cent of the marriages occur within the same religious community, whereas the expected proportion is 34 per cent), and isolation of Muslims and Christians, with some migration occurring inside each group. Consanguineous

Myriam Klat; Adèle Khudr

1986-01-01

113

Letters to the Editor CONSANGUINITY AND HETEROGENEITY: CYSTIC FIBROSIS  

E-print Network

Letters to the Editor CONSANGUINITY AND HETEROGENEITY: CYSTIC FIBROSIS NEED NOT BE HOMOGENEOUS fibrosis (CF), Romeo et al. [1] conclude that "CF is homo- geneously determined by mutations at a single, ET AL.: Incidence in Italy, genetic heterogeneity, and segregation analysis of cystic fibrosis. Am J

Botstein, David

114

Consanguinity, caste and deaf-mutism in Punjab, 1921.  

PubMed

The effects of religion, population sub-division and geography on the prevalence of deaf-mutism were investigated using information collected in the 1921 Census of Punjab. The total sample size was 9.36 million, and comprised data on thirteen Hindu castes, seventeen Muslim biraderis and two Sikh castes. A two-way analysis of variance comparing males in Hindu castes in which consanguineous marriage was prohibited, with males in Muslim biraderis which favoured first cousin marriage, indicated major differences with respect to the patterns of deaf-mutism within each religion. In the Muslim population 9.1% of the relative variation in the prevalence of deaf-mutism was inter-biraderi, 36.8% between geographical regions, and 48.8% an interaction between biraderi and region, whereas among Hindus 46.8% of the observed variation was inter-caste, 12.8% inter-region and 33.6% due to caste region interaction. From a wider disease perspective the results obtained with the Hindu community indicate the significant genetic differentiation associated with caste endogamy. As the overwhelming majority of Hindu marriages continue to be within-caste, it can be predicted that similar levels of inter-caste differences in disease frequency currently exist. By comparison, the lower level of inter-biraderi variation among Muslims is probably indicative of the dissolution of pre-existing caste boundaries and the resultant gene pool mixing that followed the large-scale conversion of Hindus to Islam during Muslim rule in North India from the 13th to the 19th centuries. PMID:15030017

Bittles, A H; Sullivan, S G; Zhivotovsky, L A

2004-03-01

115

Large quinacrine study comes under fire from family planners.  

PubMed

A large study among 31,781 women, in 24 provinces of Vietnam, who underwent nonsurgical female sterilization via insertion of 2 doses of quinacrine 30 days apart has various flaws, according to many family planning specialists and researchers. The authors of the study based their findings on just 11,686 women and then extrapolated the results to all 31,781 women. Study providers did not follow a standard protocol. They used data from just 1 province (Namha) to determine the ectopic pregnancy rate (0.89/1000 woman years of use). Study authors are in the process of doing a separate analysis of ectopic pregnancy rates among all 24 provinces. Yet, it may not represent true rates because of the other inconsistencies in the study. Women may have died from ectopic pregnancy, but the researchers would not know this, since the women lived in rural areas. The medical director of the Association for Voluntary Surgical Contraception objects to the study because quinacrine has not gone through an acceptable and thorough regulatory review process. The study authors said that since the least skilled and experienced clinicians had the highest failure rate, and the most skilled and experienced clinicians had the lowest failure rate (17.2% vs. 5.3%), improved skills and more experience of inserting by clinicians would reduce the failure rate. Later analysis of the data by another group found, however, that failures continued despite the size of the series of women, suggesting that the clinician is consistently not performing the procedure correctly. The group attributes failures to other causes (e.g., in utero blood interfering with the action of quinacrine). Other experts attribute the failures to the technology. Since Vietnam has had an aggressive national population program, and a provider secretly inserted quinacrine in a woman in Vietnam recently during a routine exam, family planners fear that women may be forced to accept the quinacrine method. PMID:12318750

1994-04-01

116

Evolution of Consanguinity in a French Alpine Valley: The Vallouise in the Briançon Region (17th–19th Centuries)  

Microsoft Academic Search

The present study considers the evolution of consanguinity in the Vallouise, a high glacial valley in the French Alps. The genealogical method was used to estimate consanguinity in this Alpine population from the 17th to the 19th centuries. This method was then compared with three other methods used to measure consanguinity. The results indicate that while consanguinity increased through time

Gilles Boëtsch; Michel Prost; Emma Rabino-Massa

2011-01-01

117

A family of dynamic models for large-eddy simulation  

NASA Technical Reports Server (NTRS)

Since its first application, the dynamic procedure has been recognized as an effective means to compute rather than prescribe the unknown coefficients that appear in a subgrid-scale model for Large-Eddy Simulation (LES). The dynamic procedure is usually used to determine the nondimensional coefficient in the Smagorinsky (1963) model. In reality the procedure is quite general and it is not limited to the Smagorinsky model by any theoretical or practical constraints. The purpose of this note is to consider a generalized family of dynamic eddy viscosity models that do not necessarily rely on the local equilibrium assumption built into the Smagorinsky model. By invoking an inertial range assumption, it will be shown that the coefficients in the new models need not be nondimensional. This additional degree of freedom allows the use of models that are scaled on traditionally unknown quantities such as the dissipation rate. In certain cases, the dynamic models with dimensional coefficients are simpler to implement, and allow for a 30% reduction in the number of required filtering operations.

Carati, D.; Jansen, K.; Lund, T.

1995-01-01

118

The frequency and effects of consanguineous marriages in Andhra Pradesh  

Microsoft Academic Search

Summary  1. Investigations were started in 1959 in Andhra Pradesh, India, to find out the frequency of different types of consanguineous\\u000a marriages among the inpatients of King George Hospital in Visakhapatnam, their parents, their children and the parents of\\u000a school children of two schools in Visakhapatnam and one school in Waltair.\\u000a \\u000a 2. Out of 2,177 marriages investigated, 16·6 per cent were

K. R. Dronamraju; P. Meera Khan

1963-01-01

119

Consanguinity and Adverse Pregnancy Outcomes: The North of Jordan Experience  

Microsoft Academic Search

This cross-sectional study was carried out to assess the association between consanguineous marriages and adverse pregnancy\\u000a outcome in the north of Jordan. Women delivered in four major hospitals in the north of Jordan between April 2007 and May\\u000a 2007 were included in the study. Non-Jordanian women and women with multiple pregnancies were excluded. Mothers answered a\\u000a pilot-tested structured questionnaire administered

Basil R. Obeidat; Yousef S. Khader; Zouhair O. Amarin; Mohammad Kassawneh; Mousa Al Omari

2010-01-01

120

Genetic Counseling in Southern Iran: Consanguinity and Reason for Referral  

Microsoft Academic Search

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

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

2008-01-01

121

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

PubMed Central

BACKGROUND—Familial hiatal hernia has only rarely been documented.?AIMS—To describe the pattern of inheritance of familial hiatal hernia within an affected family.?SUBJECTS—Thirty eight members of a family pedigree across five generations.?METHODS—All family members were interviewed and investigated by barium meal for evidence of a hiatal hernia.?RESULTS—Twenty three of 38 family members had radiological evidence of a hiatal hernia. No individual with a hiatal hernia was born to unaffected parents. In one case direct male to male transmission was shown.?CONCLUSIONS—Familial inheritance of hiatal hernia does occur. Evidence of direct male to male transmission points to an autosomal dominant mode of inheritance.???Keywords: familial hiatal hernia; Barrett's oesophagus; autosomal dominant genetics PMID:10517898

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

1999-01-01

122

CALCUL DES INDEX DE SLECTION DANS LE CAS D'INDIVIDUS CONSANGUINS  

E-print Network

CALCUL DES INDEX DE S�LECTION DANS LE CAS D'INDIVIDUS CONSANGUINS ET APPARENT�S QUELCONQUES R'échantillon considéré peuvent être consanguins et apparentés de façon quelconque, et pour un caractère dont la variation phénotypes servent à établir l'index sont issus de parents non apparentés entre eux, et non consanguins

Paris-Sud XI, Université de

123

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

Microsoft Academic Search

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

M L Kulkarni; M Kurian

1990-01-01

124

Fragile X syndrome screening of families with consanguineous and non-consanguineous parents in the Iranian population  

Microsoft Academic Search

Fragile X syndrome is the most common form of inherited mental retardation (MR). It is caused by the expansion of CGG triplet repeats in the fragile X mental retardation 1 (FMR1) gene. In mentally retarded males, the frequency of fragile X syndrome is approximately 2–3 percent, but little is known about its proportion in mentally retarded patients from countries where

Ali Reza Pouya; Seyedeh Sedigheh Abedini; Neda Mansoorian; Farkhondeh Behjati; Nooshin Nikzat; Marzieh Mohseni; Sahar Esmaeeli Nieh; Lia Abbasi Moheb; Hossein Darvish; Gholamreza Bahrami Monajemi; Susan Banihashemi; Kimia Kahrizi; Hans Hilger Ropers; Hossein Najmabadi

2009-01-01

125

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

Microsoft Academic Search

For the present study three castes representing three socioeconomic levels have been selected from Andhra Pradesh, South India. Members of the wealthier castes married consanguineously more frequently than did the members of the lower?ranking castes. The consanguineous unions among all the castes are found to be more fertile than are nonconsanguineous unions. Indeed, fertility increases with degree of relationship of

P. Govinda Reddy

1987-01-01

126

The Frequency of Consanguineous Marriages and Their Effects on Offsprings in Tabriz City  

Microsoft Academic Search

Background: Too much diversity and an ever increasing number of genetic disorders appear as a big challenge in the coming future. One of the main sources of genetic disorders is the consanguineous marriages which are, unfortunately, very common in our society. Objectives: In order to prepare ourselves to accept the challenges regarding congenital mal- formations due to consanguineous marriages, the

Mirza Aghazade A

2010-01-01

127

Consanguinity and Congenital Heart Disease in the Rural Arab Population in Northern Israel  

Microsoft Academic Search

The incidence of congenital heart disease (CHD) was examined in relation to the consanguinity of the parents. The study was performed in five Arab villages in the Western Galilee, Israel, where consanguineous matings are known to be very high. All children up to the age of 7 years were included in this study; there were 1,546 children, 32% were the

David Gev; Nathan Roguin; Emil Freundlich

1986-01-01

128

Genetic structure, consanguineous marriages and economic development: Panel cointegration and panel cointegration neural network analyses  

Microsoft Academic Search

Consanguineous marriages and their effects on human beings in light of biological effects of genetic sicknesses are discussed in many studies. Among many, the likelihood of sicknesses such as phenylketonuria, thalassemia, Landsteiner–Fanconi–Anderson’s syndrome, hemophilia and many neuro system anomalies increase drastically in countries with consanguineous marriage practices resulting in increasing economic costs. In the study, we aimed to analyze the

Melike Bildirici; Özgür Ömer Ersin; Meltem Kökdener

2011-01-01

129

Consanguinity in Spain, 1911–1943: General methodology, behavior of demographic variables, and regional differences  

Microsoft Academic Search

From data on consanguineous marriages in Spain for 1911 to 1943 for the whole country and for four macro regions, the behavior and relationship of consanguinity and demographic variables, such as density, birth rate, death rate, and marriage rate, are demonstrated and discussed. Differences among macro regions for all the variables analyzed and a constant inverse and significant relationship between

G. Zei; A. Moroni

1979-01-01

130

Consanguineous marriage among the parents of hearing impaired students in Baghcheban primary schools  

Microsoft Academic Search

Objective: Genetic studies show that consanguineous marriage can increase the probability of incidence of genetic impairments such as hearing impairments. The target of this study is to identify the prevalence of consanguinity among the parents of hearing impaired students in primary schools. Materials and Methods: We selected all of deaf students of Tehran (614 students). Their mothers answered to questionnaires.

Mansoureh Nikbakht; Ahmadreza Nazeri; Zohreh Amiri

131

Frontotemporal dementia parkinsonism: Clinical findings in a large Iranian family.  

PubMed

Frontotemporal dementia (FTD) is a group of neurodegenerative disorders characterized by atrophy of the frontal and temporal lobes. Clinical features suggestive of FTD include pre-senile onset before the age of 65, behavioral changes, social and interpersonal disinhibition, fluent and nonfluent aphasia, and loss of insight. FTD and parkinsonism linked to chromosome 17 (FTDP-17) was defined during the International Consensus Conference in Ann Arbor, Michigan in 1996. FTDP-17 is an autosomally dominant inherited condition. Most genotypic alterations do not correlate with clinical phenotypes. However, mutations affecting exon 10 splicing are associated with parkinsonism. In the present study, a male case with FTDP who presented with insidious onset of speech difficulty at a young age that was associated with signs of parkinsonism and a positive family history of FTD with MAPT gene mutation at exon 13 has been reported. PMID:25789263

Basiri, Keivan; Ansari, Behnaz; Meamar, Rokhsareh

2015-01-01

132

Frontotemporal dementia parkinsonism: Clinical findings in a large Iranian family  

PubMed Central

Frontotemporal dementia (FTD) is a group of neurodegenerative disorders characterized by atrophy of the frontal and temporal lobes. Clinical features suggestive of FTD include pre-senile onset before the age of 65, behavioral changes, social and interpersonal disinhibition, fluent and nonfluent aphasia, and loss of insight. FTD and parkinsonism linked to chromosome 17 (FTDP-17) was defined during the International Consensus Conference in Ann Arbor, Michigan in 1996. FTDP-17 is an autosomally dominant inherited condition. Most genotypic alterations do not correlate with clinical phenotypes. However, mutations affecting exon 10 splicing are associated with parkinsonism. In the present study, a male case with FTDP who presented with insidious onset of speech difficulty at a young age that was associated with signs of parkinsonism and a positive family history of FTD with MAPT gene mutation at exon 13 has been reported. PMID:25789263

Basiri, Keivan; Ansari, Behnaz; Meamar, Rokhsareh

2015-01-01

133

Large, Rapidly Evolving Intergenic Spacers in the Mitochondrial DNA of the Salamander Family Ambystomatidae (Amphibia: Caudata)  

E-print Network

Large, Rapidly Evolving Intergenic Spacers in the Mitochondrial DNA of the Salamander Family, in the mitochondrial DNA (mtDNA) of all of the sexual species of the salamander family Ambystomatidae, of a shared 240 variation in mitochondrial genome size. In a study of the relationship between endothermy and mtDNA size

Shaffer, H. Bradley

134

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

PubMed

Primary autosomal recessive microcephaly (MCPH) is a genetically heterogeneous condition characterized by congenital microcephaly and intellectual disability. To date, 10 MCPH loci have been identified and due to the genetic heterogeneity of this condition, molecular testing for MCPH can be complicated. Our methods involved employing a next generation sequencing panel of MCPH-related genes allowing for the evaluation of multiple disease loci simultaneously. Next generation sequencing analysis of a 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

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

2014-04-01

135

Papillon–Lefevre syndrome: Reporting consanguinity as a risk factor  

PubMed Central

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

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

2014-01-01

136

Multistep method to deal with large datasets in asteroid family classification  

NASA Astrophysics Data System (ADS)

A fast increase in the number of asteroids with accurately determined orbits and with known physical properties makes it more and more challenging to perform, maintain, and update a classification of asteroids into families. We have therefore developed a new approach to the family classification by combining the Hierarchical Clustering Method (HCM) [1] to identify the families with an automated method to add members to already known families. This procedure makes use of the maximum available information, in particular, of that contained in the proper elements catalog [2]. The catalog of proper elements and absolute magnitudes used in our study contains 336 319 numbered asteroids with an information content of 16.31 Mb. The WISE catalog of albedos [3] and SDSS catalog of color indexes [4] contain 94 632 and 59 975 entries, respectively, with a total amount of information of 0.93 Mb. Our procedure makes use of the segmentation of the proper elements catalog by semimajor axis, to deal with a manageable number of objects in each zone, and by inclination, to account for lower density of high-inclination objects. By selecting from the catalog a much smaller number of large asteroids, in the first step, we identify a number of core families; to these, in the second step, we attribute the next layer of smaller objects. In the third step, we remove all the family members from the catalog, and reapply the HCM to the rest; this gives both satellite families which extend the core families and new independent families, consisting mainly of small asteroids. These two cases are separated in the fourth step by attribution of another layer of new members and by merging intersecting families. This leads to a classification with 128 families and 87 095 members. The list of members is updated automatically with each update of the proper elements catalog, and this represents the final and repetitive step of the procedure. Changes in the list of families are not automated.

Kneževi?, Z.; Milani, A.; Cellino, A.; Novakovi?, B.; Spoto, F.; Paolicchi, P.

2014-07-01

137

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

Microsoft Academic Search

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

Yi Jiang; Mike W. Peng

2011-01-01

138

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

Microsoft Academic Search

Although the probability of both parents being affected by BRCA1 mutations is not negligible, such families have not been systematically described in the literature. Here we present a large breast-ovarian cancer family, where 3 sisters and 1 half-sister inherited maternal BRCA1 5382insC mutation while the remaining 2 sisters carried paternal BRCA1 1629delC allele. No BRCA1 homozygous mutations has been detected,

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

2009-01-01

139

The identification and management of hereditary diffuse gastric cancer in a large Jordanian family  

Microsoft Academic Search

The management of families with hereditary diffuse gastric cancer is challenging as screening for cancer in CDH1 mutation carriers is insufficiently sensitive and the commonly recommended option, prophylactic total gastrectomy, is associated\\u000a with certain morbidity and even potential mortality. We describe the particular challenges associated with the diagnosis and\\u000a management of a large Jordanian family with hereditary diffuse gastric cancer.

Henry T. Lynch; Ibrahim Aldoss; Jane F. Lynch

140

Evidence for ASD Recurrence Rates and Reproductive Stoppage From Large UK ASD Research Family Databases.  

PubMed

Following a diagnosis of a developmental disorder such as autism spectrum disorder (ASD) in early childhood, parents may decide to have fewer children than previously planned. The tendency for families to halt reproduction after receiving a diagnosis for one child is known as reproductive stoppage. Stoppage may lead to an underestimate of recurrence risk estimates of parents having more than one child with ASD. Using two large UK ASD family databases, we investigated recurrence rates for ASD and evidence for reproductive stoppage for both ASD and undiagnosed ASD/broader autism phenotype in a subgroup of families. Reproductive stoppage was tested for using the Mann-Whitney U-test to disprove the null hypothesis that affected and nonaffected children were distributed randomly by birth order. Dahlberg's later-sib method was used to estimate recurrence risk and take stoppage into account. Data were available from 299 families (660 children) including 327 with ASD. Ten percent of the complete families had more than one child with an ASD. Using Dahlberg's later-sib method, the recurrence risk for ASD was 24.7% overall and 50.0% in families with two or more older siblings with ASD. Children with ASD were born significantly later in families than those without ASD in all sibship combinations. This study shows strong evidence that ASD is associated with reproductive stoppage. These data have important implications for family planning and genetic counseling. Autism Res 2015, 8: 73-81. © 2014 International Society for Autism Research, Wiley Periodicals, Inc. PMID:25273900

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

2015-02-01

141

Inbreeding Patterns in La Cabrera, Spain: Dispensations, Multiple Consanguinity Analysis, and Isonymy  

Microsoft Academic Search

Marital structure and inbreeding coefficients were analyzed in La Cabrera, an isolated mountain region in northwestern Spain. A total of 5,714 marriages were celebrated from 1880 to 1989 in the 37 parishes of the area. The total frequency of consanguineous marriages (up to the fourth degree) is 23.05%; multiple consanguineous marriages are remarkably common, reaching 5.43% of the total. The

Maria Jose Blanco Villegas; Alessio Boattini; Humildad Rodriguez Otero; Davide Pettener

2004-01-01

142

Consanguinity Mapping of Congenital Heart Disease in a South Indian Population  

Microsoft Academic Search

BackgroundParental 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

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

2010-01-01

143

Friedreich's Ataxia: An Epidemiological Study in Valencia, Spain, Based on Consanguinity Analysis  

Microsoft Academic Search

Epidemiological studies performed directly on the population show a prevalence of Friedreich's ataxia (FA) from 1 to 4.7 cases\\/100,000 inhabitants. An indirect epidemiological approach can be achieved using genetic methods like consanguinity studies to determine the frequency of a mutated gene and the incidence of certain diseases in the population. We obtained consanguinity data of a series of FA patients

J. M. López-Arlandis; J. J. Vilchez; F. Palau; T. Sevilla

1995-01-01

144

The relationship between consanguineous marriage and death in fetus and infants  

PubMed Central

Background: Given the high prevalence of consanguineous marriages in rural and urban areas of Iran, the aim of this study was to identify its role in increasing fetal and infant deaths. Materials ans Methods: This was a cross-sectional study in which 494 mothers with more than one exceptional child (mentally retarded and physically-dynamically disabled) or with normal children were selected based on multi-stage random sampling method. Data was gathered using the features of parents with more than one exceptional child questionnaire. The validity and reliability of this questionnaire was acceptable. Hierarchical log-linear method was used for statistical analysis. Results: Consanguineous marriage significantly increased the number of births of exceptional children. Moreover, there was a significant relation between the history of fetal/infant death and belonging to the group. There was a significant relation between consanguineous marriage and the history of fetal/infant death which means consanguineous marriage increased the prevalence of fetal/infant death in parents with exceptional children rather than in parents with normal children. Conclusions: The rate of fetal/infant death in exceptional births of consanguineous marriages was higher than that of non-consanguineous marriages. PMID:23626609

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

2012-01-01

145

Health problems, complex life, and consanguinity among ethnic minority Muslim women in Nepal.  

PubMed

Background. Marriage between blood relatives is common among Muslim ethnic minority population in Nepal. Albeit, the adverse effects of such a consanguineous marriage on health are controversial. Objective. To determine the prevalence, characteristics and health outcomes related to consanguineous marriage. Design. A cross-sectional survey was carried out using a cluster sampling technique to select the respondents. A total of 400 women aged 15-49 years were interviewed from September 2011 to February 2012. A structured questionnaire was administered through face-to-face meetings. Adjusted odds ratios (AOR) were estimated by a stepwise likelihood ratio method with binary logistic regression. Results. The overall prevalence of consanguinity was 36.7%. The median age at marriage and age at first childbirth was 15 and 18 years, respectively. The association of being in a consanguineous marriage among women whose husband's education level were secondary or higher was 3.35 (95% CI 1.56, 7.12) times greater than among those whose husbands were unable to read and write. Woman who have consanguineous marriage were less likely to have (AOR 0.46, 95% CI 0.26, 0.82) used contraceptive than those who have non-consanguineous marriage. Women who have consanguineous marriage were more (AOR 1.80; 95% CI 0.90, 3.61) likely to have birth defect in their children than those who have non-consanguineous marriage. The association of having a history of death after live birth among women who experienced emotional violence was 2.60 (95% CI 1.36, 5.00) and physical violence 2.15 (95% CI 1.16, 3.93) times greater than among those who did not experience violence. Conclusions. Several factors like husband's education and dowry practices are associated with consanguineous marriage. Further, these factors including consanguineous marriage and marital violence are also accountable for negative health consequences. Thus, multicomponent interventions are needed in order to improve the health condition of Nepalese Muslim community in rural area. PMID:25397364

Bhatta, Dharma Nand; Haque, Anwarul

2014-11-14

146

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

PubMed Central

Background Most genes in Arabidopsis thaliana are members of gene families. How do the members of gene families arise, and how are gene family copy numbers maintained? Some gene families may evolve primarily through tandem duplication and high rates of birth and death in clusters, and others through infrequent polyploidy or large-scale segmental duplications and subsequent losses. Results Our approach to understanding the mechanisms of gene family evolution was to construct phylogenies for 50 large gene families in Arabidopsis thaliana, identify large internal segmental duplications in Arabidopsis, map gene duplications onto the segmental duplications, and use this information to identify which nodes in each phylogeny arose due to segmental or tandem duplication. Examples of six gene families exemplifying characteristic modes are described. Distributions of gene family sizes and patterns of duplication by genomic distance are also described in order to characterize patterns of local duplication and copy number for large gene families. Both gene family size and duplication by distance closely follow power-law distributions. Conclusions Combining information about genomic segmental duplications, gene family phylogenies, and gene positions provides a method to evaluate contributions of tandem duplication and segmental genome duplication in the generation and maintenance of gene families. These differences appear to correspond meaningfully to differences in functional roles of the members of the gene families. PMID:15171794

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

2004-01-01

147

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

SciTech Connect

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

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

1994-09-01

148

Influence of educational levels of the spouses on consanguinity among three endogamous groups of Andhra Pradesh, South India  

Microsoft Academic Search

The highest values of consanguinity was found among “Kamma” (45.0%), “Ediga” (47.5%) and “Mala” (55.7%) who occupy different\\u000a strata of Indian caste hierarchy. In the way of searchout the factors influencing consanguineous marriages, the present paper\\u000a finda the negative relationship between educational levels of the spouses and consanguinity. The educational levels of men\\u000a has significant effect on the frequency of

A. Chandra Sekar

1995-01-01

149

A large multigene family expressed during the erythrocytic schizogony of Plasmodium falciparum.  

PubMed

We report the identification of a large multigene family of Plasmodium falciparum using a clone isolated with a polyclonal antiserum raised to a Babesia divergens merozoite protein. The recombinant antigen reacted with human sera collected from individuals exposed to malaria. The deduced protein sequence contains a motif homologous to the consensus sequence of merozoite rhoptry proteins encoded by multigene families in several Babesia species. Antibodies raised to the recombinant protein reacted with a 60-kDa merozoite protein both on B. divergens and on P. falciparum immunoblots. The insert hybridized to a large number of fragments on P. falciparum Southern blots and to most chromosomes of the parasite. Specifically, approx. 3-kb RNAs were detected in 4-16-nucleus schizonts. Ten distinct cDNAs were isolated that differed in the size, position and number of restriction sites in the region homologous to the original genomic clone. With about 140 copies per haploid genome, this is the first large multigene family described in malaria parasites. The existence of a multigene family encoding proteins present in the invasive stage of malaria parasites suggests an important role in invasion and denotes a significant potential for generating diversity. PMID:7739668

Carcy, B; Bonnefoy, S; Guillotte, M; Le Scanf, C; Grellier, P; Schrevel, J; Fandeur, T; Mercereau-Puijalon, O

1994-12-01

150

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

PubMed Central

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

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

2014-01-01

151

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

SciTech Connect

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

Edwards, M.J.; Roberts, J.; Partington, M.W. [Newcastle and Northern New South Wales Genetics Service (Australia); Colley, P.W. [John Hunter Hospital, Newcastle (Australia); Hollway, G.E.; Kozman, H.M.; Mulley, J.C. [Adelaide Children`s Hospital, North Adelaide (Australia)

1994-10-15

152

An analysis of consanguinity and social structure within the UK Asian population using microsatellite data.  

PubMed

We analysed microsatellite genotypes sampled from the Pakistani and Indian communities in Nottingham, UK, to investigate the genetic consequences of substructuring mediated by traditional marriage customs. The application of a recently developed likelihood approach identified significant levels of population substructure within the Pakistani community as a whole, as well as within the finer divisions of castes and biradheri. In addition, high levels of cryptic or unacknowledged consanguinity were detected within subgroups of this community, including biradheri. The Indian sample showed no significant evidence of either substructure or consanguinity. We demonstrate that estimates of disease gene frequencies can be inaccurate unless they are made jointly with estimates of population substructure and consanguinity ((theta congruent to FST) and C). The magnitude of these estimates also highlights the importance of accounting for the finer scale of social structuring when making decisions regarding the risk of recessive disorders in offspring. PMID:14641240

Overall, A D J; Ahmad, M; Thomas, M G; Nichols, R A

2003-11-01

153

The advantages of dense marker sets for linkage analysis with very large families.  

PubMed

Dense sets of hundreds of thousands of markers have been developed for genome-wide association studies. These marker sets are also beneficial for linkage analysis of large, deep pedigrees containing distantly related cases. It is impossible to analyse jointly all genotypes in large pedigrees using the Lander-Green Algorithm, however, as marker density increases it becomes less crucial to analyse all individuals' genotypes simultaneously. In this report, an approximate multipoint non-parametric technique is described, where large pedigrees are split into many small pedigrees, each containing just two cases. This technique is demonstrated, using phased data from the International Hapmap Project to simulate sets of 10,000, 50,000 and 250,000 markers, showing that it becomes increasingly accurate as more markers are genotyped. This method allows routine linkage analysis of large families with dense marker sets and represents a more easily applied alternative to Monte Carlo Markov Chain methods. PMID:17252250

Thomson, Russell; Quinn, Stephen; McKay, James; Silver, Jeremy; Bahlo, Melanie; FitzGerald, Liesel; Foote, Simon; Dickinson, Jo; Stankovich, Jim

2007-05-01

154

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

Microsoft Academic Search

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

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

2011-01-01

155

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

SciTech Connect

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

Roussear, M.; Lopes-Cendes, I. [Montreal General Hospital, Quebec (Canada); Berkovic, S.F. [Austin Hospital, Melbourne (Australia)] [and others

1994-09-01

156

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

PubMed

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. PMID:25524067

Bhasin, Prerna; Kapoor, Satwanti

2015-04-01

157

Consanguinity related prenatal and postnatal mortality of the populations of seven Pakistani Punjab cities  

Microsoft Academic Search

A retrospective study was conducted on prenatal and postnatal mortality among the populations of seven cities in the Pakistani province of Punjab. Consanguineous marriages were strongly favoured and the coefficients of inbreeding (F) for the present generation in each locality ranged from 0.0236 to 0.0286. There was a highly significant relationship between the degree of inbreeding and mortality, with most

S A Shami; L H Schmitt; A H Bittles

1989-01-01

158

Consanguineous Marriages and Their Effects on Common Adult Diseases: Studies from an Endogamous Population  

Microsoft Academic Search

Objectives: The aim of the study was to determine the extent and nature of consanguinity in the Qatari population and its effects on common adult diseases. Subjects and Methods: The study was conducted in urban and semi-urban areas of Qatar between October 2004 and May 2005. The total sample of 1,050 married Qatari females 15 years of age and over

Abdulbari Bener; Rafat Hussain; Ahmad S. Teebi

2007-01-01

159

Social Structure and Consanguinity in a French Mountain Population (1550–1849)  

Microsoft Academic Search

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

Emma Rabino-Massa; Michel Prost; Gilles Boetsch

2005-01-01

160

Consanguinity Associated with Child and Adult Mortality in 24 Asian and African Countries, an Ecological Study  

Microsoft Academic Search

Background: Although numerous studies have found deleterious effects of inbreeding on childhood and pre-reproductive mortality, one question remains inadequately addressed: Dose inbreeding lead to increased childhood mortality rates in countries with high level of consanguinity? Methods: To evaluate the public health impact of inbreeding on offspring mortality, the association between mean of inbreeding coefficient (?) and sex specific child and

M Saadat

2007-01-01

161

Concepts of Random Mating and the Frequency of Consanguineous Marriages: Discussion  

Microsoft Academic Search

Formulae due to Dahlberg for computing the numbers of consanguineous matings to be expected under random mating fail in the case of overlapping generations. The concept of random mating can be extended to cover overlapping generations by making the chance of mating between a male and female depend on the interval between their dates of birth. This concept of random

M. Fraccaro; J. Sutter; C. A. B. Smith

1963-01-01

162

Genetic Benefits of Consanguinity Through Selection of Genotypes Protective Against Malaria  

Microsoft Academic Search

Consanguineous marriages are usually socially driven and can be genetically harmful. The detrimental effects of inbreeding are the consequence of homozygosity of harmful genes. On the other hand, beneficial effects of inbreeding, theoretically, could be expected in those who are homozygous for protective recessive and codominant genes. Here, we argue that the most common monogenetic conditions in humans, namely, ?-thalassemia,

Srdjan. Denic; Michael Gary. Nicholls

2007-01-01

163

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

Microsoft Academic Search

41 breast cancer or breast-ovarian cancer families, including 12 families with at least one affected first-degree male relative, were screened for mutations in the BRCA2 gene. Mutations had not been found in the BRCA1 gene of these families. Chemical cleavage of Mismatch was used to identify nucleotide changes within large PCR products (average size 1.2 kb) that carried strand-specific fluorescent

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

2001-01-01

164

A Novel SIX3 Mutation Segregates With Holoprosencephaly in a Large Family  

PubMed Central

Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work-up of a female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holoprosencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from phenotypically normal adults (non-penetrance) to alobar holoprosencephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation. PMID:19353631

Solomon, Benjamin D.; Lacbawan, Felicitas; Jain, Mahim; Domené, Sabina; Roessler, Erich; Moore, Cynthia; Dobyns, William B.; Muenke, Maximilian

2009-01-01

165

The transforming growth factor-(TGF) family of proteins is a large group of secreted pleiotropic cytokines  

E-print Network

The transforming growth factor- (TGF) family of proteins is a large group of secreted pleiotropic transcriptional programmes. The TGF-family members are critically important in the early development of multiple types that deliver the functional cytokine very difficult. However, recent studies that use genetic

Cai, Long

166

[Endogenous psychoses and consanguinity (among an isolated population)].  

PubMed

++Clinico-genealogical and structural-dynamic analyses were made of endogenous psychoses, paranoid in structure under conditions of their accumulation in an isolated population. Study of 3 generations (forefathers, parents, sibs) in 55 families has demonstrated a high level of psychic morbidity among them: schizophrenia (58.1%), epilepsy (24.3%), oligophrenia (8.3%). The combination of schizophrenia and epilepsy was established in 6.3% of cases. It is assumed that the familial forms of psychoses in isolates are inherited by the polygenous autosomal and recessive type. PMID:1965371

Mel'chenko, N I

1990-01-01

167

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

PubMed Central

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

Galindo, K; Smith, D P

2001-01-01

168

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

PubMed Central

Background The application and nutritional value of vegetable oil is highly dependent on its fatty acid composition, especially the relative proportion of its two major fatty acids, i.e oleic acid and linoleic acid. Microsomal oleoyl phosphatidylcholine desaturase encoded by FAD2 gene is known to introduce a double bond at the ?12 position of an oleic acid on phosphatidylcholine and convert it to linoleic acid. The known plant FAD2 enzymes are encoded by small gene families consisting of 1-4 members. In addition to the classic oleate ?12-desaturation activity, functional variants of FAD2 that are capable of undertaking additional or alternative acyl modifications have also been reported in a limited number of plant species. In this study, our objective was to identify FAD2 genes from safflower and analyse their differential expression profile and potentially diversified functionality. Results We report here the characterization and functional expression of an exceptionally large FAD2 gene family from safflower, and the temporal and spatial expression profiles of these genes as revealed through Real-Time quantitative PCR. The diversified functionalities of some of the safflower FAD2 gene family members were demonstrated by ectopic expression in yeast and transient expression in Nicotiana benthamiana leaves. CtFAD2-1 and CtFAD2-10 were demonstrated to be oleate desaturases specifically expressed in developing seeds and flower head, respectively, while CtFAD2-2 appears to have relatively low oleate desaturation activity throughout the plant. CtFAD2-5 and CtFAD2-8 are specifically expressed in root tissues, while CtFAD2-3, 4, 6, 7 are mostly expressed in the cotyledons and hypocotyls in young safflower seedlings. CtFAD2-9 was found to encode a novel desaturase operating on C16:1 substrate. CtFAD2-11 is a tri-functional enzyme able to introduce a carbon double bond in either cis or trans configuration, or a carbon triple (acetylenic) bond at the ?12 position. Conclusions In this study, we isolated an unusually large FAD2 gene family with 11 members from safflower. The seed expressed FAD2 oleate ?12 desaturase genes identified in this study will provide candidate targets to manipulate the oleic acid level in safflower seed oil. Further, the divergent FAD2 enzymes with novel functionality could be used to produce rare fatty acids, such as crepenynic acid, in genetically engineered crop plants that are precursors for economically important phytoalexins and oleochemical products. PMID:23289946

2013-01-01

169

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

PubMed Central

Background. Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years’ detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon. Methods. Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents’ consanguinity were recorded when feasible. Results. The mean age at renal biopsy was 36.76 ± 20 years (range 1–84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001). Conclusions. Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important implications for formulating renal health policies and designing research studies in this population. PMID:20525974

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

2010-01-01

170

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

PubMed Central

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

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

2014-01-01

171

Segregation of FRAXE in a large family: Clinical, psychometric, cytogenetic, and molecular data  

SciTech Connect

During an ongoing study on X-linked mental retardation, we ascertained a large family in which mild mental retardation was cosegregating with a fragile site at Xq27-28. Clinical, psychometric, cytogenetic, and molecular studies were performed. Apart from mild mental retardation, affected males and females did not show a specific clinical phenotype. Psychometric assessment of four representative affected individuals revealed low academic achievements, with verbal and performance IQs of 61-75 and 70-82, respectively. Cytogenetically the fragile site was always present in affected males and was not always present in affected females. With FISH the fragile site was located within the FRAXE region. The expanded GCC repeat of FRAXE was seen in affected males and females either as a discrete band or as a broad smear. No expansion was seen in unaffected males, whereas three unaffected females did have an enlarged GCC repeat. Maternal transmission of FRAXE may lead to expansion or contraction of the GCC repeat length, whereas in all cases of paternal transmission contraction was seen. In striking contrast to the situation in fragile X syndrome, affected males may have affected daughters. In addition, there appears to be no premutation of the FRAXE GCC repeat, since in the family studied here all males lacking the normal allele were found to be affected. 41 refs., 4 figs., 5 tabs.

Hamel, B.C.J.; Smits, A.P.T.; Smeets, F.C.M.; Schoute, F.; Assman-Hulsmans, C.F.C.H. [Univ. Hospital, Nijmegen (Netherlands); Graaff, E. de; Eussen, B.H.J.; Oostra, B.A. [Erasmus Univ., Rotterdam (Netherlands); Knight, S.J.L. [John Radcliffe Hospital, Headington, Oxford (Canada)

1994-11-01

172

The fragile X syndrome in a large family. II. Psychological investigations.  

PubMed Central

Intelligence levels and intelligence profiles were investigated in 52 members of a large family with the fragile X syndrome. The mental abilities were evaluated by the three Wechsler intelligence tests (WAIS, WISC-R, and WPPSI). Chromosomal and psychological data were then compared. In 22 non-retarded fra(X) negative family members, a mean IQ of 102 was found (males 97, females 106). Eleven non-retarded carrier females had IQs between 70 and 110 (mean 86.8), which is 20 points below the mean of normal women (alpha = 0.01). One non-retarded male with 6% fra(X) positive cells had an IQ of 98. His intelligence profile closely resembled the profile in the non-retarded female carriers. The highest IQ in the group of retarded males was 31. The mentally retarded females scored IQs between 26 and 41. In male and female patients verbal intelligence substantially exceeded performance abilities. There was a considerable gap between the highest IQ in the group of retarded females and the lowest IQ in the group of non-retarded carriers (41 and 71 respectively) and a considerable overlap was found between the IQ levels of the non-retarded carriers and normal women. PMID:3806640

Veenema, H; Veenema, T; Geraedts, J P

1987-01-01

173

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

ERIC Educational Resources Information Center

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

Online Submission, 2007

2007-01-01

174

Institutional protocol to manage consanguinity detected by genetic testing in pregnancy in a minor.  

PubMed

Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing. PMID:25687148

Chen, Laura P; Beck, Anita E; Tsuchiya, Karen D; Chow, Penny M; Mirzaa, Ghayda M; Wiester, Rebecca T; Feldman, Kenneth W

2015-03-01

175

Consanguinity and the age of menopause in the United Arab Emirates  

Microsoft Academic Search

Objective: The study examined the association between some biosocial factors, consanguinity and age at natural menopause in the United Arab Emirates (UAE). Method: A cross-sectional population-based study using a multi-stage sampling design and face-to-face interview. Results: In a sample of 800 UAE females aged 40 years and above, there were 742 (85.8%) respondents. The median age of natural menopause was

A Bener; D. E Rizk; M Ezimokhai; M Hassan; R Micallef; M Sawaya

1998-01-01

176

Socioeconomic, Demographic, and Geographic Variables Affecting the Diverse Degrees of Consanguineous Marriages in Spain  

Microsoft Academic Search

In a population the inbreeding coefficient ? is determined by the relative incidence of the various degrees of consanguineous marriages— uncle–niece or aunt–nephew (C12), first cousin (C22), first cousin once re- moved (C23), second cousin (C33)—which may be related to temporal, geographic, demographic, and economic factors. Using published informa- tion from Spain corresponding to urban and rural areas, in this

V. Fuster; S. E. Colantonio

2011-01-01

177

Consanguinity and Associated Socio-Demographic Factors in the United Arab Emirates  

Microsoft Academic Search

The aim of this study was to explore the association between socio-demographic factors and consanguineous marriages in the United Arab Emirates (UAE). This was a cross-sectional population-based study conducted in the cities of Al Ain and Dubai between October 1994 and March 1995. A multi-stage sampling design was used and a representative total sample of 2,200 UAE females aged 15

A. Bener; Y. M. Abdulrazzaq; L. I. Al-Gazali; R. Micallef; A. I. Al-Khayat; T. Gaber

1996-01-01

178

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

PubMed

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 (?) 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 (?) 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?consanguineous couples. PMID:25644872

Bagheri, Mansooreh; Farvardin, Majid; Saadat, Mostafa

2015-04-01

179

Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families  

Microsoft Academic Search

BACKGROUND: BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and\\/or ovarian cancer families. METHODS: Altogether 61 index patients

Katri Pylkäs; Hannele Erkko; Jenni Nikkilä; Szilvia Sólyom; Robert Winqvist

2008-01-01

180

Moxidectin and the avermectins: Consanguinity but not identity  

PubMed Central

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

Prichard, Roger; Ménez, Cécile; Lespine, Anne

2012-01-01

181

Moxidectin and the avermectins: Consanguinity but not identity.  

PubMed

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

Prichard, Roger; Ménez, Cécile; Lespine, Anne

2012-12-01

182

Emergence of Switch-Like Behavior in a Large Family of Simple Biochemical Networks  

PubMed Central

Bistability plays a central role in the gene regulatory networks (GRNs) controlling many essential biological functions, including cellular differentiation and cell cycle control. However, establishing the network topologies that can exhibit bistability remains a challenge, in part due to the exceedingly large variety of GRNs that exist for even a small number of components. We begin to address this problem by employing chemical reaction network theory in a comprehensive in silico survey to determine the capacity for bistability of more than 40,000 simple networks that can be formed by two transcription factor-coding genes and their associated proteins (assuming only the most elementary biochemical processes). We find that there exist reaction rate constants leading to bistability in ?90% of these GRN models, including several circuits that do not contain any of the TF cooperativity commonly associated with bistable systems, and the majority of which could only be identified as bistable through an original subnetwork-based analysis. A topological sorting of the two-gene family of networks based on the presence or absence of biochemical reactions reveals eleven minimal bistable networks (i.e., bistable networks that do not contain within them a smaller bistable subnetwork). The large number of previously unknown bistable network topologies suggests that the capacity for switch-like behavior in GRNs arises with relative ease and is not easily lost through network evolution. To highlight the relevance of the systematic application of CRNT to bistable network identification in real biological systems, we integrated publicly available protein-protein interaction, protein-DNA interaction, and gene expression data from Saccharomyces cerevisiae, and identified several GRNs predicted to behave in a bistable fashion. PMID:21589886

Siegal-Gaskins, Dan; Mejia-Guerra, Maria Katherine; Smith, Gregory D.; Grotewold, Erich

2011-01-01

183

Functional heterogeneity of a large family of human LTR-like promoters and enhancers.  

PubMed Central

The human genome contains a variety of elements similar in structure to retroviruses and retrotransposons. We have shown that the long terminal repeat (LTR) sequences of a large family of human retrovirus-like elements, RTVL-H, are heterogeneous in their ability to regulate the expression of linked genes. Although all of five LTRs tested could promote expression of the chloramphenicol acetyltransferase (CAT) gene, their relative promoter activities as well as range of activities varied widely. Several of the LTRs tested also exhibited bidirectional promoter activity either alone or when activated by an SV40 early enhancer. One LTR, H6, displayed strong promoter activity in human (NTera2D1, 293, Hep2), monkey (COS-1), and mouse (3T3) cells. In fact, the activity of this LTR was similar to that of the SV40 early promoter/enhancer in 293, COS-1, and 3T3 cells. RNA mapping studies have localized the transcription start site to the expected location in the H6 LTR. RTVL-H LTRs were also shown to contain sequences which could increase transcription from the human beta-globin promoter and be influenced by SV40 enhancer sequences. As the human genome contains several hundred related RTVL-H sequences and a similar number of solitary LTRs, these findings raise the possibility that RTVL-H LTRs could have diverse effects on the expression of adjacent cellular genes. Images PMID:1690875

Feuchter, A; Mager, D

1990-01-01

184

Large, rapidly evolving intergenic spacers in the mitochondrial DNA of the salamander family Ambystomatidae (Amphibia: Caudata).  

PubMed

We report the presence, in the mitochondrial DNA (mtDNA) of all of the sexual species of the salamander family Ambystomatidae, of a shared 240-bp intergenic spacer between tRNAThr and tRNAPro. We place the intergenic spacer in context by presenting the sequence of 1,746 bp of mtDNA from Ambystoma tigrinum tigrinum, describe the nucleotide composition of the intergenic spacer in all of the species of Ambystomatidae, and compare it to other coding and noncoding regions of Ambystoma and several other vertebrate mtDNAs. The nucleotide substitution rate of the intergenic spacer is approximately three times faster than the substitution rate of the control region, as shown by comparisons among six Ambystoma macrodactylum sequences and eight members of the Ambystoma tigrinum complex. We also found additional inserts within the intergenic spacers of five species that varied from 87-444 bp in length. The presence of the intergenic spacer in all sexual species of Ambystomatidae suggests that it arose at least 20 MYA and has been a stable component of the ambystomatid mtDNA ever since. As such, it represents one of the few examples of a large and persistent intergenic spacer in the mtDNA of any vertebrate clade. PMID:9364774

McKnight, M L; Shaffer, H B

1997-11-01

185

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

PubMed Central

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

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

2013-01-01

186

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

Microsoft Academic Search

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

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

2007-01-01

187

Family Dinner and Disordered Eating Behaviors in a Large Cohort of Adolescents  

Microsoft Academic Search

We aimed to examine longitudinal associations between family dinner and disordered eating behaviors among adolescents. We studied 7535 females and 5913 males, 9 to 14 years of age in 1996. We performed multivariable logistic regression to assess the associations of previous year family dinner with 1-year incidence of each of 3 outcomes: purging, binge eating, and frequent dieting. Compared to

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

2009-01-01

188

Identification of MYOC gene mutation and polymorphism in a large Malay family with juvenile-onset open angle glaucoma  

PubMed Central

Purpose To screen for mutations in the coding region of the myocilin (MYOC) gene in a large Malay family with juvenile-onset open angle glaucoma (JOAG). Methods A total of 122 family members were thoroughly examined and screened for JOAG. Venipuncture was conducted. Genomic DNA was extracted from peripheral blood leukocytes. The presence of a mutation and a polymorphism was ascertained with PCR amplification followed by the direct sequencing technique. Results Thirty-two of the 122 screened family members were identified to have JOAG (11 new cases and 21 known cases). An autosomal dominant inheritance pattern with incomplete penetrance was observed. A C?A substitution at position 1440 in exon 3 that changes asparagine (AAC) to lysine (AAA) was identified in affected family members except two probands (III:5 and IV:6). Six probands were identified as having the Asn480Lys mutation but have not developed the disease yet. An intronic polymorphism IVS2 730 +35 G>A was also identified. There was a significant association between Asn480Lys (p<0.001) and IVS2 730+35G>A (p<0.001) in the affected and unaffected probands in this family. Conclusions The Asn480Lys mutation and the IVS2 730+35 G>A polymorphism increased susceptibility to JOAG in this large Malay pedigree. Identifying the MYOC mutations and polymorphisms is important for providing presymptomatic molecular diagnosis. PMID:24883016

Mimiwati, Z; Nurliza, K; Marini, M; Liza-Sharmini, AT

2014-01-01

189

Incidence of classic PKU in Italy estimated from consanguineous marriages and from neonatal screening.  

PubMed

As already described for cystic fibrosis and Friedreich ataxia, the incidence of PKU in Italy has been estimated by determining the increase of consanguineous marriages among 178 couples of PKU parents over the frequencies carefully established for the same marriages in the general Italian population for each of the 95 provinces during a 55-year period. The incidence estimated (between 1/15595 and 1/17815 according to two different formulas) is not very different from the incidence derived from screening programs (almost 1/12000). This indicates that the former method can be applied in Italy to the study of the incidence of other autosomal recessive disorders. PMID:6652943

Romeo, G; Menozzi, P; Ferlini, A; Prosperi, L; Cerone, R; Scalisi, S; Romano, C; Antonozzi, I; Riva, E; Piceni Sereni, L

1983-11-01

190

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

PubMed

BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility. In Poland standard BRCA gene test is usually limited to Polish founder BRCA1 mutations: 5382insC, C61G and 4153delA. To date, just a few single large genomic rearrangements (LGRs) of BRCA1 gene have been reported in Poland. Here we report the first comprehensive analysis of large mutations in BRCA1 and BRCA2 genes in this country. We screened LGRs in BRCA1 and BRCA2 genes by multiplex ligation-dependent probe amplification in 200 unrelated patients with strong family history of breast/ovarian cancers and negative for BRCA1 Polish founder mutations. We identified three different LGRs in BRCA1 gene: exons 13-19 deletion, exon 17 deletion and exon 22 deletion. No LGR was detected in BRCA2 genes. Overall, large rearrangements accounted for 3.7 % of all BRCA1 mutation positive families in our population and 1.5 % in high-risk families negative for Polish founder mutation. PMID:24065545

Rudnicka, Helena; Debniak, Tadeusz; Cybulski, Cezary; Huzarski, Tomasz; Gronwald, Jacek; Lubinski, Jan; Gorski, Bohdan

2013-12-01

191

Screening for large genomic rearrangements of the BRIP1 and CHK1 genes in Finnish breast cancer families.  

PubMed

In search for susceptibility genes that could explain an additional portion of familial breast cancer clustering in Finland, we set out to evaluate the presence of large genomic rearrangements in two candidate genes, BRIP1 and CHK1. BRIP1 is a BRCA1 associated protein that is mutated in a fraction of familial breast cancer and Fanconi anemia cases. To date, the role of large BRIP1 deletions in breast cancer susceptibility is not well-characterized. CHK1 is a critical maintainer of cell cycle checkpoints and genomic stability, and is also involved in the BRCA1 and FA protein signalling pathways. Although CHK1 is a very important protein for cell cycle and DNA integrity maintenance control, no mutations in this gene has yet been associated with predisposition to cancer. For the present study, blood DNA from affected index persons of 111 Northern Finnish breast cancer families was assessed for possible constitutional exonic deletions or amplifications in the BRIP1 and CHK1 genes by using the multiplex ligation-dependent probe amplification method. Our results showed that exonic deletions or amplifications affecting the BRIP1 and CHK1 genes seem not to contribute to hereditary breast cancer susceptibility in the Finnish population. To our knowledge, this is the first attempt to determine the existence of large CHK1 deletions in familial breast cancer or in any disease with a hereditary background. PMID:20567916

Solyom, Szilvia; Pylkäs, Katri; Winqvist, Robert

2010-12-01

192

A Consanguinity Related Autosomal Translocation which Leads to Premature Ovarian Failure  

PubMed Central

The premature ovarian failures with underlying chromosomal abnormalities are normally X-linked, although their associations with the autosomal and the Robertsonian translocations are also possible. Here, we are reporting a case of premature ovarian failure which was associated with a translocation between the long arm of chromosome 7 at q11.23 and the short arm of chromosome 5 at p15.3. The proband was a 26-year-old Malay woman who presented with premature ovarian failure, who was referred for cytogenetic testing due to the suspicion of a chromosomal anomaly. Her physical examination revealed that she had no abdominal or pelvic masses and that she had normal secondary sexual characteristics. Her medical history as well, revealed no points for concern. However, a consanguineous relationship existed, as the patient’s paternal grandmother and maternal grandfather were biological cousins. Our present case indicated that region p15.3 of chromosome 5 and region q11.23 of chromosome 7 possibly carried essential genes for the ovarian function and that they postulated a link between the consanguinity and the chromosomal abnormalities. PMID:23543039

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

2013-01-01

193

The Influence of Consanguineous Marriage on Infant and Child Mortality among Palestinians in the West Bank and Gaza, Jordan, Lebanon and Syria  

Microsoft Academic Search

Objectives: The purpose of this paper is to explore the characteristics of mortality differences associated with consanguineous marriage among Palestinians in the Middle East. Methods: The data came from five surveys of Palestinians living in the West Bank and Gaza, Syria, Jordan and Lebanon, conducted during the period 1995–2000. Infant and child mortality was estimated for the offspring of consanguineous

J. Pedersen

2002-01-01

194

Identification of a novel frameshift mutation in the giant muscle filament titin in a large Australian family with dilated cardiomyopathy.  

PubMed

Dilated cardiomyopathy (DCM) is an etiologically heterogeneous cardiac disease characterized by left ventricular dilation and systolic dysfunction. Approximately 25-30% of DCM patients show a family history of mainly autosomal dominant inheritance. We and others have previously demonstrated that mutations in the giant muscle filament titin (TTN) can cause DCM. However, the prevalence of titin mutations in familial DCM is unknown. In this paper, we report a novel heterozygous 1-bp deletion mutation (c.62890delG) in TTN that cosegregates with DCM in a large Australian pedigree (A3). The TTN deletion mutation c.62890delG causes a frameshift, thereby generating a truncated A-band titin due to a premature stop codon (p.E20963KfsX10) and the addition of ten novel amino acid residues. The clinical phenotype of DCM in kindred A3 demonstrates incomplete penetrance and variable expressivity. Finally, protein analysis of a skeletal muscle biopsy sample from an affected member did not reveal the predicted truncated titin isoform although the aberrant mRNA was present, suggesting posttranslational modification and degradation of the truncated protein. The identification of a novel disease-causing mutation in the giant titin gene in a third large family with DCM indicates that mutations in titin may account for a significant portion of the genetic etiology in familial DCM. PMID:16733766

Gerull, Brenda; Atherton, John; Geupel, Anke; Sasse-Klaassen, Sabine; Heuser, Arnd; Frenneaux, Michael; McNabb, Mark; Granzier, Henk; Labeit, Siegfried; Thierfelder, Ludwig

2006-06-01

195

Whole Exome Sequencing Reveals Genetic Predisposition in a Large Family with Retinitis Pigmentosa  

PubMed Central

Next-generation sequencing has become more widely used to reveal genetic defect in monogenic disorders. Retinitis pigmentosa (RP), the leading cause of hereditary blindness worldwide, has been attributed to more than 67 disease-causing genes. Due to the extreme genetic heterogeneity, using general molecular screening alone is inadequate for identifying genetic predispositions in susceptible individuals. In order to identify underlying mutation rapidly, we utilized next-generation sequencing in a four-generation Chinese family with RP. Two affected patients and an unaffected sibling were subjected to whole exome sequencing. Through bioinformatics analysis and direct sequencing confirmation, we identified p.R135W transition in the rhodopsin gene. The mutation was subsequently confirmed to cosegregate with the disease in the family. In this study, our results suggest that whole exome sequencing is a robust method in diagnosing familial hereditary disease. PMID:25101269

Wu, Juan; Chen, Lijia; Tam, Oi Sin; Huang, Xiu-Feng; Pang, Chi-Pui; Jin, Zi-Bing

2014-01-01

196

On family-based genome-wide association studies with large pedigrees: observations and recommendations  

PubMed Central

Family based association studies are employed less often than case-control designs in the search for disease-predisposing genes. The optimal statistical genetic approach for complex pedigrees is unclear when evaluating both common and rare variants. We examined the empirical power and type I error rates of 2 common approaches, the measured genotype approach and family-based association testing, through simulations from a set of multigenerational pedigrees. Overall, these results suggest that much larger sample sizes will be required for family-based studies and that power was better using MGA compared to FBAT. Taking into account computational time and potential bias, a 2-step strategy is recommended with FBAT followed by MGA. PMID:25519377

2014-01-01

197

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

SciTech Connect

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

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

1994-09-01

198

Combining family- and population-based imputation data for association analysis of rare and common variants in large pedigrees.  

PubMed

In the last two decades, complex traits have become the main focus of genetic studies. The hypothesis that both rare and common variants are associated with complex traits is increasingly being discussed. Family-based association studies using relatively large pedigrees are suitable for both rare and common variant identification. Because of the high cost of sequencing technologies, imputation methods are important for increasing the amount of information at low cost. A recent family-based imputation method, Genotype Imputation Given Inheritance (GIGI), is able to handle large pedigrees and accurately impute rare variants, but does less well for common variants where population-based methods perform better. Here, we propose a flexible approach to combine imputation data from both family- and population-based methods. We also extend the Sequence Kernel Association Test for Rare and Common variants (SKAT-RC), originally proposed for data from unrelated subjects, to family data in order to make use of such imputed data. We call this extension "famSKAT-RC." We compare the performance of famSKAT-RC and several other existing burden and kernel association tests. In simulated pedigree sequence data, our results show an increase of imputation accuracy from use of our combining approach. Also, they show an increase of power of the association tests with this approach over the use of either family- or population-based imputation methods alone, in the context of rare and common variants. Moreover, our results show better performance of famSKAT-RC compared to the other considered tests, in most scenarios investigated here. PMID:25132070

Saad, Mohamad; Wijsman, Ellen M

2014-11-01

199

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

PubMed Central

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

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

2013-01-01

200

Consanguineous Marriage in an Urban Area of Saudi Arabia: Rates and Adverse Health Effects on the Offspring  

Microsoft Academic Search

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 coutry because it is in the heart of this industrial region. Five

Abdulkareem A. Al-Abdulkareem; Seifeddin G. Ballal

1998-01-01

201

A Novel PRPF31 Mutation in a Large Chinese Family with Autosomal Dominant Retinitis Pigmentosa and Macular Degeneration  

PubMed Central

Purpose This study was intended to identify the disease causing genes in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration. Methods A genome scan analysis was conducted in this family for disease gene preliminary mapping. Snapshot analysis of selected SNPs for two-point LOD score analysis for candidate gene filter. Candidate gene PRPF31 whole exons' sequencing was executed to identify mutations. Results A novel nonsense mutation caused by an insertion was found in PRPF31 gene. All the 19 RP patients in 1085 family are carrying this heterozygous nonsense mutation. The nonsense mutation is in PRPF31 gene exon9 at chr19:54629961-54629961, inserting nucleotide “A” that generates the coding protein frame shift from p.307 and early termination at p.322 in the snoRNA binding domain (NOP domain). Conclusion This report is the first to associate PRPF31 gene's nonsense mutation and adRP and JMD. Our findings revealed that PRPF31 can lead to different clinical phenotypes in the same family, resulting either in adRP or syndrome of adRP and JMD. We believe our identification of the novel “A” insertion mutation in exon9 at chr19:54629961-54629961 in PRPF31 can provide further genetic evidence for clinical test for adRP and JMD. PMID:24244300

Zheng, Hong; Liu, Xiaoqi; Yang, Jiyun; Shi, Yi; Lin, Ying; Gong, Bo; Zhu, Xianjun; Ma, Shi; Qiao, Lifeng; Lin, He; Cheng, Jing; Yang, Zhenglin

2013-01-01

202

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

Microsoft Academic Search

BackgroundGram-negative bacteria have developed a limited repertoire of solutions for secreting proteins from the cytoplasmic compartment to the exterior of the cell. Amongst the spectrum of secreted proteins are the intimins and invasins (the Int\\/Inv family; TC# 1.B.54) which are characterized by an N-terminal ?-barrel domain and a C-terminal surface localized passenger domain. Despite the important role played by members

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

2010-01-01

203

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

PubMed

The Osiris gene family, first described in Drosophila melanogaster, is clustered in the genomes of all Drosophila species sequenced to date. In D. melanogaster, it explains the enigmatic phenomenon of the triplo-lethal and haploinsufficient locus Tpl. The synteny of Osiris genes in flies is well conserved, and it is one of the largest syntenic blocks in the Drosophila group. By examining the genome sequences of other insects in a wide range of taxonomic orders, we show here that the gene family is well-conserved and syntenic not only in the diptera but across the holometabolous and hemimetabolous insects. Osiris gene homologs have also been found in the expressed sequence tag sequences of various other insects but are absent from all groups that are not insects, including crustacea and arachnids. It is clear that the gene family evolved by gene duplication and neofunctionalization very soon after the divergence of the insects from other arthropods but before the divergence of the insects from one another and that the sequences and synteny have been maintained by selection ever since. PMID:22384409

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

2012-02-01

204

Power of family-based association designs to detect rare variants in large pedigrees using imputed genotypes.  

PubMed

Recently, the "Common Disease-Multiple Rare Variants" hypothesis has received much attention, especially with current availability of next-generation sequencing. Family-based designs are well suited for discovery of rare variants, with large and carefully selected pedigrees enriching for multiple copies of such variants. However, sequencing a large number of samples is still prohibitive. Here, we evaluate a cost-effective strategy (pseudosequencing) to detect association with rare variants in large pedigrees. This strategy consists of sequencing a small subset of subjects, genotyping the remaining sampled subjects on a set of sparse markers, and imputing the untyped markers in the remaining subjects conditional on the sequenced subjects and pedigree information. We used a recent pedigree imputation method (GIGI), which is able to efficiently handle large pedigrees and accurately impute rare variants. We used burden and kernel association tests, famWS and famSKAT, which both account for family relationships and heterogeneity of allelic effect for famSKAT only. We simulated pedigree sequence data and compared the power of association tests for pseudosequence data, a subset of sequence data used for imputation, and all subjects sequenced. We also compared, within the pseudosequence data, the power of association test using best-guess genotypes and allelic dosages. Our results show that the pseudosequencing strategy considerably improves the power to detect association with rare variants. They also show that the use of allelic dosages results in much higher power than use of best-guess genotypes in these family-based data. Moreover, famSKAT shows greater power than famWS in most of scenarios we considered. PMID:24243664

Saad, Mohamad; Wijsman, Ellen M

2014-01-01

205

Hypokalaemic periodic paralysis due to the CACNA1S R1239H mutation in a large African family.  

PubMed

Hypokalaemic periodic paralysis (HypoKPP) is a skeletal muscle channelopathy caused by mutations in calcium (CACNA1S) and sodium (SCN4A) channel subunits. A small number of causative mutations have been found in European and Asian patients, but not in African patients yet. We have identified a large Beninese family in which HypoKPP segregated over five generations and was caused by the CACNA1S R1239H mutation. We report on the clinical and histopathological spectrum of the disorder in this family. A later age at onset (15.8+/-8.8years), and particular triggering factors due to specific African life conditions seem to be characteristic of our observation. PMID:17418573

Houinato, Dismand; Laleye, Anatole; Adjien, Constant; Adjagba, Marius; Sternberg, Damien; Hilbert, Pascale; Vallat, Jean-Michel; Darboux, Raphaël Barthélémy; Funalot, Benoît; Avode, Dossou Gilbert

2007-05-01

206

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

PubMed Central

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

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

2013-01-01

207

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

PubMed

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

Gu, Xun; Wang, Yufeng; Gu, Jianying

2002-06-01

208

Cbl-family ubiquitin ligases and their recruitment of CIN85 are largely dispensable for epidermal growth factor receptor endocytosis.  

PubMed

Members of the casitas B-lineage lymphoma (Cbl) family (Cbl, Cbl-b and Cbl-c) of ubiquitin ligases serve as negative regulators of receptor tyrosine kinases (RTKs). An essential role of Cbl-family protein-dependent ubiquitination for efficient ligand-induced lysosomal targeting and degradation is now well-accepted. However, a more proximal role of Cbl and Cbl-b as adapters for CIN85-endophilin recruitment to mediate ligand-induced initial internalization of RTKs is supported by some studies but refuted by others. Overexpression and/or incomplete depletion of Cbl proteins in these studies is likely to have contributed to this dichotomy. To address the role of endogenous Cbl and Cbl-b in the internalization step of RTK endocytic traffic, we established Cbl/Cbl-b double-knockout (DKO) mouse embryonic fibroblasts (MEFs) and demonstrated that these cells lack the expression of both Cbl-family members as well as endophilin A, while they express CIN85. We show that ligand-induced ubiquitination of EGFR, as a prototype RTK, was abolished in DKO MEFs, and EGFR degradation was delayed. These traits were reversed by ectopic human Cbl expression. EGFR endocytosis, assessed using the internalization of (125)I-labeled or fluorescent EGF, or of EGFR itself, was largely retained in Cbl/Cbl-b DKO compared to wild type MEFs. EGFR internalization was also largely intact in Cbl/Cbl-b depleted MCF-10A human mammary epithelial cell line. Inducible shRNA-mediated knockdown of CIN85 in wild type or Cbl/Cbl-b DKO MEFs had no impact on EGFR internalization. Our findings, establish that, at physiological expression levels, Cbl, Cbl-b and CIN85 are largely dispensable for EGFR internalization. Our results support the model that Cbl-CIN85-endophilin complex is not required for efficient internalization of EGFR, a prototype RTK. PMID:25449262

Ahmad, Gulzar; Mohapatra, Bhopal C; Schulte, Nancy A; Nadeau, Scott A; Luan, Haitao; Zutshi, Neha; Tom, Eric; Ortega-Cava, Cesar; Tu, Chun; Sanada, Masashi; Ogawa, Seishi; Toews, Myron L; Band, Vimla; Band, Hamid

2014-12-01

209

Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family.  

PubMed

Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous disorder. ARRP could be associated with extraocular manifestations that define specific syndromes such as Usher syndrome (USH) characterized by retinal degeneration and congenital hearing loss (HL). The USH type II (USH2) associates RP and mild-to-moderate HL with preserved vestibular function. At least three genes USH2A, the very large G-protein-coupled receptor, GPR98, and DFNB31 are responsible for USH2 syndrome. Here, we report on the segregation of non-syndromic ARRP and USH2 syndrome in a consanguineous Tunisian family, which was previously used to define USH2B locus. With regard to the co-occurrence of these two different pathologies, clinical and genetic reanalysis of the extended family showed (i) phenotypic heterogeneity within USH2 patients and (ii) excluded linkage to USH2B locus. Indeed, linkage analysis disclosed the cosegregation of the USH2 phenotype with the USH2C locus markers, D5S428 and D5S618, whereas the ARRP perfectly segregates with PDE6B flanking markers D4S3360 and D4S2930. Molecular analysis revealed two new missense mutations, p.Y6044C and p.W807R, occurring in GPR98 and PDE6B genes, respectively. In conclusion, our results show that the USH2B locus at chromosome 3p23-24.2 does not exist, and we therefore withdraw this locus designation. The combination of molecular findings for GPR98 and PDE6B genes enable us to explain the phenotypic heterogeneity and particularly the severe ocular affection first observed in one USH2 patient. This report presents an illustration of how consanguinity could increase familial clustering of multiple hereditary diseases within the same family. PMID:18854872

Hmani-Aifa, Mounira; Benzina, Zeineb; Zulfiqar, Fareeha; Dhouib, Houria; Shahzadi, Amber; Ghorbel, Abdelmonem; Rebaï, Ahmed; Söderkvist, Peter; Riazuddin, Sheikh; Kimberling, William J; Ayadi, Hammadi

2009-04-01

210

Segregation patterns and phenotypes of unbalanced offspring in a large family with (10;18) chromosome translocation.  

PubMed

We describe a large family in whom a balanced 10;18 chromosome translocation is segregating through five generations. Six severely mentally retarded relatives and an abnormal fetus further define the phenotypic expression of dup (18q21----qter). Other segregants detected prenatally included a fetus with deletion 18q21----qter and two fetuses with dup(18pter----q21) owing to tertiary trisomy. One of the latter also had an extra X chromosome; this might be another example of possible nonhomologous pairing in man. PMID:4073123

Bernstein, R; Pinto, M R; Kromberg, J; Wagner, J; Jenkins, T

1985-12-01

211

A family of derivative-free conjugate gradient methods for large-scale nonlinear systems of equations  

NASA Astrophysics Data System (ADS)

In this paper, we propose a family of derivative-free conjugate gradient methods for large-scale nonlinear systems of equations. They come from two modified conjugate gradient methods [W.Y. Cheng, A two term PRP based descent Method, Numer. Funct. Anal. Optim. 28 (2007) 1217-1230; L. Zhang, W.J. Zhou, D.H. Li, A descent modified Polak-Ribiére-Polyak conjugate gradient method and its global convergence, IMA J. Numer. Anal. 26 (2006) 629-640] recently proposed for unconstrained optimization problems. Under appropriate conditions, the global convergence of the proposed method is established. Preliminary numerical results show that the proposed method is promising.

Cheng, Wanyou; Xiao, Yunhai; Hu, Qing-Jie

2009-02-01

212

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

PubMed

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

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

2014-08-01

213

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

PubMed Central

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

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

2014-01-01

214

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

PubMed Central

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

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

2015-01-01

215

Phenotypic Characterization of a Large Family With RP10 Autosomal-Dominant Retinitis Pigmentosa  

PubMed Central

PURPOSE To evaluate the clinical features associated with the RP10 form of autosomal-dominant retinitis pigmentosa in 11 affected members of various ages from one family with a defined IMPDH1 mutation (Asp226Asn). DESIGN Prospective, observational case series. METHODS Visual function assessment included visual acuity, color vision, visual field, dark adaptometry, full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Ophthalmologic examinations, fundus photography, and optical coherence tomographic scans were also performed. Blood samples were obtained to screen for basic immune function. RESULTS Visual acuity was slightly reduced in the teenage years and substantially reduced in association with cystoid macular edema (CME) at all ages. Color defects were observed in three patients (one teen, two adults). Dark-adapted thresholds were elevated. Visual fields were markedly constricted by age 40 (?20 degrees). Rod and cone a-wave and b-wave ffERG responses were small or nondetectable by age 20, with greater rod than cone loss at all ages. The normal to significantly delayed ffERG cone b-wave implicit times in different patients were explained by their mfERG implicit times from the central retina. The amplification factors (log S) and recovery kinetics derived from the full-field rod a-waves were normal. Optical coherence tomography revealed subretinal fluid accumulation in the majority of eyes. Cystoid macular edema was diagnosed in four patients. No unusual immunologic findings were noted. CONCLUSIONS The Asp226Asn mutation is associated with a severe, early-onset form of retinal degeneration in members of this family. PMID:16214101

KOZMA, PETRA; HUGHBANKS-WHEATON, DIANNA K.; LOCKE, KIRSTEN G.; FISH, GARRY E.; GIRE, ANISA I.; SPELLICY, CATHERINE J.; SULLIVAN, LORI S.; BOWNE, SARA J.; DAIGER, STEPHEN P.; BIRCH, DAVID G.

2008-01-01

216

Exome sequencing of 75 individuals from multiply affected coeliac families and large scale resequencing follow up.  

PubMed

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

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

2015-01-01

217

The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma  

PubMed Central

Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16INK4a and p14ARF. Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene. PMID:18612309

Lesueur, F; de Lichy, M; Barrois, M; Durand, G; Bombled, J; Avril, M-F; Chompret, A; Boitier, F; Lenoir, G M; Bressac-de Paillerets, B

2008-01-01

218

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

SciTech Connect

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

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

1996-06-01

219

Analysis of Arabidopsis genome sequence reveals a large new gene family in plants  

Microsoft Academic Search

A detailed analysis of the currently available Arabidopsis thaliana genomic sequence has revealed the presence of a large number of open reading frames with homology to the stigmatic self-incompatibility (S) genes of Papaver rhoeas. The products of these potential genes are all predicted to be relatively small, basic, secreted proteins with similar predicted secondary structures. We have named these potential

J. P. Ride; E. M. Davies; F. C. H. Franklin; D. F. Marshall

1999-01-01

220

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

SciTech Connect

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

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

2005-09-28

221

Familial Mediterranean fever associated with MEFV mutations in a large cohort of Cypriot patients.  

PubMed

Familial Mediterranean fever (FMF) is caused by mutations in the MEFV gene and the spectrum of mutations among Greek-Cypriots with FMF-related symptoms was examined. Sequence analysis for exons 2, 3, 5, and 10 of the MEFV gene was performed in a cohort of 593 patients. A total of 70 patients carried mutations in the homozygote or compound heterozygote state, 128 were identified with one MEFV mutation and 395 had no mutations. Of the 268 identified alleles, p.Val726Ala (27.61%) was the most frequent followed by p.Met694Val (19.40%). The missense mutations p.Arg761His (3.73%) and p.Ala744Ser (2.24%) were identified as the rarest. An interesting finding is the high frequency (18.28%) of the complex p.Phe479Leu-p.Glu167Asp that was identified in 49 of the mutated alleles. The MEFV genotypes did not follow a binomial distribution and proved not to satisfy the HWE (P < 0.001). The high percentage (66.61%) of patients with unidentified mutations could be due to mutations in the rest of the coding or noncoding MEFV gene or due to mutations in other genes that are also causing Hereditary Recurrent Fevers. Results from this work indicate the high incidence of FMF in Cyprus and describe the spectrum of the mutations which occur in the country. PMID:25393764

Neocleous, Vassos; Costi, Constantina; Kyriakou, Christina; Kyriakides, Tassos C; Shammas, Christos; Skordis, Nicos; Toumba, Meropi; Kyriakou, Sophia; Koliou, Maria; Kousparou, Marianna; Onoufriou, Margarita; Hadjipanayis, Adamos; Iasonides, Michalis; Atamyan, Vick N; Pierides, Alkis; Christophidou-Anastasiadou, Violetta; Tanteles, George A; Phylactou, Leonidas A

2015-01-01

222

Significant contribution of large BRCA1 gene rearrangements in 120 French breast and ovarian cancer families  

Microsoft Academic Search

Genetic linkage data have shown that alterations of the BRCA1 gene are responsible for the majority of hereditary breast-ovarian cancers. However, BRCA1 germline mutations are found much less frequently than expected, especially as standard PCR-based mutation detection approaches focus on point and small gene alterations. In order to estimate the contribution of large gene rearrangements to the BRCA1 mutation spectrum,

Sophie Gad; Virginie Caux-Moncoutier; Sabine Pagès-Berhouet; Marion Gauthier-Villars; Isabelle Coupier; Pascal Pujol; Marc Frénay; Brigitte Gilbert; Christine Maugard; Yves-Jean Bignon; Annie Chevrier; Annick Rossi; Jean-Pierre Fricker; Tan Dat Nguyen; Liliane Demange; Alain Aurias; Aaron Bensimon; Dominique Stoppa-Lyonnet

2002-01-01

223

Large gene family expansion and variable selective pressures for cathepsin B in aphids.  

PubMed

Aphids exclusively feed on plant phloem sap that contains much sugar and some nonessential amino acids but is poor in lipids and proteins. Conventionally, it has been believed that aphids substantially have no intestinal digestion of proteins. However, we here report an unexpected finding that cysteine protease genes of the family cathepsin B are massively amplified in the lineage of aphids and that many of the protease genes exhibit gut-specific overexpression. By making use of expressed sequence tag data, sequenced cDNAs, and genomic trace sequences of the pea aphid Acyrthosiphon pisum, we identified a total of 28 cathepsin B-like gene copies in the genome of A. pisum. Phylogenetic analyses of all the cathepsin B genes in aphids revealed that genic expansion has continuously proceeded with basal, intermediary, and recent duplications. Estimation of molecular evolutionary rates indicated that major alterations of the rates often occurred after duplications. For example, a gene copy ("348") was shown to be slow evolving and close to genes of other insects like Drosophila melanogaster, whereas the other gene copies appeared to have evolved faster with higher ratios of nonsynonymous to synonymous substitutions. We identified a number of gene copies (16 in A. pisum) that contained a replacement at the site required for catalytic activity of the protease. Among these, 2 copies were pseudogenes, whereas the remaining copies were structurally intact and possibly acquired new functions. For example, a cluster of such gene copies ("1674") has been subjected to positive selection. Quantitative reverse transcriptase-polymerase chain reaction analyses revealed that the more conserved gene copy ("348") showed a constitutive expression, whereas 5 other forms ("84," "16," "16D," "1874," and "2744") were preferentially expressed in the gut of A. pisum. Putative biological roles of the diversified cathepsin B-like gene copies in aphids are discussed in relation to their nutritional physiology specialized for plant sap feeding lifestyle. PMID:17934209

Rispe, Claude; Kutsukake, Mayako; Doublet, Vincent; Hudaverdian, Sylvie; Legeai, Fabrice; Simon, Jean-Christophe; Tagu, Denis; Fukatsu, Takema

2008-01-01

224

A lethal osteochondrodysplasia with mesomelic brachymelia, round pelvis, and congenital hepatic fibrosis: two siblings born to consanguineous parents  

Microsoft Academic Search

We report a hitherto unknown, lethal osteochondrodysplasia in two Japanese siblings born to consanguineous parents. The skeletal\\u000a abnormalities are characterised by mesomelic brachymelia with bowed forearms, a round pelvis with shortened greater sciatic\\u000a notches, an ossification defect of the pubic bones, and absence of ossification centers in the cervical vertebral bodies.\\u000a The associated visceral anomalies comprised periportal fibrosis and cystic

Gen Nishimura; Masahiro Nakayama; Yoshio Fuke; Noriyuki Suehara

1998-01-01

225

Influence of Consanguinity and Maternal Education on Risk of Stillbirth and Infant Death in Norway, 1967-1993  

Microsoft Academic Search

To analyze the influence of consanguinity and maternal education on stillbirth and infant death for children born in Norway between 1967 and 1993, the authors studied 7,274 children of ethnic Pakistani origin and 1,431,055 children of Norwegian ethnic origin. Of these children, 31.0% of the Pakistani children and 0.1 % of the Norwegian children had parents who were first cousins.

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

226

Local Differences in the Archbishopric of Santiago de Compostela (Galicia, Spain) in Relation to the Consanguinity Structure, 1900–1979  

Microsoft Academic Search

The microgeographic variability of consanguinity in the Archbishopric of Santiago de Compostela (Galicia) between 1900 and 1979 was studied. This Archbishopric covers 106 local councils integrated by 964 parishes, of which 677 (70.23%) were analyzed. Of the 307,094 marriages counted within this period, 15,739 corresponded to weddings between biologically related couples. Within the Archbishopric, eight geographical regions were considered: six

C. Sánchez-Sellero; J. Fariña; R. L. Aínsua; T. A. Valera

2011-01-01

227

Premarital genetic counselling to consanguineous couples: Attitudes, beliefs and decisions among counselled, noncounselled and unrelated couples in Israel  

Microsoft Academic Search

Semi-structured interviews were conducted with 65 Israeli subjects who received genetic counselling while considering marriage to a close relative, 40 subjects married to a close relative who did not receive pre-marital genetic counselling, and 125 controls married to a nonrelative and never having considered marrying a relative. It was found that 72% of the consanguineous couples who received pre-marital genetic

Shoshana Shiloh; Haike Reznik; Mariassa Bat-Miriam-Katznelson; Boleslav Goldman

1995-01-01

228

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

PubMed Central

In communities with high rates of consanguinity and consequently high prevalence of recessive phenotypes, homozygosity mapping with SNP arrays is an effective approach for gene discovery. In 20 Palestinian kindreds with prelingual nonsyndromic hearing loss, we generated homozygosity profiles reflecting linkage to the phenotype. Family sizes ranged from small nuclear families with two affected children, one unaffected sibling, and parents to multigenerational kindreds with 12 affected relatives. By including unaffected parents and siblings and screening 250?K SNP arrays, even small nuclear families yielded informative profiles. In 14 families, we identified the allele responsible for hearing loss by screening a single candidate gene in the longest homozygous region. Novel alleles included missense, nonsense, and splice site mutations of CDH23, MYO7A, MYO15A, OTOF, PJVK, Pendrin/SLC26A4, TECTA, TMHS, and TMPRSS3, and a large genomic deletion of Otoancorin (OTOA). All point mutations were rare in the Palestinian population (zero carriers in 288 unrelated controls); the carrier frequency of the OTOA genomic deletion was 1%. In six families, we identified five genomic regions likely to harbor novel genes for human hearing loss on chromosomes 1p13.3 (DFNB82), 9p23–p21.2/p13.3–q21.13 (DFNB83), 12q14.3–q21.2 (DFNB84; two families), 14q23.1–q31.1, and 17p12–q11.2 (DFNB85). PMID:19888295

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

2010-01-01

229

A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess  

SciTech Connect

A mutation in the HSD11B2 gene has been discovered in a consanguineous Iranian family with three sibs suffering from Apparent Mineralocorticoid Excess (AME). Sequence data demonstrate a C to T transition resulting in an R337C mutation. 9 refs., 2 figs., 3 tabs.

Wilson, R.C.; Harbison, M.D.; Wei, J.Q. [New York Hospital-Cornell Medical Center, NY (United States)] [and others] [New York Hospital-Cornell Medical Center, NY (United States); and others

1995-07-01

230

A Novel ESRRB Deletion Is a Rare Cause of Autosomal Recessive Nonsyndromic Hearing Impairment among Pakistani Families  

PubMed Central

Mutations in the estrogen-related receptor beta (ESRRB) gene is the underlying cause of autosomal recessive nonsyndromic hearing impairment (ARNSHI) due to the DFNB35 locus which maps to 14q24.3. A genome scan of a large consanguineous Pakistani pedigree with ARNSHI established linkage with a maximum multipoint LOD score of 4.2 to the 14q24 region and the region of homozygosity contained the ESRRB gene. Sequencing of the ESRRB gene using DNA samples from hearing-impaired family members uncovered a novel three-nucleotide deletion c.1018_1020delGAG (p.Glu340del). The deletion segregates with hearing impairment in the pedigree and was not observed in 500 control chromosomes. The deletion of glutamic acid residue occurs in the ligand-binding domain of ESRRB protein. It is expected that the deletion affects the ligand-binding activity of the domain in ESRRB, which leads to the ARNSHI. PMID:22567352

Lee, Kwanghyuk; Khan, Saadullah; Ansar, Muhammad; Santos-Cortez, Regie Lyn P.; Ahmad, Wasim; Leal, Suzanne M.

2011-01-01

231

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

PubMed

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

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

2014-05-01

232

Protein-bound molecules: a large family with a bad character.  

PubMed

Many small solutes excreted by the kidney are bound to plasma proteins, chiefly albumin, in the circulation. The combination of protein binding and tubular secretion allows the kidney to reduce the free, unbound concentrations of such solutes to lower levels than could be obtained by tubular secretion alone. Protein-bound solutes accumulate in the plasma when the kidneys fail, and the free, unbound levels of these solutes increase more than their total plasma levels owing to competition for binding sites on plasma proteins. Given the efficiency by which the kidney can clear protein-bound solutes, it is tempting to speculate that some compounds in this class are important uremic toxins. Studies to date have focused largely on two specific protein-bound solutes: indoxyl sulfate and p-cresyl sulfate. The largest body of evidence suggests that both of these compounds contribute to cardiovascular disease, and that indoxyl sulfate contributes to the progression of chronic kidney disease. Other protein-bound solutes have been investigated to a much lesser extent, and could in the future prove to be even more important uremic toxins. PMID:24780467

Sirich, Tammy L; Meyer, Timothy W; Gondouin, Bertrand; Brunet, Philippe; Niwa, Toshimitsu

2014-03-01

233

A large deletion encompassing the entire alpha-like globin gene cluster in a family of northern European extraction.  

PubMed Central

We describe a new deletional form of alpha thalassemia segregating in three generations of a family of northern European origin. A full-term female girl had hypochromic, microcytic anemia since early infancy associated with delayed language development, slow growth and weight gain. Hematologic studies suggested the presence of alpha thalassemia. Gene-blotting studies showed no abnormal alpha-like globin gene fragments; however, studies of inheritance of informative polymorphic restriction fragments using zeta, alpha and 3'-alpha-hypervariable region (3'-HVR) probes showed evidence for an extensive deletion encompassing the entire alpha-like globin gene cluster. The 3' breakpoint of this deletion maps beyond the 3'-HVR, a region implicated as a hot spot for the generation of other large deletional events within the alpha-like cluster. The 5' breakpoint maps at least 10 kilobases (kb) 5' to the zeta-globin gene. The minimum size estimate for this deletion is greater than 47 kilobases. Images PMID:2905048

Fortina, P; Delgrosso, K; Rappaport, E; Poncz, M; Ballas, S K; Schwartz, E; Surrey, S

1988-01-01

234

Targeted High-Throughput Sequencing Identifies Pathogenic Mutations in KCNQ4 in Two Large Chinese Families with Autosomal Dominant Hearing Loss  

PubMed Central

Autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous, among them, KCNQ4 is one of the most frequent disease-causing genes. More than twenty KCNQ4 mutations have been reported, but none of them were detected in Chinese mainland families. In this study, we identified a novel KCNQ4 mutation in a five generation Chinese family with 84 members and a known KCNQ4 mutation in a six generation Chinese family with 66 members. Mutation screening of 30 genes for ADNSHL was performed in the probands from thirty large Chinese families with ADNSHL by targeted region capture and high-throughput sequencing. The candidate variants and the co-segregation of the phenotype were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing in all ascertained family members. Then we identified a novel KCNQ4 mutation p.W275R in exon 5 and a known KCNQ4 mutation p.G285S in exon 6 in two large Chinese ADNSHL families segregating with post-lingual high frequency-involved and progressive sensorineural hearing loss. This is the first report of KCNQ4 mutation in Chinese mainland families. KCNQ4, a member of voltage-gated potassium channel family, is likely to be a common gene in Chinese patients with ADNSHL. The results also support that the combination of targeted enrichment and high-throughput sequencing is a valuable molecular diagnostic tool for autosomal dominant hereditary deafness. PMID:25116015

Gao, Yun; Liu, Qiong; Wang, Dayong; Li, Qian; Lan, Lan; Li, Na; Guan, Jing; Yin, Zifang; Han, Bing; Zhao, Feifan; Zong, Liang; Xiong, Wenping; Yu, Lan; Song, Lijie; Yi, Xin; Yang, Ling; Petit, Christine; Wang, Qiuju

2014-01-01

235

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

SciTech Connect

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

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

2010-08-17

236

Large Deviations for Stationary Probabilities of a Family of Continuous Time Markov Chains via Aubry-Mather Theory  

NASA Astrophysics Data System (ADS)

In the present paper, we consider a family of continuous time symmetric random walks indexed by kin {N} , {X_k(t), t?0} . For each kin {N} the matching random walk take values in the finite set of states ? _k=1/k({Z}/k{Z}) ; notice that ? _k is a subset of {S}^1 , where {S}^1 is the unitary circle. The infinitesimal generator of such chain is denoted by L_k . The stationary probability for such process converges to the uniform distribution on the circle, when k? ?. Here we want to study other natural measures, obtained via a limit on k? ?, that are concentrated on some points of {S}^1 . We will disturb this process by a potential and study for each k the perturbed stationary measures of this new process when k? ?. We disturb the system considering a fixed C^2 potential V: {S}^1 ? {R} and we will denote by V_k the restriction of V to ? _k . Then, we define a non-stochastic semigroup generated by the matrix k L_k + k V_k , where k L_k is the infinifesimal generator of {X_k(t), t? 0} . From the continuous time Perron's Theorem one can normalized such semigroup, and, then we get another stochastic semigroup which generates a continuous time Markov Chain taking values on ? _k . This new chain is called the continuous time Gibbs state associated to the potential k V_k , see (Lopes et al. in J Stat Phys 152:894-933, 2013). The stationary probability vector for such Markov Chain is denoted by ? _{k,V} . We assume that the maximum of V is attained in a unique point x_0 of {S}^1 , and from this will follow that ? _{k,V}? ? _{x_0} . Thus, here, our main goal is to analyze the large deviation principle for the family ? _{k,V} , when k ? ?. The deviation function I^V , which is defined on {S}^1 , will be obtained from a procedure based on fixed points of the Lax-Oleinik operator and Aubry-Mather theory. In order to obtain the associated Lax-Oleinik operator we use the Varadhan's Lemma for the process {X_k(t), t? 0} . For a careful analysis of the problem we present full details of the proof of the Large Deviation Principle, in the Skorohod space, for such family of Markov Chains, when k? ?. Finally, we compute the entropy of the invariant probabilities on the Skorohod space associated to the Markov Chains we analyze.

Lopes, Artur O.; Neumann, Adriana

2015-02-01

237

Familial chondrocalcinosis in the Chiloe Islands, Chile.  

PubMed

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

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

1975-06-01

238

Familial chondrocalcinosis in the Chiloe Islands, Chile.  

PubMed Central

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

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

239

Bernard-Soulier syndrome in two Afrikaner families.  

PubMed

The hereditary autosomal recessive disorder of platelet function known as the Bernard-Soulier syndrome (B-SS) is described in two Afrikaner families. Consanguinity exists in one of the families, which is descended from Trekboer Afrikaners who migrated from Rustenburg, Transvaal, to Angola in 1876 and then to SWA/Namibia in the 1920s. Since both families have French Huguenot ancestors and since there are 7 confirmed and 5 reported cases of B-SS in these two families, founder effect may be operating and causing this rare disorder to occur more frequently in this population group than would otherwise be expected. PMID:4040267

Grové, S S; Kromberg, J G

1985-06-29

240

Chlamydia abortus YhbZ, a truncated Obg family GTPase, associates with the Escherichia coli large ribosomal subunit.  

PubMed

The stringent stress response is vital for bacterial survival under adverse environmental conditions. Obligate intracellular Chlamydia lack key stringent response proteins, but nevertheless can interrupt the cell cycle and enter stasis or persistence upon amino acid starvation. A possible key protein retained is YhbZ, a homologue of the ObgE guanosine triphosphatase (GTPase) superfamily connecting the stringent stress response to ribosome maturation. Curiously, chlamydial YhbZ lacks the ObgE C-terminal domain thought to be essential for binding the large ribosomal subunit. We expressed recombinant Chlamydia abortus YhbZ and showed it to be a functional GTPase, with similar activity to other Obg GTPase family members. As Chlamydia are resistant to genetic manipulation, we performed heterologous expression and gradient centrifugation experiments in Escherichia coli and found that, despite the missing C-terminal domain, C. abortus YhbZ co-fractionates with the E. coli 50S large ribosomal subunit. In addition, overexpression of chlamydial YhbZ in E. coli leads to growth defects and elongation, as reported for other Obg members. YhbZ did not complement an E. coli obgE temperature-sensitive mutant, indicating the C-terminal acidic domain may have an additional role. This data supports a role for YhbZ linking the chlamydial stress response to ribosome function and cellular growth. PMID:21195156

Polkinghorne, Adam; Vaughan, Lloyd

2011-01-01

241

A canonical splice site mutation in GIPC3 causes sensorineural hearing loss in a large Pakistani family.  

PubMed

With homozygosity mapping we have identified two large homozygous regions on chromosome 3q13.11-q13.31 and chromosome 19p13.3-q31.32 in a large Pakistani family suffering from autosomal recessive nonsyndromic hearing impairment (arNSHI). The region on chromosome 19 overlaps with the previously described deafness loci DFNB15, DFNB72 and DFNB95. Mutations in GIPC3 have been shown to underlie the nonsyndromic hearing impairment linked to these loci. Sequence analysis of all exons and exon-intron boundaries of GIPC3 revealed a homozygous canonical splice site mutation, c.226-1G>T, in GIPC3. This is the first mutation described in GIPC3 that affects splicing. The c.226-1G>T mutation is located in the acceptor splice site of intron 1 and is predicted to affect the normal splicing of exon 2. With a minigene assay it was shown to result in the use of an alternative acceptor site in exon 2, resulting in a frameshift and a premature stop codon. This study expands the mutational spectrum of GIPC3 in arNSHI. PMID:25296581

Siddiqi, Saima; Ismail, Muhammad; Oostrik, Jaap; Munawar, Saba; Mansoor, Atika; Kremer, Hannie; Qamar, Raheel; Schraders, Margit

2014-12-01

242

Accuracy of genomic selection models in a large population of open-pollinated families in white spruce.  

PubMed

Genomic selection (GS) is of interest in breeding because of its potential for predicting the genetic value of individuals and increasing genetic gains per unit of time. To date, very few studies have reported empirical results of GS potential in the context of large population sizes and long breeding cycles such as for boreal trees. In this study, we assessed the effectiveness of marker-aided selection in an undomesticated white spruce (Picea glauca (Moench) Voss) population of large effective size using a GS approach. A discovery population of 1694 trees representative of 214 open-pollinated families from 43 natural populations was phenotyped for 12 wood and growth traits and genotyped for 6385 single-nucleotide polymorphisms (SNPs) mined in 2660 gene sequences. GS models were built to predict estimated breeding values using all the available SNPs or SNP subsets of the largest absolute effects, and they were validated using various cross-validation schemes. The accuracy of genomic estimated breeding values (GEBVs) varied from 0.327 to 0.435 when the training and the validation data sets shared half-sibs that were on average 90% of the accuracies achieved through traditionally estimated breeding values. The trend was also the same for validation across sites. As expected, the accuracy of GEBVs obtained after cross-validation with individuals of unknown relatedness was lower with about half of the accuracy achieved when half-sibs were present. We showed that with the marker densities used in the current study, predictions with low to moderate accuracy could be obtained within a large undomesticated population of related individuals, potentially resulting in larger gains per unit of time with GS than with the traditional approach. PMID:24781808

Beaulieu, J; Doerksen, T; Clément, S; MacKay, J; Bousquet, J

2014-10-01

243

Escobar syndrome in three male patients of same family  

PubMed Central

We describe three male individuals from a consanguineous south Indian family affected with the multiple pterygium syndrome (Escobar syndrome). Common clinical features included short stature, multiple pterygium, skeletal anomalies, and normal intelligence. The first report of this condition was made in 1902 from this same place (Pondicherry) and the disease received its present popular name Escobar syndrome in 1982. The genetic defect for this condition was identified in 2006 as mutation in the fetal acetylcholine receptor. PMID:21814339

Amalnath, Deepak S.; Subrahmanyam, D. K. S.; Sridhar, S.; Dutta, T. K.

2011-01-01

244

Atrichia with papular lesions in two Pakistani consanguineous families resulting from mutations in the human hairless gene  

Microsoft Academic Search

Atrichia with papular lesions (APL) is a rare autosomal recessive form of total alopecia, characterized by hair loss soon\\u000a after birth and the development of papular lesions of keratin-filled cysts over extensive areas of the body. Mutations in\\u000a the hairless (hr) gene, a putative single zinc finger transcription factor, have been implicated in the pathogenesis of this\\u000a disorder. In the

Peter John; Muhammad Aslam; Muhammad Arshad Rafiq; Muhammad Amin-ud-din; Sayedul Haque; Wasim Ahmad

2005-01-01

245

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

PubMed Central

Imputation has been widely used in genome-wide association studies (GWAS) to infer genotypes of un-genotyped variants based on the linkage disequilibrium in external reference panels such as the HapMap and 1000 Genomes. However, imputation has only rarely been performed based on family relationships to infer genotypes of un-genotyped individuals. Using 8998 Framingham Heart Study (FHS) participants genotyped with Affymetrix 550K SNPs, we imputed genotypes of same set of SNPs for additional 3121 participants, most of whom were never genotyped due to lack of DNA sample. Prior to imputation, 122 pedigrees were too large to be handled by the imputation software Merlin. Therefore, we developed a novel pedigree splitting algorithm that can maximize the number of genotyped relatives for imputing each un-genotyped individual, while keeping new sub-pedigrees under a pre-specified size. In GWAS of four phenotypes available in FHS (Alzheimer disease, circulating levels of fibrinogen, high-density lipoprotein cholesterol, and uric acid), we compared results using genotyped individuals only with results using both genotyped and imputed individuals. We studied the impact of applying different imputation quality filtering thresholds on the association results and did not found a universal threshold that always resulted in a more significant p-value for previously identified loci. However most of these loci had a lower p-value when we only included imputed genotypes with with ?60% SNP- and ?50% person-specific imputation certainty. In summary, we developed a novel algorithm for splitting large pedigrees for imputation and found a plausible imputation quality filtering threshold based on FHS. Further examination may be required to generalize this threshold to other studies. PMID:23284720

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

2012-01-01

246

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

ERIC Educational Resources Information Center

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

Rambla, Xavier; Valiente, Oscar; Frias, Carla

2011-01-01

247

An Exploratory Analysis of Family Coping Styles and Psychobiological Distress Among Adolescents Affected by a Large-Scale Disaster  

Microsoft Academic Search

The authors examined the relations between mobilizing coping, the tendency for families to respond to problems by seeking community-based assistance, and psychological distress and cortisol activity in homeless adolescents (12–17 years) who were displaced by Hurricane Katrina (n = 50) as compared to demographically matched controls (n = 31). Perceptions of family mobilizing covaried with lower cortisol activity, a physiological

Jacob M. Vigil; David C. Geary

2009-01-01

248

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

SciTech Connect

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

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

1994-09-01

249

Analysis of two Arab families reveals additional support for a DFNB2 nonsyndromic phenotype of MYO7A.  

PubMed

Variants in the head and tail domains of the MYO7A gene, encoding myosin VIIA, cause Usher syndrome type 1B (USH1B) and nonsyndromic deafness (DFNB2, DFNA11). In order to identify the genetic defect(s) underling profound deafness in two consanguineous Arab families living in UAE, we have sequenced a panel of 19 genes involved in Usher syndrome and nonsyndromic deafness in the index cases of the two families. This analysis revealed a novel homozygous insertion of AG (c.1952_1953insAG/p.C652fsX11) in exon 17 of the MYO7A gene in an Iraqi family, and a homozygous point mutation (c.5660C>T/p.P1887L) in exon 41 affecting the same gene in a large Palestinian family. Moreover, some individuals from the Palestinian family also harbored a novel heterozygous truncating variant (c.1267C>T/p.R423X) in the DFNB31 gene, which is involved in autosomal recessive nonsyndromic deafness type DFNB31 and Usher syndrome type II. Assuming an autosomal recessive mode of inheritance in the two inbred families, we conclude that the homozygous variants in the MYO7A gene are the disease-causing mutations in these families. Furthermore, given the absence of retinal disease in all affected patients examined, particularly a 28 year old patient, suggests that at least one family may segregate a DFNB2 presentation rather than USH1B. This finding further supports the premise that the MYO7A gene is responsible for two distinct diseases and gives evidence that the p.P1887L mutation in a homozygous state may be responsible for nonsyndromic hearing loss. PMID:24194196

Ben-Salem, Salma; Rehm, Heidi L; Willems, Patrick J; Tamimi, Zakaria A; Ayadi, Hammadi; Ali, Bassam R; Al-Gazali, Lihadh

2014-01-01

250

Familial cavernous malformations in a large French kindred: mapping of the gene to the CCM1 locus on chromosome 7q  

PubMed Central

OBJECTIVES—To characterise clinically a large French family affected with cerebral cavernomas and to check for linkage of this condition to chromosome 7.?METHODS—A family, originating from Normandy and in which five members had undergone surgery for cavernomas, was extended. All members older than 18 were studied clinically and by neuroimaging. Genetic linkage analysis was conducted using 11 polymorphic microsatellite markers located between D7S502 and D7S479.?RESULTS—The family included three generations. Among the 25 members investigated, 11 had an abnormal cerebral MRI, eight of them being symptomatic, and 12 were asymptomatic with a normal MRI. The status of the two remaining members could not be established on the basis of clinical and MRI data. The family reported shares some striking features with other previously linked families—namely, a high clinical penetrance and the presence of multiple lesions within most of the affected members. A lod score of 4.04 was obtained with marker D7S657 with no recombinant. Significant lod scores were also obtained with D7S524 (Zmax=3.32 at ?=0.00) and D7S630 (Zmax=3.44 at ?=0.00). These results establish linkage of the condition found in this family to chromosome 7. Haplotype analysis strongly suggests that the gene is telomeric to D7S802 and centromeric to D7S479.?CONCLUSIONS—These data confirm linkage of cerebral cavernous malformations to chromosome 7 in a non-Hispanic family.?? PMID:9221966

Notelet, L; Chapon, F; Khoury, S; Vahedi, K; Chodkiewicz, J; Courtheoux, P; Iba-Zizen, M; Cabanis, E; Lechevalier, B; Tournier-Lasserve, E; Houtteville, J

1997-01-01

251

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

PubMed Central

A 44-year-old Albanian male was consulted and diagnosed with dementia. His magnetic resonance imaging suggested diffuse white matter changes. The suspicion of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was raised, and a genetic analysis confirmed such a suspicion through uncovering a pathogenic mutation at the level of exon 4 (c.475C>T) of chromosome 19. The patient came from a large family of 13 children, all of whom underwent clinical, genetic, and imaging examination. The pathogenic mutation was found present only in his eldest sister (50 years old), and she presented also very suggestive signs of CADASIL in her respective imaging study, but without any clinically significant counterpart. All other siblings were free from clinical and radiological signs of the disorder. Our opinion was that we were dealing with a mutation showing a very low level of penetrance, with only two siblings affected in a large Albanian family with 13 children. PMID:24124395

Vyshka, Gentian; Kruja, Jera

2013-01-01

252

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

Microsoft Academic Search

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

Xavier Rambla; Óscar Valiente; Carla Frías

2011-01-01

253

A Large Deletion Disrupts the Exon 3 Transcription Activation Domain of the BRCA2 Gene in a Breast\\/Ovarian Cancer Family1  

Microsoft Academic Search

We describe the identification of a large deletion in the BRCA2 gene as the disease-causing mutation in a Swedish breast\\/ovarian cancer family. The 5068-bp deletion encompassed the 3' region of exon 3, including the 3' splice site and most of intron 3, and it resulted on the niRNA level in an inframe exon 3 skipping. The junction site also included

Margarete Nordling; Yvonne Engwall; Arne Wallgren; Tommy Martinsson

1998-01-01

254

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

PubMed Central

Background WRKY genes encode one of the most abundant groups of transcription factors in higher plants, and its members regulate important biological process such as growth, development, and responses to biotic and abiotic stresses. Although the soybean genome sequence has been published, functional studies on soybean genes still lag behind those of other species. Results We identified a total of 133 WRKY members in the soybean genome. According to structural features of their encoded proteins and to the phylogenetic tree, the soybean WRKY family could be classified into three groups (groups I, II, and III). A majority of WRKY genes (76.7%; 102 of 133) were segmentally duplicated and 13.5% (18 of 133) of the genes were tandemly duplicated. This pattern was not apparent in Arabidopsis or rice. The transcriptome atlas revealed notable differential expression in either transcript abundance or in expression patterns under normal growth conditions, which indicated wide functional divergence in this family. Furthermore, some critical amino acids were detected using DIVERGE v2.0 in specific comparisons, suggesting that these sites have contributed to functional divergence among groups or subgroups. In addition, site model and branch-site model analyses of positive Darwinian selection (PDS) showed that different selection regimes could have affected the evolution of these groups. Sites with high probabilities of having been under PDS were found in groups I, II c, II e, and III. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. Conclusions In this work, all the WRKY genes, which were generated mainly through segmental duplication, were identified in the soybean genome. Moreover, differential expression and functional divergence of the duplicated WRKY genes were two major features of this family throughout their evolutionary history. Positive selection analysis revealed that the different groups have different evolutionary rates. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. PMID:24088323

2013-01-01

255

Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer's disease  

PubMed Central

Alzheimer's disease (AD) is a genetically complex disorder for which the definite diagnosis is only accomplished post mortem. Mutations in three genes (APP, PSEN1 and PSEN2) are known to cause AD, but a large number of familial cases do not harbor mutations in these genes and several unidentified genes that contain disease-causing mutations are thought to exist. We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family with a complex history of neurological and immunological disorders and identified a mutation in NOTCH3 (p.R1231C), previously described as causing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Complete screening of NOTCH3 in a cohort of 95 early onset AD cases and 95 controls did not reveal any additional pathogenic mutations. Although the complex history of disease in this family precluded us to establish segregation of the mutation found with disease, our results show that exome sequencing is a rapid, cost-effective and comprehensive tool to detect genetic mutations, allowing for the identification of unexpected genetic causes of clinical phenotypes. As etiological based therapeutics become more common, this method will be key in diagnosing and treating disease. PMID:22153900

Guerreiro, Rita Joao; Lohmann, Ebba; Kinsella, Emma; Bras, Jose Miguel; Luu, Nga; Gurulian, Nicole; Dursun, Burcu; Bilgi, Basar; Santana, Isabel; Hanagasi, Hasmet; Gurvit, Hakan; Gibbs, Raphael; Oliveira, Catarina; Emre, Murat; Singleton, Andrew

2011-01-01

256

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

PubMed Central

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

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

2012-01-01

257

Ras-like Small GTPases Form a Large Family of Proteins in the Marine Sponge Suberites domuncula  

Microsoft Academic Search

Sponges (Porifera) are the simplest and the most ancient metazoan animals, which branched off first from the common ancestor\\u000a of all multicellular animals. We have inspected ?13,000 partial cDNA sequences (ESTs) from the marine sponge Suberites domuncula and have identified full or partial cDNA sequences coding for ?50 different Ras-like small GTPases. Forty-four sponge proteins\\u000a from the Ras family are

Helena Cetkovic; Andreja Mikoc; Werner E. G. Müller; Vera Gamulin

2007-01-01

258

Skinfold over toenail is pathognomonic for the popliteal pterygium syndrome in a Congolese family with large intrafamilial variability  

PubMed Central

Key Clinical Message We report on three related Congolese popliteal pterygium syndrome (PPS) patients concordant only for the skinfold over the toenail. Mutation analysis revealed that the three affected individuals carried a heterozygous missense mutation in the Exon 4, NM_006147.2:c.250C>T; p.Arg84Cys. This is the first molecularly confirmed PPS family from central Africa. PMID:25548624

Mubungu, Gerrye; Lumaka, Aimé; Matondo, Rosette; Mbayabo, Gloire; Tuka, Deborah; Kayembe, Claudarche; Mulowhe, Didier; Molua, Antoine; Tady, Bruno-Paul; Nkidiaka, Emmanuel; Bunga, Paulo; Lukusa Tshilobo, Prosper; Devriendt, Koenraad

2014-01-01

259

Familial Mediterranean fever in children: report of a large series and discussion of the risk and prognostic factors of amyloidosis  

Microsoft Academic Search

Familial Mediterranean fever (FMF) is a genetically transmitted disease characterized by recurrent attacks of fever and serositis.\\u000a The most important complication of this disease is the development of amyloidosis. We present our analysis of 425 FMF patients\\u000a without and 180 with amyloidosis (123 FMF having amyloidosis type I and 57 FMF having amyloidosis type II). The male\\/female\\u000a ratio was higher

Ü. Saatçi; S. Ozen; S. Özdemir; A. Bakkaloglu; N. Besbas; R. Topaloglu; S. Arslan

1997-01-01

260

Whole exome sequencing identifies new causative mutations in Tunisian families with non-syndromic deafness.  

PubMed

Identification of the causative mutations in patients affected by autosomal recessive non syndromic deafness (DFNB forms), is demanding due to genetic heterogeneity. After the exclusion of GJB2 mutations and other mutations previously reported in Tunisian deaf patients, we performed whole exome sequencing in patients affected with severe to profound deafness, from four unrelated consanguineous Tunisian families. Four biallelic non previously reported mutations were identified in three different genes: a nonsense mutation, c.208C>T (p.R70X), in LRTOMT, a missense mutation, c.5417T>C (p.L1806P), in MYO15A and two splice site mutations, c.7395+3G>A, and c.2260+2T>A, in MYO15A and TMC1 respectively. We thereby provide evidence that whole exome sequencing is a powerful, cost-effective screening tool to identify mutations causing recessive deafness in consanguineous families. PMID:24926664

Riahi, Zied; Bonnet, Crystel; Zainine, Rim; Louha, Malek; Bouyacoub, Yosra; Laroussi, Nadia; Chargui, Mariem; Kefi, Rym; Jonard, Laurence; Dorboz, Imen; Hardelin, Jean-Pierre; Salah, Sihem Belhaj; Levilliers, Jacqueline; Weil, Dominique; McElreavey, Kenneth; Boespflug, Odile Tanguy; Besbes, Ghazi; Abdelhak, Sonia; Petit, Christine

2014-01-01

261

Identification of three novel ECEL1 mutations in three families with distal arthrogryposis type 5D.  

PubMed

Arthrogryposis refers to congenital contracture in at least two different body parts. When distal joints are primarily involved, the term distal arthrogryposis (DA) is used. The recognition of clinically distinct subtypes of DA has proven very useful in mapping the disease genes for this genetically heterogeneous condition. DA5D is characterized by ocular involvement usually in the form of ptosis and incomitant strabismus, but extraocular manifestations have also been reported. In a multiplex consanguineous family with DA5D, we combined autozygosity mapping and exome sequencing to identify a novel mutation in ECEL1. This was followed by targeted sequencing of this gene in another two extended consanguineous family with the same phenotype, which revealed two additional novel homozygous mutations. Our results support the recent identification of mutations in ECEL1 as a disease gene in DA5D and expand the clinical and allelic spectrum of this condition. PMID:23829171

Shaheen, R; Al-Owain, M; Khan, A O; Zaki, M S; Hossni, H A A; Al-Tassan, R; Eyaid, W; Alkuraya, F S

2014-06-01

262

Whole Exome Sequencing Identifies New Causative Mutations in Tunisian Families with Non-Syndromic Deafness  

PubMed Central

Identification of the causative mutations in patients affected by autosomal recessive non syndromic deafness (DFNB forms), is demanding due to genetic heterogeneity. After the exclusion of GJB2 mutations and other mutations previously reported in Tunisian deaf patients, we performed whole exome sequencing in patients affected with severe to profound deafness, from four unrelated consanguineous Tunisian families. Four biallelic non previously reported mutations were identified in three different genes: a nonsense mutation, c.208C>T (p.R70X), in LRTOMT, a missense mutation, c.5417T>C (p.L1806P), in MYO15A and two splice site mutations, c.7395+3G>A, and c.2260+2T>A, in MYO15A and TMC1 respectively. We thereby provide evidence that whole exome sequencing is a powerful, cost-effective screening tool to identify mutations causing recessive deafness in consanguineous families. PMID:24926664

Zainine, Rim; Louha, Malek; Bouyacoub, Yosra; Laroussi, Nadia; Chargui, Mariem; Kefi, Rym; Jonard, Laurence; Dorboz, Imen; Hardelin, Jean-Pierre; Salah, Sihem Belhaj; Levilliers, Jacqueline; Weil, Dominique; McElreavey, Kenneth; Boespflug, Odile Tanguy; Besbes, Ghazi; Abdelhak, Sonia; Petit, Christine

2014-01-01

263

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

SciTech Connect

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

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

1996-01-15

264

Immunoglobulin heavy chain variable region and major histocompatibility region genes are linked to induced graves' disease in females from two very large families of recombinant inbred mice.  

PubMed

Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

McLachlan, Sandra M; Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W; Rapoport, Basil

2014-10-01

265

Patterns of divergence of a large family of nodule cysteine-rich peptides in accessions of Medicago truncatula  

PubMed Central

The nodule cysteine-rich (NCR) groups of defensin-like (DEFL) genes are one of the largest gene families expressed in the nodules of some legume plants. They have only been observed in the inverted repeat loss clade (IRLC) of legumes, which includes the model legume Medicago truncatula. NCRs are reported to play an important role in plant–microbe interactions. To understand their diversity we analyzed their expression and sequence polymorphisms among four accessions of M. truncatula. A significant expression and nucleotide variation was observed among the genes. We then used 26 accessions to estimate the selection pressures shaping evolution among the accessions by calculating the nucleotide diversity at non-synonymous and synonymous sites in the coding region. The mature peptides of the orthologous NCRs had signatures of both purifying and diversifying selection pressures, unlike the seed DEFLs, which predominantly exhibited purifying selection. The expression, sequence variation and apparent diversifying selection in NCRs within the Medicago species indicates rapid and recent evolution, and suggests that this family of genes is actively evolving to adapt to different environments and is acquiring new functions. PMID:24635121

Nallu, Sumitha; Silverstein, Kevin A T; Zhou, Peng; Young, Nevin D; VandenBosch, Kathryn A

2014-01-01

266

Utility of STR markers for the molecular diagnosis of a large Brazilian family with Charcot-Marie-Tooth disease.  

PubMed

Charcot-Marie-Tooth type 1A disease (CMT1A) is most frequently caused by a tandem DNA duplication of a 1.4-Mb genomic fragment in the 17p11.2-12 chromosomal region. The disease is probably the product of a dosage effect of the peripheral myelin protein 22 gene located within the duplicated segment. We sought to study the largest reported Brazilian family with suspected diagnosis of CMT1A using eight short tandem repeat microsatellite markers. In addition, we analyzed the informativeness of these markers in the normal Brazilian population. The duplication was found in 12 members of the family. In two patients with CMT1A symptoms, the duplication was not detected, and one asymptomatic subject showed the duplication. D17S2230, D17S9B, D17S2220, D17S2227, D17S9A, and D17S4A markers showed the highest heterozygosity rates, and D17S2228 and D17S2224 markers were the least informative in our analysis. PMID:19048496

Possamai, C O; Carvalho, F M; Silva, M F C; Wolfgramm, E V; Sartori, M P N; Malta, F S V; Ribeiro, V P; Spina, V P; Gomes, K B; Ferreira, A C S; Louro, I D

2008-01-01

267

First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer  

PubMed Central

Background CHEK2 is a multi-cancer susceptibility gene whose common germline mutations are known to contribute to the risk of developing breast and prostate cancer. Case presentation Here, we describe an Italian family with a high number of cases of breast cancer and other types of tumour subjected to the MLPA test to verify the presence of BRCA1, BRCA2 and CHEK2 deletions and duplications. We identified a new 23-kb duplication in the CHEK2 gene extending from intron 5 to 13 that was associated with breast cancer in the family. The presence and localisation of the alteration was confirmed by a second analysis by Next-Generation Sequencing. Conclusions This finding suggests that CHEK2 mutations are heterogeneous and that techniques other than sequencing, such as MLPA, are needed to identify CHEK2 mutations. It also indicates that CHEK2 rare variants, such as duplications, can confer a high susceptibility to cancer development and should thus be studied in depth as most of our knowledge of CHEK2 concerns common mutations. PMID:24986639

2014-01-01

268

Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families  

Microsoft Academic Search

BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0–36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and\\/or ovarian cancer patients in whom a deleterious mutation in BRCA1 and BRCA2 was not detected by sequencing

Thomas v. O. Hansen; Lars Jønson; Anders Albrechtsen; Mette K. Andersen; Bent Ejlertsen; Finn C. Nielsen

2009-01-01

269

Screening for large rearrangements of the BRCA2 gene in Spanish families with breast\\/ovarian cancer  

Microsoft Academic Search

Germ-line mutations in BRCA1 and BRCA2 are responsible for about 30–60% of the hereditary breast and ovarian cancer (HBOC). A large number of point mutations have\\u000a been described in both genes. However, large deletions and duplications that disrupt one or more exons are overlooked by point\\u000a mutation detection approaches. Over the past years several rearrangements have been identified in BRCA1,

Sara Gutiérrez-Enríquez; Miguel de La Hoya; Cristina Martínez-Bouzas; Ana Sanchez de Abajo; Teresa Ramón y Cajal; Gemma Llort; Ignacio Blanco; Elena Beristain; Eduardo Díaz-Rubio; Carmen Alonso; María-Isabel Tejada; Trinidad Caldés; Orland Diez

2007-01-01

270

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

Microsoft Academic Search

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

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

2009-01-01

271

Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p.F29L in KCNH2  

PubMed Central

Background Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering?>?90% of cases, are KCNQ1, KCNH2 and SCN5A. Methods We describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2. Results Twenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 “unrelated” families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of?large founder family with p.F29L in KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis. PMID:24606995

2014-01-01

272

A clinical evaluation tool for SNP arrays, especially for autosomal recessive conditions in offspring of consanguineous parents  

PubMed Central

Purpose: This report describes a fast online tool to accelerate and improve clinical interpretation of single nucleotide polymorphism array results for diagnostic purposes, when consanguinity or inbreeding is identified. Methods: We developed a web-based program that permits entry of regions of homozygosity and, using OMIM, UCSC, and NCBI databases, retrieves genes within these regions as well as their associated autosomal recessive disorders. Relevant OMIM Clinical Synopses can be searched, using key clinical terms permitting further filtering for candidate genes and disorders. Results: The tool aids the clinician by arriving at a short list of relevant candidate disorders, guiding the continued diagnostic work-up. Its efficacy is illustrated by presenting seven patients who were diagnosed using this tool. Conclusion: The online single nucleotide polymorphism array evaluation tool rapidly and systematically identifies relevant genes and associated conditions mapping to identified regions of homozygosity. The built-in OMIM clinical feature search allows the user to further filter to reach a short list of candidate conditions relevant for the diagnosis, making it possible to strategize more focused diagnostic testing. The tabulated results can be downloaded and saved to the desktop in an Excel format. Its efficacy is illustrated by providing a few clinical examples. PMID:23100014

Wierenga, Klaas J.; Jiang, Zhijie; Yang, Amy C.; Mulvihill, John J.; Tsinoremas, Nicholas F.

2013-01-01

273

Correlated Si isotope anomalies and large C-13 enrichments in a family of exotic SiC grains  

NASA Technical Reports Server (NTRS)

A hypothesis is presented to the effect that the distinctive morphological characteristics and comparatively simple Si isotope systematics identify the platy SiC crystals as a genetically related family, formed around a single isotopically heterogeneous presolar star on an association of related stars. The enrichments in C-13 and the Si isotope systematics of the platy SiC are broadly consistent with theoretical models of nucleosynthesis in low-mass, carbon stars on the ASG. The Si isotope array most plausibly reflects mixing between (Si-28)-rich material, inherited from a previous generation of stars, and material enriched in Si-29 and Si-30, produced in intershell regions by neutron capture during He-burning. The absence of a correlation between the Si and C isotopic compositions of the SiC suggests either episodic condensation of SiC, extending over several thermal pulses, in the atmosphere of a single star, or the derivation of the SiC from several stars characterized by different rates of C-13 production.

Stone, J.; Hutcheon, I. D.; Epstein, S.; Wasserburg, G. J.

1991-01-01

274

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

Microsoft Academic Search

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

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

2008-01-01

275

The large-conductance calcium-activated potassium channel holds the key to the conundrum of familial hypokalemic periodic paralysis  

PubMed Central

Purpose Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium (KCa) channel genes in HOKPP patients. Methods We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. Results Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the KCa channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes KCa1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. Conclusion These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels. PMID:25379045

Kim, Sung-Jo; Kang, Sun-Yang; Yi, Jin Woong; Kim, Seung-Min

2014-01-01

276

Two female siblings with West syndrome: Familial idiopathic West syndrome with genetic susceptibility and variable phenotypic expression.  

PubMed

The West syndrome (WS) is a characteristic form of epilepsy which usually begins in the first year of life. We describe two female siblings, aged 4 and 2 years, respectively, born from third degree consanguineous parents, with infantile spasms and developmental delay. Epileptic spasms had not a good outcome under antiepileptic drug treatment. Clinical and imaging features were of different severity in both siblings. Routine biochemical tests, metabolic investigations, and chromosomal analysis were normal. We analyzed CDKL5 gene by direct sequences and denaturing high-performance liquid chromatography using Transgenomic WAVE system. Analysis of the CDKL5 gene, which is responsible for female patient with WS, did not show any disease-causing mutation. WS has heterogeneous backgrounds, and may be more than one gene is responsible for its familial forms. In this family, consanguinity is observed in parents, which usually suggests that autosomal recessive inheritance is likely. PMID:21559165

Caglayan, Ahmet Okay; Gumus, Hakan; Kato, Mitsuhiro

2010-07-01

277

Two female siblings with West syndrome: Familial idiopathic West syndrome with genetic susceptibility and variable phenotypic expression  

PubMed Central

The West syndrome (WS) is a characteristic form of epilepsy which usually begins in the first year of life. We describe two female siblings, aged 4 and 2 years, respectively, born from third degree consanguineous parents, with infantile spasms and developmental delay. Epileptic spasms had not a good outcome under antiepileptic drug treatment. Clinical and imaging features were of different severity in both siblings. Routine biochemical tests, metabolic investigations, and chromosomal analysis were normal. We analyzed CDKL5 gene by direct sequences and denaturing high-performance liquid chromatography using Transgenomic WAVE system. Analysis of the CDKL5 gene, which is responsible for female patient with WS, did not show any disease-causing mutation. WS has heterogeneous backgrounds, and may be more than one gene is responsible for its familial forms. In this family, consanguinity is observed in parents, which usually suggests that autosomal recessive inheritance is likely. PMID:21559165

Caglayan, Ahmet Okay; Gumus, Hakan; Kato, Mitsuhiro

2010-01-01

278

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

PubMed

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

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

2011-01-01

279

Identification of Rare Recurrent Copy Number Variants in High-Risk Autism Families and Their Prevalence in a Large ASD Population  

PubMed Central

Structural variation is thought to play a major etiological role in the development of autism spectrum disorders (ASDs), and numerous studies documenting the relevance of copy number variants (CNVs) in ASD have been published since 2006. To determine if large ASD families harbor high-impact CNVs that may have broader impact in the general ASD population, we used the Affymetrix genome-wide human SNP array 6.0 to identify 153 putative autism-specific CNVs present in 55 individuals with ASD from 9 multiplex ASD pedigrees. To evaluate the actual prevalence of these CNVs as well as 185 CNVs reportedly associated with ASD from published studies many of which are insufficiently powered, we designed a custom Illumina array and used it to interrogate these CNVs in 3,000 ASD cases and 6,000 controls. Additional single nucleotide variants (SNVs) on the array identified 25 CNVs that we did not detect in our family studies at the standard SNP array resolution. After molecular validation, our results demonstrated that 15 CNVs identified in high-risk ASD families also were found in two or more ASD cases with odds ratios greater than 2.0, strengthening their support as ASD risk variants. In addition, of the 25 CNVs identified using SNV probes on our custom array, 9 also had odds ratios greater than 2.0, suggesting that these CNVs also are ASD risk variants. Eighteen of the validated CNVs have not been reported previously in individuals with ASD and three have only been observed once. Finally, we confirmed the association of 31 of 185 published ASD-associated CNVs in our dataset with odds ratios greater than 2.0, suggesting they may be of clinical relevance in the evaluation of children with ASDs. Taken together, these data provide strong support for the existence and application of high-impact CNVs in the clinical genetic evaluation of children with ASD. PMID:23341896

Christensen, G. Bryce; Kim, Cecilia; Frackelton, Edward; Thomas, Kelly; da Silva, Renata Pellegrino; Stevens, Jeff; Baird, Lisa; Otterud, Brith; Ho, Karen; Varvil, Tena; Leppert, Tami; Lambert, Christophe G.; Leppert, Mark; Hakonarson, Hakon

2013-01-01

280

The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene  

PubMed Central

Background Members of the makorin (mkrn) gene family encode RING/C3H zinc finger proteins with U3 ubiquitin ligase activity. Although these proteins have been described in a variety of eukaryotes such as plants, fungi, invertebrates and vertebrates including human, almost nothing is known about their structural and functional evolution. Results Via partial sequencing of a testis cDNA library from the poeciliid fish Xiphophorus maculatus, we have identified a new member of the makorin gene family, that we called mkrn4. In addition to the already described mkrn1 and mkrn2, mkrn4 is the third example of a makorin gene present in both tetrapods and ray-finned fish. However, this gene was not detected in mouse and rat, suggesting its loss in the lineage leading to rodent murids. Mkrn2 and mkrn4 are located in large ancient duplicated regions in tetrapod and fish genomes, suggesting the possible involvement of ancestral vertebrate-specific genome duplication in the formation of these genes. Intriguingly, many mkrn1 and mkrn2 intronless retrocopies have been detected in mammals but not in other vertebrates, most of them corresponding to pseudogenes. The nature and number of zinc fingers were found to be conserved in Mkrn1 and Mkrn2 but much more variable in Mkrn4, with lineage-specific differences. RT-qPCR analysis demonstrated a highly gonad-biased expression pattern for makorin genes in medaka and zebrafish (ray-finned fishes) and amphibians, but a strong relaxation of this specificity in birds and mammals. All three mkrn genes were maternally expressed before zygotic genome activation in both medaka and zebrafish early embryos. Conclusion Our analysis demonstrates that the makorin gene family has evolved through large-scale duplication and subsequent lineage-specific retroposition-mediated duplications in vertebrates. From the three major vertebrate mkrn genes, mkrn4 shows the highest evolutionary dynamics, with lineage-specific loss of zinc fingers and even complete gene elimination from certain groups of vertebrates. Comparative expression analysis strongly suggests that the ancestral E3 ubiquitin ligase function of the single copy mkrn gene before duplication in vertebrates was gonad-specific, with maternal expression in early embryos. PMID:21172006

2010-01-01

281

The Community of Family Circles (CFC) algorithm: a new inversion approach to obtaining self-consitent 4D thermal histories from large, spatially distributed thermochronological data sets  

NASA Astrophysics Data System (ADS)

One of the most significant advances in interpreting thermochronological data is arguably our ability to extract information about the rate and trajectory of cooling over a range of temperatures, rather than having to rely on the veracity of the simplification of assuming a single closure temperature specified by a rate of monotonic cooling. Modern thermochronometry data, such as apatite fission track and (U-Th)/He analysis, are particularly good examples of data amenable to this treatment as acceptably well calibrated kinetic models now exist for both systems. With ever larger data sets of this type being generated over ever larger areas the prospect of inverting very large amounts of such data distributed spatially over large areas offers new possibilities for constraining the thermal and erosional histories over length scales approximating whole orogens and sub-continents. The challenge though is in how to properly deal with joint inversion of multiple samples in a self-consistent manner while also utilising all the available information contained in the data. We describe a new approach to this problem, called the Community of Family Circles (CFC) algorithm, which extracts information from spatially distributed apatite fission track ages (AFT) and track length distributions (TLD). The method is based on the rationale that the 3D geothermal field of the crust varies smoothly through space and time because of the efficiency of thermal diffusion. Our approach consists of seeking groups of spatially adjacent samples, or families, within a given circular radius for which a common thermal history is appropriate. The temperature offsets between individual time-temperature paths are determined relative to a low-pass filtered topographic surface, whose shape is assumed to mimic the shape of the isotherms in the partial annealing zone. This enables a single common thermal history to be shared, or interpolated, between the family members while still honouring the individual samples temperature offset requirements. The geothermal gradient can be either treated as a parameter in the inversion scheme or evaluated when local vertical profile or heat flow measurements are available. As data for each sample is inverted several times with different subsets, or as a member of different families, we then extract the subset with the lowest misfit and assign that sample to its respective ''family'' whose optimum time-temperature path is subsequently assigned to the sample. We thus obtain a set of thermal histories (one for each sample) which can then be interpolated to obtain exhumation rates or maximum temperature maps. We demonstrate our approach on a variety of synthetic datasets, generated for different geomorphologies and sampling densities, using the 3D thermal Pecube code in order to test the resolution and limits of the method. The approach is then applied to a 600 by 600 km area in northern Namibia where an extensive apatite fission track dataset including ages and track length distributions is available. We finally discuss extension of the technique to multiple thermochronometers. We also discuss possible future modifications and strategies for improving the flexibility and computational efficiency and effectiveness of the method.

Beucher, R.; Brown, R. W.

2013-12-01

282

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

NASA Astrophysics Data System (ADS)

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

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

2007-12-01

283

Comparative Analysis of P450 Signature Motifs EXXR and CXG in the Large and Diverse Kingdom of Fungi: Identification of Evolutionarily Conserved Amino Acid Patterns Characteristic of P450 Family  

PubMed Central

Cytochrome P450 monooxygenases (P450s) are heme-thiolate proteins distributed across the biological kingdoms. P450s are catalytically versatile and play key roles in organisms primary and secondary metabolism. Identification of P450s across the biological kingdoms depends largely on the identification of two P450 signature motifs, EXXR and CXG, in the protein sequence. Once a putative protein has been identified as P450, it will be assigned to a family and subfamily based on the criteria that P450s within a family share more than 40% homology and members of subfamilies share more than 55% homology. However, to date, no evidence has been presented that can distinguish members of a P450 family. Here, for the first time we report the identification of EXXR- and CXG-motifs-based amino acid patterns that are characteristic of the P450 family. Analysis of P450 signature motifs in the under-explored fungal P450s from four different phyla, ascomycota, basidiomycota, zygomycota and chytridiomycota, indicated that the EXXR motif is highly variable and the CXG motif is somewhat variable. The amino acids threonine and leucine are preferred as second and third amino acids in the EXXR motif and proline and glycine are preferred as second and third amino acids in the CXG motif in fungal P450s. Analysis of 67 P450 families from biological kingdoms such as plants, animals, bacteria and fungi showed conservation of a set of amino acid patterns characteristic of a particular P450 family in EXXR and CXG motifs. This suggests that during the divergence of P450 families from a common ancestor these amino acids patterns evolve and are retained in each P450 family as a signature of that family. The role of amino acid patterns characteristic of a P450 family in the structural and/or functional aspects of members of the P450 family is a topic for future research. PMID:24743800

Syed, Khajamohiddin; Mashele, Samson Sitheni

2014-01-01

284

Role of family susceptibility, occupational and family histories and individuals' blood groups in the development of silicosis.  

PubMed Central

A previous investigation has shown that family susceptibility and occupational and family histories have a decisive role in the development of byssinosis among workers exposed to flax dust. Results of investigation of silicosis in 814 male workers exposed to silica-bearing dust showed that family susceptibility has an important role in the development of silicosis among examined workers, and workers whose fathers had an occupational history of exposure to silica-bearing dust were more resistant to the development of the disease than those with non-exposed fathers. The degree of consanguinity of parents and individuals' blood groups, also, have a role. Workers with cousin parents were relatively highly susceptible to the development of silicosis as well as workers with blood groups "O" or "AB". It has been concluded that the investigated factors might have a role in the development of other occupational diseases and further investigations are indicated. PMID:6255981

Noweir, M H; Moselhi, M; Amine, E K

1980-01-01

285

Familial systemic lupus erythematosus: the role of genetic and environmental factors  

PubMed Central

Objective: To examine the contribution of genetic and environmental factors to disease occurrence in 26 families with two or more members affected with systemic lupus erythematosus (SLE). Methods: Genetic and environmental factors were examined by HLA-A, B, C/DR typing and by determining the presence of lymphocytotoxic antibodies (LCA) in patients and their consanguineous and non-consanguineous relatives. Results: No association between SLE and HLA-A, B, C antigens was found. There was, however, a significant association with HLA-DR2 in white subjects with SLE. The most striking finding was that HLA sharing was increased among the affected members, suggesting genetic similarities. Seven of 14 sib pairs (50%) who had concordant SLE were HLA identical as opposed to an expected 25%. Another interesting finding was that 15/18 (83%) patients with SLE and 11/22 (50%) consanguineous relatives had LCA, while 1/9 (11%) spouses, and 2/42 (5%) healthy controls had these antibodies. Conclusion: Genetic factors have a role in the development and expression of SLE. Environmental factors may trigger the disease in genetically susceptible hosts. PMID:11779754

Eroglu, G; Kohler, P

2002-01-01

286

An autosomal recessive form of spastic cerebral palsy (CP) with microcephaly and mental retardation  

Microsoft Academic Search

Cerebral palsy (CP) is defined as any nonprogressive motor deficits resulting from cerebral abnormalities that occur in the prenatal or perinatal period. Symptoms become apparent during the first year of life. Genetic forms of CP account for about 2% in European populations but are thought to cause a substantial proportion in consanguineous families. We have identified a large consanguineous family

Anna Rajab; Seung-Yun Yoo; Aiman Abdulgalil; Salem Kathiri; Riaz Ahmed; Ganeshwaran H. Mochida; Adria Bodell; A. James Barkovich; Christopher A. Walsh

2006-01-01

287

Crizotinib (PF-2341066) induces apoptosis due to downregulation of pSTAT3 and BCL-2 family proteins in NPM-ALK+ anaplastic large cell lymphoma  

PubMed Central

Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is an aberrant fusion gene product with tyrosine kinase activity and is expressed in substantial subset of anaplastic large cell lymphomas (ALCL). It has been shown that NPM-ALK binds to and activates signal transducer and activator of transcription 3 (STAT3). Although NPM-ALK+ ALCL overall shows a better prognosis, there is a sub-group of patients who relapses and is resistant to conventional chemotherapeutic regimens. NPM-ALK is a potential target for small molecule kinase inhibitors. Crizotinib (PF-2341066) is a small, orally bioavailable molecule that inhibits growth of tumors with ALK activity as shown in a subgroup of non-small lung cancer patients with EML4-ALK expression. In this study, we have investigated the in vitro effects of Crizotinib in ALCL cell line with NPM-ALK fusion. Crizotinib induced marked downregulation of STAT3 phosphorylation, which was associated with significant apoptotic cell death. Apoptosis induction was attributed to caspase-3 cleavage and marked downregulation of the Bcl-2 family of proteins including MCL-1. These findings implicate that Crizotinib has excellent potential to treat patients with NPM-ALK+ ALCL through induction of apoptotic cell death and downregulation of major oncogenic proteins in this aggressive lymphoma. PMID:24486291

Hamedani, Farid Saei; Cinar, Munevver; Mo, Zhicheng; Cervania, Melissa A.; Amin, Hesham M.; Alkan, Serhan

2015-01-01

288

Estimation of Modified Concordance Ratio in Sib-Pairs: Effect of Consanguinity on the Risk of Congenital Heart Diseases  

Microsoft Academic Search

Family studies are widely used for research into genetic and environmental influences on human traits. In this paper, we establish statistical methodology for the estimation of a new measure of sib similarity with respect to dichotomous traits measured on each member of within family sib-pair. We call this parameter \\

Mohamed M. Shoukri; Allan Donner; Nadia Abdalla Dessouky; Shazia Subhani; Mansour Al-Joufan; Ahmed Al-Omrani; Futwan Al-Mohanna; Zohair Y. Al Halees

2010-01-01

289

Leaf rust resistance gene Lr1, isolated from bread wheat (Triticum aestivum L.) is a member of the large psr567 gene family.  

PubMed

In hexaploid wheat, leaf rust resistance gene Lr1 is located at the distal end of the long arm of chromosome 5D. To clone this gene, an F(1)-derived doubled haploid population and a recombinant inbred line population from a cross between the susceptible cultivar AC Karma and the resistant line 87E03-S2B1 were phenotyped for resistance to Puccinia triticina race 1-1 BBB that carries the avirulence gene Avr1. A high-resolution genetic map of the Lr1 locus was constructed using microsatellite, resistance gene analog (RGA), BAC end (BE), and low pass (LP) markers. A physical map of the locus was constructed by screening a hexaploid wheat BAC library from cultivar Glenlea that is known to have Lr1. The locus comprised three RGAs from a gene family related to RFLP marker Xpsr567. Markers specific to each paralog were developed. Lr1 segregated with RGA567-5 while recombinants were observed for the other two RGAs. Transformation of the susceptible cultivar Fielder with RGA567-5 demonstrated that it corresponds to the Lr1 resistance gene. In addition, the candidate gene was also confirmed by virus-induced gene silencing. Twenty T (1) lines from resistant transgenic line T (0)-938 segregated for resistance, partial resistance and susceptibility to Avr1 corresponding to a 1:2:1 ratio for a single hemizygous insertion. Transgene presence and expression correlated with the phenotype. The resistance phenotype expressed by Lr1 seemed therefore to be dependant on the zygosity status. T (3)-938 sister lines with and without the transgene were further tested with 16 virulent and avirulent rust isolates. Rust reactions were all as expected for Lr1 thereby providing additional evidence toward the Lr1 identity of RGA567-5. Sequence analysis of Lr1 indicated that it is not related to the previously isolated Lr10 and Lr21 genes and unlike these genes, it is part of a large gene family. PMID:17611798

Cloutier, Sylvie; McCallum, Brent D; Loutre, Caroline; Banks, Travis W; Wicker, Thomas; Feuillet, Catherine; Keller, Beat; Jordan, Mark C

2007-09-01

290

Human KZNF Gene Catalog - A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors  

DOE Data Explorer

Kruppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets. [This abstract was copied from: S Huntley, DM Baggott, AT Hamilton, M Tran-Gyamfi, S Yang, J Kim, L Gordon, E Branscomb, and L Stubbs. 2006. A comprehensive catalog of human KRAB-associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors, Genome Research 16(5):669 - 677] The website provides the ability to search the online catalog by genomic coordinates, name, locus type, and motifs, to utilize a graphical browser and to download data files.

Huntley, S; Baggott, D.M.; Hamilton, A.T.; Tran-Gyamfi, M.; Yang, S.; Kim, J.; Gordon, L.; Branscomb, E.; Stubbs, L.

291

Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q  

SciTech Connect

Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North American kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.

Fink, J.K.; Wu, C.T.B.; Jones, S.M.

1994-09-01

292

Variable myopathic presentation in a single family with novel skeletal RYR1 mutation.  

PubMed

We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax?=?3.86 at ??=?0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca(2+) stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient's muscle concomitant with a reduction of the DHPR?1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies. PMID:23894444

Attali, Ruben; Aharoni, Sharon; Treves, Susan; Rokach, Ori; Becker Cohen, Michal; Fellig, Yakov; Straussberg, Rachel; Dor, Talya; Daana, Muhannad; Mitrani-Rosenbaum, Stella; Nevo, Yoram

2013-01-01

293

HOST FAMILY PROGRAM Host family: ____________________________________ Family No. _________  

E-print Network

HOST FAMILY PROGRAM Host family: ____________________________________ Family No. _________ Student: 13 January ­ 28 May 2003 THE FAMILY PROVIDES THE STUDENT WITH: 1. Three meals daily all week long. (If a student should arrive home too late for a meal, the family should leave the prepared meal

294

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

Microsoft Academic Search

Background: Manually finding subtle yet statistically significant links to distantly related homologues becomes practically impossible for very populated protein families due to the sheer number of similarity searches to be invoked and analyzed. The unclear evolutionary relationship between classical mammalian lipases and the recently discovered human adipose triglyceride lipase (ATGL; a patatin family member) is an exemplary case for such

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

2006-01-01

295

Apogossypolone, a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins, effectively inhibits growth of diffuse large cell lymphoma cells in vitro and in vivo.  

PubMed

Apogossypolone (ApoG2) is a semi-synthesized derivative of gossypol. The principal objective of this study was to compare stability and toxicity between ApoG2 and gossypol, and to evaluate anti-lymphoma activity of ApoG2 in vitro and in vivo. ApoG2 shows better stability when compared with a racemic gossypol and can be better tolerated by mice compared to gossypol. ApoG2 showed significant inhibition of cell proliferation of WSU-DLCL(2) and primary cells obtained from lymphoma patients, whereas it displayed no toxicity on normal peripheral blood lymphocytes. For a treatment of 72 h, the IC(50) of ApoG2 was determined to be 350 nM against WSU-DLCL2 cells. Treatment with ApoG2 at 600 mg/kg resulted in significant growth inhibition of WSU-DLCL(2) xenografts. When combined with CHOP, ApoG2 displayed even more complete inhibition of tumor growth. ApoG2 binds to purified recombinant Bcl-2, Mcl-1 and Bcl-X(L) proteins with high affinity and is shown to block the formation of heterodimers between Bcl-X(L) and Bim. For a treatment of 72 h, ApoG2 induced a maximum of 32% of apoptotic cell death. Western blot experiments showed that treatment with ApoG2 led to cleavage of caspase-3, caspase-9 and PARP. Moreover, pretreatment of DLCL(2) cells with caspase-3, -9 and broad spectrum caspase inhibitors significantly blocked growth inhibition induced by ApoG2. In conclusion, ApoG2 effectively inhibits growth of DLCL(2) cells at least partly by inducing apoptosis. It is an attractive small molecule inhibitor of the Bcl-2 family proteins to be developed further for the treatment of diffuse large cell lymphoma. PMID:18769131

Sun, Yuan; Wu, Jack; Aboukameel, Amro; Banerjee, Sanjeev; Arnold, Alan A; Chen, Jianyong; Nikolovska-Coleska, Zaneta; Lin, Yanqiong; Ling, Xiaolan; Yang, Dajun; Wang, Shaomeng; Al-Katib, Ayad; Mohammad, Ramzi M

2008-09-01

296

The relationship between family history, gender role attitudes, and susceptibility to gender inequitable perceptions of family and family member functioning  

Microsoft Academic Search

This research examined how family roles, gender of family leadership, beliefs about the consequences of maternal employment, and family history of parental division of responsibility related to young adults' perceptions of family and individual family member functioning. One hundred seven (107), predominantly Anglo American undergraduate students completing courses in educational psychology at a large midwestern university rated two videotaped family

David C. Ivey; Tamara Yaktus

1996-01-01

297

A Novel Splice-Site Mutation in ALS2 Establishes the Diagnosis of Juvenile Amyotrophic Lateral Sclerosis in a Family with Early Onset Anarthria and Generalized Dystonias  

PubMed Central

The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes. PMID:25474699

Vu, Anthony; Azim, Saad; Silver, David L.; Mansoor, Atika; Tay, Stacey Kiat Hong; Abbasi, Sumiya; Hashmi, Asraf Hussain; Janjua, Jamal; Khalid, Sumbal; Tai, E. Shyong; Yeo, Gene W.; Khor, Chiea Chuen

2014-01-01

298

Identification of a New Intronic BMPR2-Mutation and Early Diagnosis of Heritable Pulmonary Arterial Hypertension in a Large Family with Mean Clinical Follow-Up of 12 Years  

PubMed Central

Background Mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene can lead to hereditary pulmonary arterial hypertension (HPAH) and are detected in more than 80% of cases with familial aggregation of the disease. Factors determining disease penetrance are largely unknown. Methods A mean clinical follow-up of 12 years was accomplished in 46 family members including echocardiography, stress-Dopplerechocardiography and genetic analysis of TGF-? pathway genes. Right heart catheterization and RNA-analysis was performed in members with pathological findings. Results Manifest HPAH was diagnosed in 8 members, 4 were already deceased, two died during the follow-up, two are still alive. Normal pulmonary artery systolic pressure at rest but hypertensive response to exercise has been identified in 19 family members. Analysis of BMPR2 transcripts revealed aberrant splicing due to an insertion of an intronic Alu element adjacent to exon 6. All HPAH patients and 12 further asymptomatic family members carried this insertion. During follow-up two family members carrying hypertensive response and the Alu insertion developed manifest HPAH. Conclusion This is the first report of an intronic BMPR2 mutation due to an Alu element insertion causing HPAH in a large family which has been confirmed on RNA-level. Only those members that carried both hypertensive response and the mutation developed manifest HPAH during follow-up. Our findings highlight the importance of including further methods such as RNA analysis into the molecular genetic diagnostic of PAH patients. They suggest that at least in some families hypertensive response may be an additional risk factor for disease manifestation and penetrance. PMID:24621962

Pfarr, Nicole; Szamalek-Hoegel, Justyna; Lichtblau, Mona; Nagel, Christian; Egenlauf, Benjamin; Ehlken, Nicola; Grünig, Ekkehard

2014-01-01

299

A novel nonsense mutation in keratin 10 causes a familial case of recessive epidermolytic ichthyosis  

PubMed Central

Epidermolytic ichthyosis (EI) is a rare skin disorder characterized by generalized erythroderma and cutaneous blistering at birth, which is substituted by hyperkeratosis later in life. It is caused by autosomal dominant mutations in highly conserved regions of KRT1 and KRT10. To date, only four mutations with autosomal recessive inheritance of EI have been described in consanguineous families. All of them affect the 2B domain of KRT10. In the present study, we describe four patients with EI (including one lethal case) born from unaffected parents in a consanguineous family of a native Venezuelan community. The objective of this study was to characterize the clinical, genetic, and morphological aspects of the disease in this family, as well as understand its functional implications. Genomic DNA was sequenced for KRT10 and KRT1. Immunofluoresence for keratin expression was performed on cutaneous biopsies. After examination of cutaneous biopsies histology, our results showed hyperkeratosis and acantholysis with an expanded granular layer. Sequencing of KRT10 demonstrated a nonsense mutation (p.Tyr282Ter.) corresponding to the 1B domain of the protein in patients and a heterozygous pattern in other family members, resulting in complete absence of K10. The loss of K10 was compensated by upregulation of K14 and K17. In conclusion, this novel mutation in KRT10 is the first recessive genetic variation that is not located in the so called “hot spot” for recessive EI, suggesting that other areas of the gene are also susceptible for such mutations. PMID:23957016

Gutierrez, Jeydith A; Hannoush, Zeina C; Vargas, Luis G; Momany, Allison; Garcia, Carmen C; Murray, Jeffrey C; Dunnwald, Martine

2013-01-01

300

Families with Daughters, Families with Sons: Different Challenges for Family Relationships and Marital Satisfaction?  

Microsoft Academic Search

In a longitudinal study, the links between family relations and marital relations were examined in families with early adolescent children. Over the course of 4 years, 128 mother–father–adolescent triads were investigated annually. They completed questionnaires assessing family climate and marital relationships. Longitudinal analyses revealed that the initially large discrepancies between adolescents' and their parents' perceptions of family cohesion, support, and

Inge Seiffge-Krenke

1999-01-01

301

Association of Monoclonal Expansion of Epstein-Barr Virus-Negative CD158a+ NK Cells Secreting Large Amounts of Gamma Interferon with Hemophagocytic Lymphohistiocytosis?  

PubMed Central

We report the first case of hemophagocytic lymphohistiocytosis (HLH) induced by the monoclonal expansion of Epstein-Barr virus (EBV)-negative NK cells. Consanguinity of the patient's parents made it necessary to discard familial HLH in the patient and her sister with identical HLA markers and demonstrate that no cause other than the expansion of NK cells, which secrete high levels of gamma interferon, was inducing HLH in this patient. PMID:19020108

López-Álvarez, María R.; Martínez-Sánchez, María V.; Salgado-Cecilia, María G.; Campillo, José A.; Heine-Suñer, Damian; Villar-Permuy, Florentina; Fuster, José L.; Bas, Águeda; Gil-Herrera, Juana; Muro, Manuel; García-Alonso, Ana M.; Álvarez-López, María R.; Minguela, Alfredo

2009-01-01

302

Association of monoclonal expansion of Epstein-Barr virus-negative CD158a+ NK cells secreting large amounts of gamma interferon with hemophagocytic lymphohistiocytosis.  

PubMed

We report the first case of hemophagocytic lymphohistiocytosis (HLH) induced by the monoclonal expansion of Epstein-Barr virus (EBV)-negative NK cells. Consanguinity of the patient's parents made it necessary to discard familial HLH in the patient and her sister with identical HLA markers and demonstrate that no cause other than the expansion of NK cells, which secrete high levels of gamma interferon, was inducing HLH in this patient. PMID:19020108

López-Alvarez, María R; Martínez-Sánchez, María V; Salgado-Cecilia, María G; Campillo, José A; Heine-Suñer, Damian; Villar-Permuy, Florentina; Fuster, José L; Bas, Agueda; Gil-Herrera, Juana; Muro, Manuel; García-Alonso, Ana M; Alvarez-López, María R; Minguela, Alfredo

2009-01-01

303

Autosomal dominant Kufs` disease: Clinical heterogeneity in nine families, and exclusion of linkage to CLN1 and CLN3 markers in a large American kindred  

SciTech Connect

Most forms of neuronal ceroid lipofuscinosis (NCL) are autosomal recessive, and three genes have already been mapped: the infantile form (CLN 1); the juvenile form (CLN 3); and the early juvenile variant (CLN 5) on chromosomes 1, 16 and 13, respectively. Kufs` disease or adolescent-adult onset NCL is usually inherited as an autosomal recessive trait, and presents as three distinct clinical syndromes: progressive myoclonus epilepsy (PME) with onset in the early teens or around age 30; and onset of dementia with motor disability in the 30s. We have studied three families originating from different parts of the USA manifesting dominantly inherited Kufs` disease. Granular osmophilic deposits (GROD) were found in brain, but storage in skin was not an obligatory feature. Six dominantly inherited PME families have been ascertained from three different regions of Spain. No storage was found in skin or muscle in any of these families. The mean age of onset in the American families is earlier, the clinical manifestations more severe, and the progression much more rapid that in the Spanish families. These findings would suggest the possibility of genetic heterogeneity involving two or more loci, or different mutations at the same gene locus. Genetic linkage studies have been carried out in a six-generation New Jersey family in an attempt to characterize the gene(s) responsible for this disorder. The infantile NCL locus on chromosome 1p (CLN1) and the juvenile NCL locus on chromosome 16p (CLN 3) have been excluded in this family. Further clinical, pathological and molecular genetic studies should lead to the clarification of the diagnostic approaches in this disorder.

Andermann, F.; Andermann, E.; Carpenter, S. [and others

1994-09-01

304

Familial idiopathic small-bowel and colonic varices in three siblings.  

PubMed

Idiopathic small-bowel and colonic varices are a rare source of bleeding from the gastrointestinal tract. To date there are only eight published case series of familial idiopathic small-bowel and colonic varices. We present a case series detailing three affected siblings who presented with significant lower gastrointestinal bleeding and had multiple varices on endoscopy and imaging. Though not confirmed, consanguinity in the parents suggests an autosomal recessive mode of inheritance. We summarize the literature to date and describe our institution's experience of endoscopy, diagnostic imaging, and treatment in these patients. PMID:25036657

Boland, Paul; Leonard, Jennifer; Saunders, Michael; Bursey, Ford

2014-10-01

305

Linkage analysis in a large Swedish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 9q22.32–31.1  

PubMed Central

Background The best known hereditary colorectal cancer syndromes, familial adenomatous polyposis (FAP) and hereditary non?polyposis colorectal cancer (HNPCC), constitute about 2% of all colorectal cancers, and there are at least as many non?FAP, non?HNPCC cases where the family history suggests a dominantly inherited colorectal cancer risk. Recently, a locus on chromosome 9q22.2–31.2 was identified by linkage analysis in sib pairs with colorectal cancer or adenoma. Methods Linkage analysis for the suggested locus on chromosome 9 was carried out in an extended Swedish family. This family had previously been investigated but following the identification of adenomas in several previously unaffected family members, these subjects were now considered to be gene carriers. Results In the present study, we found linkage of adenoma and colorectal cancer to chromosome 9q22.32–31.1 with a multipoint LOD score of 2.4. We were also able to define the region for this locus to 7.9?cM between the markers D9S280 and D9S277. Conclusions Our result supports the presence of a susceptibility locus predisposing to adenoma and colorectal cancer in this chromosomal region. PMID:16467217

Skoglund, J; Djureinovic, T; Zhou, X?L; Vandrovcova, J; Renkonen, E; Iselius, L; Bisgaard, M L; Peltomäki, P; Lindblom, A

2006-01-01

306

Family Secrets  

Microsoft Academic Search

The purpose of this article is to provide an overview of the literature that reveals extensive classifications of the family secrets. The review includes definitions, comparisons of family secrecy to family privacy, types of family secrets, reasons why families avoid exposing certain activities, and factors contributing to the maintenance of a secret. The disclosing of hidden information is discussed with

NAIMA BROWN-SMITH

1998-01-01

307

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 ...

308

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

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…

Chen, Jennifer J.; de Groot Kim, Sonja

2014-01-01

309

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

ERIC Educational Resources Information Center

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

Mathews, Carol A.; Grados, Marco A.

2011-01-01

310

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

PubMed Central

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

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

2013-01-01

311

Attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members and the general population in a large city in Guangzhou, China  

PubMed Central

Purpose Stigma towards people with mental illness is believed to be widespread in low and middle income countries. Methods This study assessed the attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members of patients in a psychiatric facility and the general public using a standard 43-item survey (N?=?535). Exploratory factor analysis identified four distinctive attitudes which were then compared using Analysis of Covariance (ANCOVA) among the four groups, all with ties to the largest psychiatric facility in Guangzhou, China, adjusting for sociodemographic differences. Results Four uncorrelated factors expressed preferences for 1) community-based treatment, social integration and a biopsychosocial model of causation, 2) direct personal relationships with people with mental illness, 3) a lack of fear and positive views of personal interactions with people with mental illness, 4) disbelief in superstitious explanations of mental illness. Statistically significant differences favored community-based treatment and biopsychosocial causation (factor 1) among professional groups (psychiatrists and nurses) as compared with family members and the general public (p?family members, unexpectedly, showed far weaker personal preferences for direct personal relationships with people with mental illness than all three other groups (p?family members showed the least positive attitudes towards direct personal relationships with people with mental illness. These findings suggest support for a more extensive, formal system of care that gives family members some distance from the problems of their relatives and support in their care. PMID:25053975

2014-01-01

312

Asteroid Family Physical Properties  

E-print Network

An asteroid family is typically formed when a larger parent body undergoes a catastrophic collisional disruption, and as such family members are expected to show physical properties that closely trace the composition and mineralogical evolution of the parent. Recently a number of new datasets have been released that probe the physical properties of a large number of asteroids, many of which are members of identified families. We review these data sets and the composite properties of asteroid families derived from this plethora of new data. We also discuss the limitations of the current data, and the open questions in the field.

Masiero, Joseph; Kasuga, Toshihiro; Parker, Alex H

2015-01-01

313

A Novel GCAP1 Missense Mutation (L151F) in a Large Family with Autosomal Dominant Cone-Rod Dystrophy (adCORD)  

PubMed Central

Purpose To elucidate the phenotypic and biochemical characteristics of a novel mutation associated with autosomal dominant cone–rod dystrophy (adCORD). Methods Twenty-three family members of a CORD pedigree underwent clinical examinations, including visual acuity tests, standardized full-field ERG, and fundus photography. Genomic DNA was screened for mutations in GCAP1 exons using DNA sequencing and single-strand conformational polymorphism (SSCP) analysis. Function and stability of recombinant GCAP1-L151F were tested as a function of [Ca2+], and its structure was probed by molecular dynamics. Results Affected family members experienced dyschromatopsia, hemeralopia, and reduced visual acuity by the second to third decade of life. Electrophysiology revealed a nonrecordable photopic response with later attenuation of the scotopic response. Affected family members harbored a C?T transition in exon 4 of the GCAP1 gene, resulting in an L151F missense mutation affecting the EF hand motif 4 (EF4). This change was absent in 11 unaffected family members and in 100 unrelated normal subjects. GCAP1-L151F stimulation of photoreceptor guanylate cyclase was not completely inhibited at high physiological [Ca2+], consistent with a lowered affinity for Ca2+-binding to EF4. Conclusions A novel L151F mutation in the EF4 hand domain of GCAP1 is associated with adCORD. The clinical phenotype is characterized by early cone dysfunction and a progressive loss of rod function. The biochemical phenotype is best described as persistent stimulation of photoreceptor guanylate cyclase, representing a gain of function of mutant GCAP1. Although a conservative substitution, molecular dynamics suggests a significant change in Ca2+-binding to EF4 and EF2 and changes in the shape of L151F-GCAP1. PMID:15790869

Sokal, Izabela; Dupps, William J.; Grassi, Michael A.; Brown, Jeremiah; Affatigato, Louisa M.; Roychowdhury, Nirmalya; Yang, Lili; Filipek, Slawomir; Palczewski, Krzysztof; Stone, Edwin M.; Baehr, Wolfgang

2005-01-01

314

Penetrance of HNPCC-related cancers in a retrolective cohort of 12 large Newfoundland families carrying a MSH2 founder mutation: an evaluation using modified segregation models  

Microsoft Academic Search

BACKGROUND: Accurate risk (penetrance) estimates for associated phenotypes in carriers of a major disease gene are important for genetic counselling of at-risk individuals. Population-specific estimates of penetrance are often needed as well. Families ascertained from high-risk disease clinics provide substantial data to estimate penetrance of a disease gene, but these estimates must be adjusted for possible specific sources of bias.

Karen A Kopciuk; Yun-Hee Choi; Elena Parkhomenko; Patrick Parfrey; John McLaughlin; Jane Green; Laurent Briollais

2009-01-01

315

Family Privilege  

ERIC Educational Resources Information Center

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…

Seita, John R.

2014-01-01

316

Family Secrets and Family Environment  

Microsoft Academic Search

This study explored whether family secrecy might be a potential mediator of later adult psychological functioning in the offspring of the family. Results revealed that family secrecy was related to psychological well-being in adulthood. The number of potentially secretive events, as well as the negativity of the family environment were strongly associated with poorer psychological functioning.

Marianne F. Jahn

1995-01-01

317

Familial Amyloidosis Cutis Dyschromica in Three Siblings: Report from Indonesia  

PubMed Central

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

Hermawan, Melyawati; Rihatmadja, Rahadi; Sirait, Sondang Pandjaitan

2014-01-01

318

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

PubMed Central

Background The chromosomes of higher plants are littered with retrotransposons that, in many cases, constitute as much as 80% of plant genomes. Long terminal repeat retrotransposons have been especially successful colonizers of the chromosomes of higher plants and examinations of their function, evolution, and dispersal are essential to understanding the evolution of eukaryotic genomes. In soybean, several families of retrotransposons have been identified, including at least two that, by virtue of the presence of an envelope-like gene, may constitute endogenous retroviruses. However, most elements are highly degenerate and are often sequestered in regions of the genome that sequencing projects initially shun. In addition, finding potentially functional copies from genomic DNA is rare. This study provides a mechanism to surmount these issues to generate a consensus sequence that can then be functionally and phylogenetically evaluated. Results Diaspora is a multicopy member of the Ty3-gypsy-like family of LTR retrotransposons and comprises at least 0.5% of the soybean genome. Although the Diaspora family is highly degenerate, and with the exception of this report, is not represented in the Genbank nr database, a full-length consensus sequence was generated from short overlapping sequences using a combination of experimental and in silico methods. Diaspora is 11,737 bp in length and contains a single 1892-codon ORF that encodes a gag-pol polyprotein. Phylogenetic analysis indicates that it is closely related to Athila and Calypso retroelements from Arabidopsis and soybean, respectively. These in turn form the framework of an endogenous retrovirus lineage whose members possess an envelope-like gene. Diaspora appears to lack any trace of this coding region. Conclusion A combination of empirical sequencing and retrieval of unannotated Genome Survey Sequence database entries was successfully used to construct a full-length representative of the Diaspora family in Glycine max. Diaspora is presently the only fully characterized member of a lineage of putative plant endogenous retroviruses that contains virtually no trace of an extra coding region. The loss of an envelope-like coding domain suggests that non-infectious retrotransposons could swiftly evolve from infectious retroviruses, possibly by anomalous splicing of genomic RNA. PMID:15876351

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

2005-01-01

319

Large-Scale, Lineage-Specific Expansion of a Bric-a-Brac/Tramtrack/Broad Complex Ubiquitin-Ligase Gene Family in Rice[W  

PubMed Central

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

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

2007-01-01

320

Gaspra and Ida in families  

NASA Technical Reports Server (NTRS)

The Galileo flyby candidates 951 Gaspra and 243 Ida are both in families. The former is in a complex of families associated with 8 Flora and the latter is in the Koronis family. The Flora and the Koronis families are described. The Galileo spacecraft will have the opportunity to sample fragments from two types of impacts; one impact totally destroyed the parent body and the other left a large body behind. The types of Ss are also different, the colors of Gaspra and the other Ss in the complex of families near 8 Flora are much redder in U-V than Ida and the Ss of the Koronis family.

Williams, James G.

1992-01-01

321

Family History  

MedlinePLUS

... Home CDC 24/7: Saving Lives. Protecting People.™ Genomics All CDC Topics Search The CDC Note: Javascript ... visit this page: About CDC.gov . Public Health Genomics Genomics Family Health History Share Compartir Family History ...

322

Family Arguments  

MedlinePLUS

... Pediatric First Aid for Caregivers and Teachers (PedFACTs) Teaching Package HealthyChildren.org Post-it Notes Family Life Health Management - Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types ...

323

Family Meals  

MedlinePLUS

... Sports: Keeping Kids Safe Concussions: What to Know Family Meals KidsHealth > Parents > Nutrition & Fitness Center > Healthy Eating & ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

324

Foster Families  

MedlinePLUS

... child in another home. Continue Why Do Kids Live With Foster Families? Most often, a kid goes ... this stressful and emotional time. Why Do Kids Live With Foster Families? Most often, a kid goes ...

325

A Comprehensive Catalog of Human KRAB-associated Zinc Finger Genes: Insights into the Evolutionary History of a Large Family of Transcriptional Repressors  

SciTech Connect

Krueppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotic species. In mammals, most ZNF proteins comprise a single class of transcriptional repressors in which a chromatin interaction domain, called the Krueppel-associated box (KRAB) is attached to a tandem array of DNA-binding zinc-finger motifs. KRAB-ZNF loci are specific to tetrapod vertebrates, but have expanded dramatically in numbers through repeated rounds of segmental duplication to create a gene family with hundreds of members in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the human genome for key motifs and used them to construct and manually curate gene models. The resulting KRAB-ZNF gene catalog includes 326 known genes, 243 of which were structurally corrected by manual annotation, and 97 novel KRAB-ZNF genes; this single family therefore comprises 20% of all predicted human transcription factor genes. Many of the genes are alternatively spliced, yielding a total of 743 distinct predicted proteins. Although many human KRAB-ZNF genes are conserved in mammals, at least 136 and potentially more than 200 genes of this type are primate-specific including many recent segmental duplicates. KRAB-ZNF genes are active in a wide variety of human tissues suggesting roles in many key biological processes, but most member genes remain completely uncharacterized. Because of their sheer numbers, wide-ranging tissue-specific expression patterns, and remarkable evolutionary divergence we predict that KRAB-ZNF transcription factors have played critical roles in crafting many aspects of human biology, including both deeply conserved and primate-specific traits.

Huntley, S; Baggott, D M; Hamilton, A T; Tran-Gyamfi, M; Yang, S; Kim, J; Gordon, L; Branscomb, E; Stubbs, L

2005-09-30

326

Family Support.  

ERIC Educational Resources Information Center

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);…

Wieck, Colleen, Ed.; McBride, Marijo, Ed.

1990-01-01

327

Family therapy.  

PubMed

Another major force not letting us succeed in the treatment of diabetes remains right inside the patients home, their family members. Hence, it is important to know the perception of the close family members about this simple and strong tool in diabetes, 'insulin'. The drug is nearing its century, it has not fully being accepted gracefully even in todays electronic savvy society. So, we need to strongly discover the reason for its non-acceptance, while trials are out inventing new drugs. One vital thing that can change this attitude is increasing the understanding of this drug, insulin in depth to close people around the patient, the 'family'. Underestimating family's perception about disease and treatment for diabetes is detrimental to both diseased and the doctor. This consists of a biopsychosocial model; biological, psychological and social factors. Family forms the most important part of it. The strategies in family therapy include psychodynamic, structural, strategic, and cognitive-behavioral component. Diabetes has and will continue to rise, so will be the treatment options. From the clinicians side its to fix fasting first but from patients its fix family first. Family therapy demonstrates the importance of insulin initiation and maintenance in insulin naive patients, and continuation for others. The specific needs of such patients and their impact on family life are met with family therapy. Who needs family therapy? Benefits of family therapy and a case based approach is covered. PMID:24251191

Altamash, Shaikh

2013-10-01

328

Family grief  

Microsoft Academic Search

Grief traditionally has been described from the individual perspective. In contrast, this article presents a family systems perspective on death and grieving. A group of interconnected individuals forming a system, defined as a “family,” reciprocally affect one another in response to internal or external events. Minuchin's structural theory emphasizes the importance of subsystems within a family; boundaries between subsystems are

Carol Michler Detmer; Joseph W. Lamberti

1991-01-01

329

Families affected by deafness: hospital services uptake in a multiethnic population  

PubMed Central

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

Yoong, S; Feltbower, R; Spencer, N; McKinney, P

2005-01-01

330

Two novel mutations in myosin binding protein C slow causing distal arthrogryposis type 2 in two large Han Chinese families may suggest important functional role of immunoglobulin domain C2.  

PubMed

Distal arthrogryposes (DAs) are a group of disorders that mainly involve the distal parts of the limbs and at least ten different DAs have been described to date. DAs are mostly described as autosomal dominant disorders with variable expressivity and incomplete penetrance, but recently autosomal recessive pattern was reported in distal arthrogryposis type 5D. Mutations in the contractile genes are found in about 50% of all DA patients. Of these genes, mutations in the gene encoding myosin binding protein C slow MYBPC1 were recently identified in two families with distal arthrogryposis type 1B. Here, we described two large Chinese families with autosomal dominant distal arthrogryposis type 2(DA2) with incomplete penetrance and variable expressivity. Some unique overextension contractures of the lower limbs and some distinctive facial features were present in our DA2 pedigrees. We performed follow-up DNA sequencing after linkage mapping and first identified two novel MYBPC1 mutations (c.1075G>A [p.E359K] and c.956C>T [p.P319L]) responsible for these Chinese DA2 families of which one introduced by germline mosacism. Each mutation was found to cosegregate with the DA2 phenotype in each family but not in population controls. Both substitutions occur within C2 immunoglobulin domain, which together with C1 and the M motif constitute the binding site for the S2 subfragment of myosin. Our results expand the phenotypic spectrum of MYBPC1-related arthrogryposis multiplex congenita (AMC). We also proposed the possible molecular mechanisms that may underlie the pathogenesis of DA2 myopathy associated with these two substitutions in MYBPC1. PMID:25679999

Li, Xuefu; Zhong, Bomeng; Han, Weitian; Zhao, Ning; Liu, Wei; Sui, Yu; Wang, Yawen; Lu, Yongping; Wang, Hong; Li, Jianxin; Jiang, Miao

2015-01-01

331

A novel type of class I gene organization in vertebrates: a large family of non-MHC-linked class I genes is expressed at the RNA level in the amphibian Xenopus.  

PubMed Central

A Xenopus class I cDNA clone, isolated from a cDNA expression library using antisera, is a member of a large family of non-classical class I genes (class Ib) composed of at least nine subfamilies, all of which are expressed at the RNA level. The subfamilies are well conserved in their immunoglobulin-like alpha 3 domains, but their peptide-binding regions (PBRs) and cytoplasmic domains are very divergent. In contrast to the great allelic diversity found in the PBR of classical class I genes, the alleles of one of the Xenopus non-classical subfamilies are extremely well conserved in all regions. Several of the invariant amino acids essential for the anchoring of peptides in the classical class I groove are not conserved in some subfamilies, but the class Ib genes are nevertheless more closely related in the PBR to classical and non-classical genes linked to the MHC in mammals and birds than to any other described class I genes like CD1 and the neonatal rat intestinal Fc receptor. Comparison with the Xenopus MHC-linked class Ia protein indicate that amino acids presumed to interact with beta 2-microglobulin are identical or conservatively changed in the two major class I families. Genomic analyses of Xenopus species suggest that the classical and non-classical families diverged from a common ancestor before the emergence of the genus Xenopus over 100 million years ago; all of the non-classical genes appear to be linked on a chromosome distinct from the one harboring the MHC. We hypothesize that this class Ib gene family is under very different selection pressures from the classical MHC genes, and that each subfamily may have evolved for a particular function. Images PMID:8223448

Flajnik, M F; Kasahara, M; Shum, B P; Salter-Cid, L; Taylor, E; Du Pasquier, L

1993-01-01

332

Two Novel Mutations in Myosin Binding Protein C Slow Causing Distal Arthrogryposis Type 2 in Two Large Han Chinese Families May Suggest Important Functional Role of Immunoglobulin Domain C2  

PubMed Central

Distal arthrogryposes (DAs) are a group of disorders that mainly involve the distal parts of the limbs and at least ten different DAs have been described to date. DAs are mostly described as autosomal dominant disorders with variable expressivity and incomplete penetrance, but recently autosomal recessive pattern was reported in distal arthrogryposis type 5D. Mutations in the contractile genes are found in about 50% of all DA patients. Of these genes, mutations in the gene encoding myosin binding protein C slow MYBPC1 were recently identified in two families with distal arthrogryposis type 1B. Here, we described two large Chinese families with autosomal dominant distal arthrogryposis type 2(DA2) with incomplete penetrance and variable expressivity. Some unique overextension contractures of the lower limbs and some distinctive facial features were present in our DA2 pedigrees. We performed follow-up DNA sequencing after linkage mapping and first identified two novel MYBPC1 mutations (c.1075G>A [p.E359K] and c.956C>T [p.P319L]) responsible for these Chinese DA2 families of which one introduced by germline mosacism. Each mutation was found to cosegregate with the DA2 phenotype in each family but not in population controls. Both substitutions occur within C2 immunoglobulin domain, which together with C1 and the M motif constitute the binding site for the S2 subfragment of myosin. Our results expand the phenotypic spectrum of MYBPC1-related arthrogryposis multiplex congenita (AMC). We also proposed the possible molecular mechanisms that may underlie the pathogenesis of DA2 myopathy associated with these two substitutions in MYBPC1. PMID:25679999

Li, Xuefu; Zhong, Bomeng; Han, Weitian; Zhao, Ning; Liu, Wei; Sui, Yu; Wang, Yawen; Lu, Yongping; Wang, Hong; Li, Jianxin; Jiang, Miao

2015-01-01

333

ORIGINAL ARTICLE Familial steroid-sensitive nephrotic syndrome  

E-print Network

. Consanguinity. Nephrosis . Lipoid . Arabs . Jews Abbreviations B bedouin FSGS focal segmental glomerulosclerosis;focal segmental glomerulosclerosis (FSGS), laminin-beta-2 [4], transient receptor potential cation

Friedman, Nir

334

Identification of an extensive gene cluster among a family of PPOs in Trifolium pratense L. (red clover) using a large insert BAC library  

PubMed Central

Background Polyphenol oxidase (PPO) activity in plants is a trait with potential economic, agricultural and environmental impact. In relation to the food industry, PPO-induced browning causes unacceptable discolouration in fruit and vegetables: from an agriculture perspective, PPO can protect plants against pathogens and environmental stress, improve ruminant growth by increasing nitrogen absorption and decreasing nitrogen loss to the environment through the animal's urine. The high PPO legume, red clover, has a significant economic and environmental role in sustaining low-input organic and conventional farms. Molecular markers for a range of important agricultural traits are being developed for red clover and improved knowledge of PPO genes and their structure will facilitate molecular breeding. Results A bacterial artificial chromosome (BAC) library comprising 26,016 BAC clones with an average 135 Kb insert size, was constructed from Trifolium pratense L. (red clover), a diploid legume with a haploid genome size of 440–637 Mb. Library coverage of 6–8 genome equivalents ensured good representation of genes: the library was screened for polyphenol oxidase (PPO) genes. Two single copy PPO genes, PPO4 and PPO5, were identified to add to a family of three, previously reported, paralogous genes (PPO1–PPO3). Multiple PPO1 copies were identified and characterised revealing a subfamily comprising three variants PPO1/2, PPO1/4 and PPO1/5. Six PPO genes clustered within the genome: four separate BAC clones could be assembled onto a predicted 190–510 Kb single BAC contig. Conclusion A PPO gene family in red clover resides as a cluster of at least 6 genes. Three of these genes have high homology, suggesting a more recent evolutionary event. This PPO cluster covers a longer region of the genome than clusters detected in rice or previously reported in tomato. Full-length coding sequences from PPO4, PPO5, PPO1/5 and PPO1/4 will facilitate functional studies and provide genetic markers for plant breeding. PMID:19619287

2009-01-01

335

What makes a family reliable?  

NASA Technical Reports Server (NTRS)

Asteroid families are clusters of asteroids in proper element space which are thought to be fragments from former collisions. Studies of families promise to improve understanding of large collision events and a large event can open up the interior of a former parent body to view. While a variety of searches for families have found the same heavily populated families, and some searches have found the same families of lower population, there is much apparent disagreement between proposed families of lower population of different investigations. Indicators of reliability, factors compromising reliability, an illustration of the influence of different data samples, and a discussion of how several investigations perceived families in the same region of proper element space are given.

Williams, James G.

1992-01-01

336

Reading Comprehension in a Large Cohort of French First Graders from Low Socio-Economic Status Families: A 7-Month Longitudinal Study  

PubMed Central

Background The literature suggests that a complex relationship exists between the three main skills involved in reading comprehension (decoding, listening comprehension and vocabulary) and that this relationship depends on at least three other factors orthographic transparency, children’s grade level and socioeconomic status (SES). This study investigated the relative contribution of the predictors of reading comprehension in a longitudinal design (from beginning to end of the first grade) in 394 French children from low SES families. Methodology/Principal findings Reading comprehension was measured at the end of the first grade using two tasks one with short utterances and one with a medium length narrative text. Accuracy in listening comprehension and vocabulary, and fluency of decoding skills, were measured at the beginning and end of the first grade. Accuracy in decoding skills was measured only at the beginning. Regression analyses showed that listening comprehension and decoding skills (accuracy and fluency) always significantly predicted reading comprehension. The contribution of decoding was greater when reading comprehension was assessed via the task using short utterances. Between the two assessments, the contribution of vocabulary, and of decoding skills especially, increased, while that of listening comprehension remained unchanged. Conclusion/Significance These results challenge the ‘simple view of reading’. They also have educational implications, since they show that it is possible to assess decoding and reading comprehension very early on in an orthography (i.e., French), which is less deep than the English one even in low SES children. These assessments, associated with those of listening comprehension and vocabulary, may allow early identification of children at risk for reading difficulty, and to set up early remedial training, which is the most effective, for them. PMID:24250802

Gentaz, Edouard; Sprenger-Charolles, Liliane; Theurel, Anne; Colé, Pascale

2013-01-01

337

Family Treatment for Bipolar Disorder: Family Impairment by Treatment Interactions  

PubMed Central

Objective There is a clear need for psychosocial treatments to supplement pharmacotherapy for bipolar disorder. In this study, the efficacy of 2 forms of adjunctive family intervention were compared to pharmacotherapy alone. In addition to evaluating overall differences between treatments, a chief goal was to examine whether family impairment levels moderated the effects of family intervention on outcome. Method Ninety-two patients diagnosed with bipolar I disorder (according to DSM-III-R) were randomly assigned to receive (1) pharmacotherapy alone, (2) family therapy + pharmacotherapy, or (3) multi-family psychoeducational group + pharmacotherapy. Treatments and assessments continued for up to 28 months. Primary outcome measures were number of episodes per year and percentage of time symptomatic throughout the entire follow-up period. The study was conducted from September 1992 through March 1999. Results No significant main effects were found for treatment condition. Thus, for the total sample, the addition of a family intervention did not improve outcome. However, there were significant treatment condition by family impairment interactions (p < .05). In patients from families with high levels of impairment, the addition of a family intervention (family therapy or psychoeducational group) resulted in a significantly improved course of illness, particularly the number of depressive episodes (p <.01) and proportion of time spent in a depressive episode (p <.01). These effects were relatively large (Cohen d = 0.7–1.0), with patients receiving either family intervention having roughly half the number of depressive episodes and amount of time spent depressed as those receiving pharmacotherapy alone. In contrast, for patients from low-impairment families, the addition of a family intervention did not improve course of illness. Conclusions Our findings build on previous literature suggesting the importance of treatment matching within the mood disorders and suggest that the utility of adding family interventions for bipolar patients and their families may depend upon the family’s level of impairment. PMID:18363424

Miller, Ivan W.; Keitner, Gabor I.; Ryan, Christine E.; Uebelacker, Lisa A.; Johnson, Sheri L.; Solomon, David A.

2010-01-01

338

Exome sequencing identifies a novel and a recurrent BBS1 mutation in Pakistani families with Bardet-Biedl syndrome  

PubMed Central

Purpose To determine the genetic cause of Bardet-Biedl syndrome (BBS) in two consanguineous Pakistani families. Methods Clinical characterization of the affected individuals in both families was performed with ophthalmic examination, electroretinography, electrocardiography, and liver and renal profiling. Seventeen genes are known to be associated with BBS, so exome sequencing was preferred over candidate gene sequencing. One affected individual from both families was selected for exome sequencing. Segregation of the identified variants was confirmed with Sanger sequencing. Results Retinitis pigmentosa, obesity, and learning difficulties were present in the affected individuals in both families. In family A, a sixth finger (polydactyly) of the proband’s sister was removed by a surgical operation leaving a scar on the little finger. Polydactyly was also present in both affected individuals from family B. All diagnostic symptoms were characteristic of BBS in both families. In both affected individuals from family A, exome sequencing identified a novel homozygous mutation (c.47+1G>T) in BBS1 that inactivates the splice donor site at the end of exon 1. In family B, a previously reported mutation, c.442G>A; p.(Asp148Asn), was detected. Conclusions Exome sequencing is an efficient and cost-effective technique for identifying mutations in genetically heterogeneous diseases. In addition, intrafamilial phenotypic variability in family A argues for the modifying effect of other still unknown modifier alleles. PMID:23559858

Ajmal, Muhammad; Khan, Muhammad Imran; Neveling, Kornelia; Tayyab, Ali; Jaffar, Sulman; Sadeque, Ahmed; Ayub, Humaira; Abbasi, Nasir Mahmood; Riaz, Moeen; Micheal, Shazia; Gilissen, Christian; Ali, Syeda Hafiza Benish; Azam, Maleeha; Collin, Rob W. J.; Cremers, Frans P. M.

2013-01-01

339

Synthesis, structure, and magnetism of a family of heterometallic {Cu2Ln7} and {Cu4Ln12} (Ln = Gd, Tb, and Dy) complexes: the Gd analogues exhibiting a large magnetocaloric effect.  

PubMed

The syntheses, structures, and magnetic properties of two heterometallic Cu(II)-Ln(III) (Ln(III) = Gd, Tb, and Dy) families, utilizing triethanolamine and carboxylate ligands, are reported. The first structural motif displays a nonanuclear {Cu(II)2Ln(III)7} metallic core, while the second reveals a hexadecanuclear {Cu(II)4Ln(III)12} core. The differing nuclearities of the two families stem from the choice of carboxylic acid used in the synthesis. Magnetic studies show that the most impressive features are displayed by the {Cu(II)2Gd(III)7} and {Cu(II)4Gd(III)12} complexes, which display a large magnetocaloric effect, with entropy changes -?Sm = 34.6 and 33.0 J kg(-1) K(-1) at T = 2.7 and 2.9 K, respectively, for a 9 T applied field change. It is also found that the {Cu(II)4Dy(III)12} complex displays single-molecule magnet behavior, with an anisotropy barrier to magnetization reversal of 10.1 K. PMID:25494949

Langley, Stuart K; Moubaraki, Boujemaa; Tomasi, Corrado; Evangelisti, Marco; Brechin, Euan K; Murray, Keith S

2014-12-15

340

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 Geminiviridae for inclusion in the ICTV 8th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of vira...

341

FAMILY GEMINIVIRIDAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The International Committee on the Taxonomy of Viruses geminivirus study group has revised the description of the family Geminiviridae for inclusion in the ICTV 8th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of vi...

342

Family, Extended  

ERIC Educational Resources Information Center

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…

Patton, Jessica Rae

2006-01-01

343

The family planning service.  

PubMed

In 1978, 1,521,400 women in Great Britain obtained contraceptives through the National Health Service (NHS) family planning clinics, in 1980 the number was 1,468,000; likewise in 1978 2,118,313 women obtained them through general practitioners who offer a contraceptive service and in 1980 the number was also down, to 2,033,810. There has been little expansion in the provision of family planning clinics or the organization of extra sessions, contrasting with the expansion program of the Family Planning Association (FPA) when they largely had the responsibility of providing services, before 1974. Clinic sessions should be available for people of all ages but young people might respond better to separate, less formal arrangements. For children under age 16 the professional should persuade the child to involve the parents as soon as possible. Health visitors must be well trained in family planning to provide advice and support to patients. With the recent restructuring of Health Authorities, family planning services must not be cut in order to save money. The FPA must ask the government to reissue the May 1974 family planning service Memorandum of Guidance, and must write to those responsible for the supervision of family planning services in this regard. PMID:6550171

Arger, K

1983-01-01

344

Family Theory and Family Health Research  

PubMed Central

Different family theories can be applied to different aspects of how families experience health and illness. The family health and illness cycle describes the phases of a family's experience, beginning with health promotion and risk reduction, then family vulnerability and disease onset or relapse, family illness appraisal, family acute response, and finally family adaptation to illness and recovery. For each phase, specific family theories that are most appropriate for guiding family and health research are discussed. PMID:21229056

Doherty, William J.

1991-01-01

345

Family acholeplasmataceae (including phytoplasmas)  

Technology Transfer Automated Retrieval System (TEKTRAN)

The family Acholeplasmataceae was originally established to accommodate the genus Acholeplasma, comprising the mollicutes that could be cultivated without the supplement of cholesterol and that use UGA as a stop codon instead of coding for tryptophan. It was later shown that the phytoplasmas, a larg...

346

Mexican Immigrant Families: Relating Trauma and Family Cohesion  

Microsoft Academic Search

This article applies structural equation modeling techniques to explore the relationships between constructs related to family strength and cohesion, acculturation, and trauma symptoms. The study uses a purposive sample comprised of 122 immigrant men and women from the Mexican community based in a large midwestern metropolitan Area. The data were collected using standardized instruments: Family Adaptability and Cohesion Evaluation Scale

Shweta Singh; Marta Lundy; Maria Vidal de Haymes; Ana Caridad

2011-01-01

347

Familial abdominal aortic aneurysms: Collection of 233 multiplex families  

Microsoft Academic Search

Objective: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband. Subjects and Methods: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom

Helena Kuivaniemi; Hidenori Shibamura; Claudette Arthur; Ramon Berguer; C. William Cole; Tatu Juvonen; Ronald A. Kline; Raymond Limet; Gerry MacKean; Örjan Norrgård; Gerard Pals; Janet T. Powell; Pekka Rainio; Natzi Sakalihasan; Clarissa van Vlijmen-van Keulen; Alain Verloes; Gerard Tromp

2003-01-01

348

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (The Health Family Tree Study and the NHLBI Family Heart Study)  

Microsoft Academic Search

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family

Roger R Williams; Steven C Hunt; Gerardo Heiss; Michael A Province; Jeannette T Bensen; Millicent Higgins; Robert M Chamberlain; Joan Ware; Paul N Hopkins

2001-01-01

349

The Pfam protein families database  

Microsoft Academic Search

Pfam is a large collection of protein families and domains. Over the past 2 years the number of families in Pfam has doubled and now stands at 6190 (version 10.0). Methodology improvements for searching the Pfam collection locally as well as via the web are described. Other recent innovations include modelling of discontinuous domains allow- ing Pfam domain definitions to

Alex Bateman; Lachlan James M. Coin; Richard Durbin; Robert D. Finn; Volker Hollich; Sam Griffiths-jones; Ajay Khanna; Mhairi Marshall; Simon Moxon; Erik L. L. Sonnhammer; David J. Studholme; Corin Yeats; Sean R. Eddy

2004-01-01

350

Family Gibberichthyidae Parr 1933 gibberfishes  

Microsoft Academic Search

Gibberfishes are a small family of stephanoberycoid fishes known from a few specimens collected from tropical marine waters. The juveniles differ markedly from the adults. Body moderately robust in adults, deep in young specimens, compressed posteriorly. Head moderately large, with large mucous cavities on top of head separated by thin ridges; mucous cavities covered by thin skin. Eyes large in

Alexander N. Kotlyar

351

Family History  

MedlinePLUS

... Brain Aneurysm Statistics and Facts Seeking Medical Attention Pediatric Aneurysms Brain Aneurysm Causes and Risk Factors Family History Early Detection and Screening Unruptured Brain Aneurysms Subarachnoid Hemorrhage Treatment Options Aneurysm Complications Post ...

352

Tomorrow's Family  

ERIC Educational Resources Information Center

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)

Pickett, Robert S.

1977-01-01

353

Family Issues  

MedlinePLUS

... Bullying Prevention Preparedness Tips for Families Tips for First Responders Serving Victims of Crime Take Me Home Emergency Preparedness Related Links Safe and Sound Task Force Voices Blog DONATE BECOME A MEMBER ...

354

FAMILIES FIRST: Keys to Successful Family Functioning Family Roles  

E-print Network

FAMILIES FIRST: Keys to Successful Family Functioning Family Roles Rick Peterson, Extension or family status. An equal opportunity/affirmative action employer. Issued in furtherance of Cooperative. publication 350-093 Types of family Roles Family roles are the recurrent patterns of behavior by which

Liskiewicz, Maciej

355

Family Limitation  

PubMed Central

Dr Robert Smith surveys the history of birth control and sounds a warning for the future of mankind, if the population explosion is allowed to continue unchecked. He stresses the importance of the role of the general practitioner in the limitation of births. Sir Theodore Fox describes the work of the Family Planning Association and stresses that, increasingly, this is a specialist service covering all aspects of fertility. He also feels that the general practitioner has a role in family planning. PMID:5954261

Smith, Robert

1966-01-01

356

Veritas Asteroid Family Still Holds Secrets?  

NASA Astrophysics Data System (ADS)

Veritas asteroid family has been studied for about two decades. These studies have revealed many secrets, and a respectable knowledge about this family had been collected. Here I will present many of these results and review the current knowledge about the family. However, despite being extensively studied, Veritas family is still a mystery. This will be illustrated through the presentation of the most interesting open problems. Was there a secondary collision within this family? Does asteroid (490) Veritas belong to the family named after it? How large was the parent body of the family? Finally, some possible directions for future studies that aims to address these questions are discussed as well.

Novakovic, B.

2012-12-01

357

Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations  

PubMed Central

Purpose Autosomal recessive retinitis pigmentosa (arRP) is a genetically heterogeneous disease resulting in progressive loss of photoreceptors that leads to blindness. To date, 36 genes are known to cause arRP, rendering the molecular diagnosis a challenge. The aim of this study was to use homozygosity mapping to identify the causative mutation in a series of inbred families with arRP. Methods arRP patients underwent standard ophthalmic examination, Goldman perimetry, fundus examination, retinal OCT, autofluorescence measurement, and full-field electroretinogram. Fifteen consanguineous families with arRP excluded for USH2A and EYS were genotyped on 250 K SNP arrays. Homozygous regions were listed, and known genes within these regions were PCR sequenced. Familial segregation and mutation analyzes were performed. Results We found ten mutations, seven of which were novel mutations in eight known genes, including RP1, IMPG2, NR2E3, PDE6A, PDE6B, RLBP1, CNGB1, and C2ORF71, in ten out of 15 families. The patients carrying RP1, C2ORF71, and IMPG2 mutations presented with severe RP, while those with PDE6A, PDE6B, and CNGB1 mutations were less severely affected. The five families without mutations in known genes could be a source of identification of novel genes. Conclusions Homozygosity mapping combined with systematic screening of known genes results in a positive molecular diagnosis in 66.7% of families. PMID:24339724

Marzouka, Nour al Dain; Hebrard, Maxime; Manes, Gaël; Sénéchal, Audrey; Meunier, Isabelle; Hamel, Christian P.

2013-01-01

358

Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation  

PubMed Central

Myosin VIIA mutations have been associated with non-syndromic hearing loss (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and genetic analyzes of a consanguineous Iranian family segregating autosomal recessive non-syndromic hearing loss (ARNSHL). The hearing impairment was mapped to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A gene was completed. The Iranian family (L-1419) was shown to segregate a novel homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid substitution in the motor domain of the myosin VIIA protein. Since one affected family member had significantly less severe hearing loss we used a candidate approach to search for a genetic modifier. This novel MYO7A mutation is the first reported to cause DFNB2 in the Iranian population and this DFNB2 family is the first to be associated with a potential modifier. The absence of vestibular and retinal defects, and less severe low frequency hearing loss, is consistent with the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude this family has non-syndromic hearing loss (DFNB2) rather than Usher syndrome type 1B (USH1B), providing further evidence that these two diseases represent discrete disorders. PMID:20132242

Hildebrand, Michael S.; Thorne, Natalie P.; Bromhead, Catherine J.; Kahrizi, Kimia; Webster, Jennifer A.; Fattahi, Zohreh; Bataejad, Mojgan; Kimberling, William J.; Stephan, Dietrich; Najmabadi, Hossein; Bahlo, Melanie; Smith, Richard J.H.

2010-01-01

359

Homozygosity Mapping and Targeted Sanger Sequencing Reveal Genetic Defects Underlying Inherited Retinal Disease in Families from Pakistan  

PubMed Central

Background Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD). Methods We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide polymorphism (SNP) array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS) of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families. Results Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1. Conclusions Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future. PMID:25775262

Waheed, Nadia Khalida; Siddiqui, Sorath Noorani; Mustafa, Bilal; Ayub, Humaira; Ali, Liaqat; Ahmad, Shakeel; Micheal, Shazia; Hussain, Alamdar; Shah, Syed Tahir Abbas; Ali, Syeda Hafiza Benish; Ahmed, Waqas; Khan, Yar Muhammad; den Hollander, Anneke I.; Haer-Wigman, Lonneke; Collin, Rob W. J.; Khan, Muhammad Imran; Qamar, Raheel; Cremers, Frans P. M.

2015-01-01

360

Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping  

SciTech Connect

Homozygosity mapping is a powerful strategy for mapping rare recessive traits in children of consanguineous marriages. Practical applications of this strategy are currently limited by the inability of conventional linkage analysis software to compute, in reasonable time, multipoint LOD scores for pedigrees with inbreeding loops. We have developed a new algorithm for rapid multipoint likelihood calculations in small pedigrees, including those with inbreeding loops. The running time of the algorithm grows, at most, linearly with the number of loci considered simultaneously. The running time is not sensitive to the presence of inbreeding loops, missing genotype information, and highly polymorphic loci. We have incorporated this algorithm into a software package, MAPMAKER/HOMOZ, that allows very rapid multipoint mapping of disease genes in nuclear families, including homozygosity mapping. Multipoint analysis with dozens of markers can be carried out in minutes on a personal workstation. 23 refs., 4 figs., 1 tab.

Kruglyak, L.; Daly, M.J. [Whitehead Institute for Biomedical Research, Cambridge, MA (United States); Lander, E.S. [Whitehead Institute for Biomedical Research, Cambridge, MA (United States)]|[Massachusetts Institute of Technology, Cambridge, MA (United States)

1995-02-01

361

Family Hypnotherapy.  

ERIC Educational Resources Information Center

A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

Araoz, Daniel L.; Negley-Parker, Esther

1985-01-01

362

Family matters.  

PubMed

'Why do you want to know?' a nurse friend was recently asked when she phoned the ward to ask how her father was. He was very ill in his local hospital and she and the rest of the family were on tenterhooks, anxious for news. PMID:25827999

Bates, Jane

2015-04-01

363

FAMILY TYMOVIRIDAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

This article provides a brief review of the taxonomic structure, virion properties, genome organization and replication strategy, antigenic properties, and biological properties of viruses in the family Tymoviridae. Criteria for demarcation of genus and species are provided. A brief review of each...

364

Family Grouping.  

ERIC Educational Resources Information Center

This report describes an observational study of one family-grouped classroom, a system in which elementary school children remain with the same teacher for two or more years. The class was composed of junior kindergarten, senior kindergarten, and grade 1 pupils. Each child was observed over a period of one year. A detailed observation schedule,…

Young, Vivienne; Reich, Carol

365

Serving Families.  

ERIC Educational Resources Information Center

Parent Services Project (PSP), the first comprehensive program of resources and mental health activities for parents offered at child care centers in the San Francisco Bay Area (California), has expanded to centers in six states, serving over 19,000 families. This report describes the program's history, aims, and achievements, along with specific…

Link, Geoffrey; Beggs, Marjorie; Seiderman, Ethel

366

Family Child Care Licensing Study, 2002.  

ERIC Educational Resources Information Center

This report presents the findings of the 2002 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2001 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Children's Foundation, Washington, DC.

367

Family Child Care Licensing Study, 2000.  

ERIC Educational Resources Information Center

This report presents the findings of the 2000 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1999 study. Data on small family child care homes and group or large family child care homes are organized in 23 categories: (1) number of regulated homes; (2)…

Kelly, Nia, Comp.

368

Family Child Care Licensing Study, 2001.  

ERIC Educational Resources Information Center

This report presents the findings of the 2001 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2000 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Children's Foundation, Washington, DC.

369

Family Child Care Licensing Study, 2003.  

ERIC Educational Resources Information Center

This report presents the findings of the 2003 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2002 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Hollestelle, Kay; Koch, Pauline D.

370

The case of the missing Ceres family  

NASA Astrophysics Data System (ADS)

Ceres is unusual among large (>250 km) asteroids in lacking a dynamical family. We explore possible explanations, noting that its particularly large size and the ubiquity of families associated with other large asteroids makes avoidance of a sufficiently-sized collision by chance exceedingly unlikely. Current models of Ceres' thermal history and interior structure favor a differentiated object with an icy near-surface covered by an ?0.1-1 km lag deposit, which could result in a collisional family of diverse, predominately icy bodies. We predict that sublimation of an icy Ceres family would occur on timescales of hundreds of millions of years, much shorter than the history of the Solar System. Sublimation on a Ceres family body would be aided by a low non-ice fraction and a high average temperature, both of which would inhibit lag deposit development. Because there seems to be no likely mechanism for removing a rocky Ceres family, and because the formation of a Ceres family of some kind seems nearly statistically inevitable, the lack of a Ceres family is indirect but independent evidence for Ceres' differentiation. All of the other large asteroids lacking dynamical families (704 Interamnia, 52 Europa, and 65 Cybele) have spectral properties similar to Ceres, or otherwise suggesting ice at their surfaces. While other large asteroids with similar spectral properties do have families (24 Themis, 10 Hygiea, 31 Euphrosyne), their families are not well understood, particularly Hygiea.

Rivkin, Andrew S.; Asphaug, Erik; Bottke, William F.

2014-11-01

371

Family Therapy and Disturbed Families.  

ERIC Educational Resources Information Center

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…

Zuk, Gerald H., Ed.; Boszormenyi-Nagy, Ivan, Ed.

372

Family Therapy with Families Having Delinquent Offspring  

ERIC Educational Resources Information Center

Family therapy with families of delinquent children provokes a number of defensive maneuvers to avoid family involvement in solving their problems. Many families view delinquent behavior as others view psychopathology. The problem is to help the family deal with one another and work together. (Author)

Johnson, Thomas F.

1975-01-01

373

Family Caregivers  

Microsoft Academic Search

Caregiving an elder with cancer has the potential to be rewarding and meaningful but is often described as burdensome and\\u000a overwhelming because caregiver needs are frequently unmet. As the provision of care has transitioned from the hospital to\\u000a outpatient settings, family caregivers have take responsibility for the day-to-day care of their ill loved ones at home [1–4].\\u000a Despite the fact

Betty R. Ferrell; Polly Mazanec

374

A novel family of insect-selective peptide neurotoxins targeting insect large-conductance calcium-activated K+ channels isolated from the venom of the theraphosid spider Eucratoscelus constrictus.  

PubMed

Spider venoms are actively being investigated as sources of novel insecticidal agents for biopesticide engineering. After screening 37 theraphosid spider venoms, a family of three new "short-loop" inhibitory cystine knot insecticidal toxins (?-TRTX-Ec2a, ?-TRTX-Ec2b, and ?-TRTX-Ec2c) were isolated and characterized from the venom of the African tarantula Eucratoscelus constrictus. Whole-cell patch-clamp recordings from cockroach dorsal unpaired median neurons revealed that, despite significant sequence homology with other theraphosid toxins, these 29-residue peptides lacked activity on insect voltage-activated sodium and calcium channels. It is noteworthy that ?-TRTX-Ec2 toxins were all found to be high-affinity blockers of insect large-conductance calcium-activated K(+) (BK(Ca)) channel currents with IC(50) values of 3 to 25 nM. In addition, ?-TRTX-Ec2a caused the inhibition of insect delayed-rectifier K(+) currents, but only at significantly higher concentrations. ?-TRTX-Ec2a and ?-TRTX-Ec2b demonstrated insect-selective effects, whereas the homologous ?-TRTX-Ec2c also resulted in neurotoxic signs in mice when injected intracerebroventricularly. Unlike other theraphosid toxins, ?-TRTX-Ec2 toxins induce a voltage-independent channel block, and therefore, we propose that these toxins interact with the turret and/or loop region of the external entrance to the channel and do not project deeply into the pore of the channel. Furthermore, ?-TRTX-Ec2a and ?-TRTX-Ec2b differ from other theraphotoxins at the C terminus and positions 5 to 6, suggesting that these regions of the peptide contribute to the phyla selectivity and are involved in targeting BK(Ca) channels. This study therefore establishes these toxins as tools for studying the role of BK(Ca) channels in insects and lead compounds for the development of novel insecticides. PMID:21447641

Windley, Monique J; Escoubas, Pierre; Valenzuela, Stella M; Nicholson, Graham M

2011-07-01

375

Parents FamiliesGuide PARENT & FAMILY RESOURCES  

E-print Network

Parents FamiliesGuide #12;11 Contents: PARENT & FAMILY RESOURCES Welcome from Vice Presidents ---------- 2 Parents Program Welcome --------------- 3 Parents & Families Weekend Information ---------------------- 5 Partnering with Penn State ------------- 6 The Role of the Student ------------------- 6 Penn

Thompson, Anne

376

The Pfam Protein Families Database  

Microsoft Academic Search

Pfam is a large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the WWW in the UK at http:\\/\\/www.sanger.ac.uk\\/Software\\/Pfam\\/ , in Sweden at http:\\/\\/www.cgr.ki.se\\/Pfam\\/ and in the US at http:\\/\\/ pfam.wustl.edu\\/ . The latest version (4.3) of Pfam contains 1815 families. These Pfam families match 63% of proteins in SWISS-PROT 37 and TrEMBL

Alex Bateman; Ewan Birney; Richard Durbin; Sean R. Eddy; Kevin L. Howe; Erik L. L. Sonnhammer

2000-01-01

377

Family planning for travellers.  

PubMed

A public health nurse from London describes the customs of nomadic people in the British Isles, known as "travellers," as they affect provision of family planning services. Most are of British or Irish stock, some migrate and others live in caravan sites all year. Their traditions dictate that men work and women are housewives. Early, often arranged, marriage, early childbearing and large families are the norm. Sex and contraception are not considered appropriate for discussion between the sexes, or in the presence of children. Large families and financial hardship force many women to space pregnancies. Women often have to hide contraceptives from their husbands, difficult in conditions without privacy. Therefore they prefer IUDs, but some use oral contraceptives, although sometimes erratically because most are illiterate. Traveller women are usually unwilling to do self-examination, as needed with IUDs. They often have difficulty attending regular Pap smear clinics. Cervical cancer rates are high. They experience discrimination in clinics, and need extra care about modesty. It is worth while to take time to develop trust in the clinical relationship, to deal with the traveller woman's uneasy among outsiders. PMID:2286082

Rustom, A

1990-11-01

378

Roles within the Family  

MedlinePLUS

... family unit, and which rights, privileges, obligations, and roles are assigned to each family member. In most families parents are expected to be the leaders or executives of the family; children are expected to follow the ...

379

Single Parent Families  

MedlinePLUS

... Families > Single Parent Families Family Life Listen Single Parent Families Article Body Single parenthood can be one ... in the United States live with only one parent. Most single-parent situations result from divorce, but ...

380

DEPLOYMENT & THE MILITARY FAMILY  

E-print Network

1 DEPLOYMENT & THE MILITARY FAMILY NEW ORLEANS, LOUISIANA ACTIVE DUTY MILITARY FAMILY MEMBERS: THE FLEET AND FAMILY SUPPORT CENTER ................. 3 II. POINTS OF CONTACT (POC).............................................................................................. 3 III. HEALTH & MENTAL HEALTH RESOURCES FOR IMMEDIATE FAMILY MEMBERS OF ACTIVE DUTY MILITARY

381

Families Experiencing Homelessness  

MedlinePLUS

... which may compound the stress the family feels. Families experiencing homelessness: Are typically comprised of a mother ... of other women. The Relationship Between Homelessness and Family Separation: Families who have experienced homelessness have much ...

382

Homolog of the polymorphic 4q35 FSHD locus (p13E-11; D4F104S1) maps to 10qter; exclusion as a second FSHD locus in a large Danish family  

SciTech Connect

Facioscapulohumeral muscular dystrophy (FSHD) has been mapped to 4q35 and shown to be associated with deletions that are detectable using probe p13E-11 (D4104S1). These deletions reside within highly polymorphic restriction fragments (20-300 kb) which can normally only be resolved completely using pulsed-field gel electrophoresis (PFGE). Family studies showed that p13E-11 detects two non-allelic loci, only one of which originates from 4q35 origin. In 20 CEPH families, 8 individuals were identified showing a `small` EcoRI fragment detectable by conventional Southern blotting. Linkage analysis allowed assignment of these fragments to 10qter (D10S212 and D10S180) in all families tested. Since FSHD shows genetic heterogeneity, this second p13E-11 locus on 10qter became an interesting candidate as a second FSHD family did not provide evidence for linkage on chromosome 10qter.

Frants, R.R.; Bakker, E.; Vossen, R.H.A.M. [and others

1994-09-01

383

Congenital abnormalities and clinical features associated with Wilms' tumour: a comprehensive study from a centre serving a large population.  

PubMed

Altogether 156 children treated for Wilms' tumour (WT) between 1970 and 1998 were studied. Sixty-six children, selected only by their attendance at clinic, were carefully examined and the findings compared to those from a case note review of 90 children. Congenital abnormalities were present in 45% of the examined cohort, in 19% of the case notes review group and in 30% overall. Novel findings included the association of WT with Marshall Smith syndrome, developmental delay in 3 of 4 cases of WT (one bilateral) and 1 sibling from consanguineous Pakistani families and another sibling also had leukaemia. The possibility of rare DNA repair or cancer predisposing disorders among these 4 families requires further study. Careful examination and history taking of an unselected patient cohort revealed a higher than expected incidence of clinical abnormalities which may be overlooked if not specifically sought. PMID:17499987

Ng, A; Griffiths, A; Cole, T; Davison, V; Griffiths, M; Larkin, S; Parkes, S E; Mann, J R; Grundy, R G

2007-06-01

384

Chromosome 6-linked autosomal recessive early-onset Parkinsonism: linkage in European and Algerian families, extension of the clinical spectrum, and evidence of a small homozygous deletion in one family. The French Parkinson's Disease Genetics Study Group, and the European Consortium on Genetic Susceptibility in Parkinson's Disease.  

PubMed Central

The gene for autosomal recessive juvenile Parkinsonism (AR-JP) recently has been mapped to chromosome 6q25.2-27 in Japanese families. We have tested one Algerian and 10 European multiplex families with early-onset Parkinson disease for linkage to this locus, with marker D6S305. Homogeneity analysis provided a conditional probability in favor of linkage of >.9 in eight families, which were analyzed further with eight microsatellite markers spanning the 17-cM AR-JP region. Haplotype reconstruction for eight families and determination of the smallest region of homozygosity in two consanguineous families reduced the candidate interval to 11.3 cM. If the deletion of two microsatellite markers (D6S411 and D6S1550) that colocalize on the genetic map and that segregate with the disease in the Algerian family is taken into account, the candidate region would be reduced to <1 cM. These findings should facilitate identification of the corresponding gene. We have confirmed linkage of AR-JP, in European families and in an Algerian family, to the PARK2 locus. PARK2 appears to be an important locus for AR-JP in European patients. The clinical spectrum of the disease in our families, with age at onset <=58 years and the presence of painful dystonia in some patients, is broader than that reported previously. PMID:9634531

Tassin, J; Dürr, A; de Broucker, T; Abbas, N; Bonifati, V; De Michele, G; Bonnet, A M; Broussolle, E; Pollak, P; Vidailhet, M; De Mari, M; Marconi, R; Medjbeur, S; Filla, A; Meco, G; Agid, Y; Brice, A

1998-01-01

385

Family-centered rounds.  

PubMed

Family-centered rounds (FCRs) are multidisciplinary rounds that involve medical teams partnering with patients and families in daily medical decision-making. Multiple FCR benefits have been identified including improving patient satisfaction, communication, discharge planning, medical education, and patient safety. Main barriers to FCRs are variability in attending rounding, duration of rounds, physical constrains of large teams and small rooms, specific and sensitive patient conditions, and lack of training of residents, students, and faculty on how to conduct effective and effecient FCRs. In the last decade, many programs have incorporated FCRs into daily practice due to their multiple perceived benefits. Future FCRs should focus on better operationalizing of FCRs and reporting on objective outcomes measures such as improved communication, coordination, and patient satisfaction that are crucial for healthcare. PMID:25084715

Mittal, Vineeta

2014-08-01

386

Genetics of familial hypercholesterolemia.  

PubMed

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200-500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics. PMID:25712136

Brautbar, Ariel; Leary, Emili; Rasmussen, Kristen; Wilson, Don P; Steiner, Robert D; Virani, Salim

2015-04-01

387

Positive Family Functioning.  

ERIC Educational Resources Information Center

The persistence of the nuclear family as the primary social unit in the United States and most all other societies, especially complex ones, is a fact. Values shape the definition of family, especially the "good family," and the "great debate" of this period on family failure, family corruption and the family's near demise originates in…

Sussman, Marvin B.

388

Reclaiming Family Privilege  

ERIC Educational Resources Information Center

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

Seita, John

2012-01-01

389

FMLA: Family & Medical FLA: Family Leave Act  

E-print Network

FMLA: Family & Medical Leave Act FLA: Family Leave Act DVL: Domestic Violence Leave Faculty Sick Leave FCAL: Family Care Act Leave Parental Leave & Leave Without Salary Who is · Faculty (9 month calendar weeks during one academic year (26 calendar weeks if eligible for "Service Member Family Leave

Borenstein, Elhanan

390

First Report of a Novel Missense CLDN19 Mutations Causing Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis in a Chinese Family.  

PubMed

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder caused by mutations in the CLDN16 or CLDN19 genes, encoding claudin-16 and claudin-19 in the thick ascending limb of Henle's loop. In patients with claudin-19 mutations, severe ocular involvement (macular coloboma, pigmentary retinitis, nystagmus, or visual loss) has been described. In this report, we presented a 12-year-old girl with rickets, polyuria, and polydipsia. She was the daughter of consanguineous parents, and she had a history of recurred hypocalcemic and hypomagnesemic tetany. On physical examination, bilateral horizontal nystagmus and severe myopia were detected. Laboratory examination revealed hypomagnesemia, hypocalcemia, hypercalciuria, nephrocalcinosis, and renal stone. A clinical diagnosis of FHHNC caused possibly by claudin-19 mutation was decided with the ocular findings. DNA analysis revealed a novel homozygous missense mutation c.241C>T in the CLDN19 gene. In conclusion, in a patient with hypomagnesemia, hypercalciuria, nephrocalcinosis, and ocular findings, a diagnosis of FHHNC caused by claudin-19 mutation should be considered. This is the first study of FHHNC in Chinese population. Our findings of the novel mutation c.241C>T in exon 2 add to the list of more than 16 mutations of CLDN19 gene reported. PMID:25555744

Yuan, Tao; Pang, Qianqian; Xing, Xiaoping; Wang, Xi; Li, Yuhui; Li, Jingjun; Wu, Xueyan; Li, Mei; Wang, Ou; Jiang, Yan; Dong, Jin; Xia, Weibo

2015-04-01

391

The laminin family.  

PubMed

Laminins are large molecular weight glycoproteins constituted by the assembly of three disulfide-linked polypeptides, the ?, ? and ? chains. The human genome encodes 11 genetically distinct laminin chains. Structurally, laminin chains differ by the number, size and organization of a few constitutive domains, endowing the various members of the laminin family with common and unique important functions. In particular, laminins are indispensable building blocks for cellular networks physically bridging the intracellular and extracellular compartments and relaying signals critical for cellular behavior, and for extracellular polymers determining the architecture and the physiology of basement membranes. PMID:23263632

Aumailley, Monique

2013-01-01

392

Familial Hypercholesterolaemia  

PubMed Central

Familial hypercholesterolaemia (FH), defined as the heritable occurrence of severe hypercholesterolaemia with cholesterol deposits in tendons and premature heart disease, is caused by at least four genes in sterol and lipoprotein pathways and displays varying gene-dose effects. The genes are the low-density lipoprotein (LDL) receptor, apolipoprotein (apo) B, proprotein convertase subtilisin/kexin 9, and the autosomal recessive hypercholesterolaemia (ARH) adaptor protein. All of these disorders have in common defective clearance of LDL within a complex system of lipid and lipoprotein metabolism and regulation. Normal cellular cholesterol and lipoprotein metabolism is reviewed before describing the disorders, their metabolic derangements and their clinical effects. FH is classified as two simplified phenotypes of disease according to the severity of the metabolic derangement. The dominantly inherited heterozygous phenotype comprises defects in the LDL receptor, apoB100, and neural apoptosis regulatory cleavage protein. The homozygous phenotype is co-dominant in defects of the LDL receptor, and occurs also as the ARH of adapter protein mutations. Defective binding of apoB100 does not result in a significant gene dose effect, but enhances the severity of heterozygotes for LDL receptor mutations. The genetic diagnosis of FH has provided greater accuracy in definition and detection of disease and exposes information about migration of populations. All of these disorders pose a high risk of atherosclerosis, especially in the homozygous phenotype. Studies of influences on the phenotype and responses to treatment are also discussed in the context of the metabolic derangements. PMID:18516203

Marais, A David

2004-01-01

393

Psychoanalysis: a dysfunctional family?  

PubMed

The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve. PMID:9531859

Grosskurth, P

1998-01-01

394

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

SciTech Connect

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.

Rogers, G.R.; Lee, M.; Compton, J.G. [and others

1995-11-01

395

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

SciTech Connect

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

Levy, E. N.; Aksentijevich, I.; Pras, E. [National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD (United States)] [and others

1996-03-01

396

Family Matters: Kinship in Jane Austen [book chapter  

E-print Network

Families shape the individuals born into them in large and small ways, consciously and unconsciously; but the kinship dynamics that structure power in families are perhaps the most invisible of these forces. I doubt that ...

Perry, Ruth

2009-01-01

397

MetaMEME: Motifbased Hidden Markov Models of Protein Families  

E-print Network

, they require a relatively large training set in order to accurately characterize a given family. For families. These motif­based HMMs consist primarily of motif models generated by MEME (Multiple EM for Motif Elicitation

Bailey, Timothy L.

398

Distribution of Mycorrhizal Types among Alpine Vascular Plant Families on the Beartooth Plateau, Rocky Mountains, U.S.A., in Reference to Large-Scale Patterns in Arctic–Alpine Habitats  

Microsoft Academic Search

Mycorrhizal symbiosis is critical to plant establishment and survival, influences plant community structure and function, and could be particularly important in harsh environments such as the alpine tundra. An examination of 53 vascular plant species in 21 families from alpine areas of the Beartooth Plateau (Rocky Mountains) revealed most were mycorrhizal (68%) and four distinct types of symbioses were present.

Cathy L. Cripps; Leslie H. Eddington

2005-01-01

399

Family Anoplogastridae Gill 1893 fangtooths  

Microsoft Academic Search

The fangtooths, also commonly called ogrefishes or sabretooth fishes, are a family of two species of small but formidable-looking beryciform fishes. Head and body extremely compressed. Head large, about one- third length of body, and deep. Body deep anteriorly, sharply tapering to narrow caudal peduncle. Head sculptured-looking, with well-developed mucous cavities covered by thin skin. Eyes small. Mouth large, with

Alexander N. Kotlyar

400

Family and family therapy in Russia.  

PubMed

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

Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

2012-04-01

401

Families with Gifted Adolescents  

ERIC Educational Resources Information Center

Studies of families with gifted adolescents have revealed conflicting results. Adolescents, mothers, and fathers of 84 families with a gifted adolescent and of 95 families with a non-gifted adolescent evaluated their family system independently. Dependent variables were cohesion, democratic family style (adaptability), organisation, achievement…

Schilling, Susanne R.; Sparfeldt, Jorn; Rost, Detlef H.

2006-01-01

402

The Changing Family Structure.  

ERIC Educational Resources Information Center

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";…

Bernard van Leer Foundation Newsletter, 1993

1993-01-01

403

Family Treatment Unit.  

ERIC Educational Resources Information Center

The document describes the Family Treatment Unit, a demonstration program to provide a variety of family treatment services to status offenders (11 to 17 years old) and their families. The goals of the program are: (1) to provide family services to families of status offenders; (2) to maintain status offenders in their natural homes by…

Sawicki, Donna

404

Boston University Family Medicine  

E-print Network

Boston University Family Medicine Global Health CollaborativeFamily Medicine As part of the Department of Family Medicine at Boston University, the Collaborative is committed to introducing and improving Family Medicine programs around the world. Family Medicine is a holistic specialty that attends

Spence, Harlan Ernest

405

Family Reading Night  

ERIC Educational Resources Information Center

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

Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

2007-01-01

406

The truncated nuclear family  

Microsoft Academic Search

The truncated nuclear family is defined: it is the garden-variety family “pathology” found. The critical role of polarized continuity and discontinuity values in producing the truncated nuclear family is discussed. There is a brief review of factors in American society which, over the decades since the Second World War, have evolved the nuclear family as a dominant family unit, and

Gerald H. Zuk

1985-01-01

407

Bounding CKM Mixing with a Fourth Family  

E-print Network

CKM mixing between third family quarks and a possible fourth family is constrained by global fits to the precision electroweak data. The dominant constraint is from nondecoupling oblique corrections rather than the Zbb vertex correction used in previous analyses. The possibility of large mixing suggested by some recent analyses of FCNC processes is excluded, but 3-4 mixing of the same order as the Cabbibo mixing of the first two families is allowed.

Michael S. Chanowitz

2009-04-27

408

Collisional Formation and Modeling of Asteroid Families  

E-print Network

In the last decade, thanks to the development of sophisticated numerical codes, major breakthroughs have been achieved in our understanding of the formation of asteroid families by catastrophic disruption of large parent bodies. In this review, we describe numerical simulations of asteroid collisions that reproduced the main properties of families, accounting for both the fragmentation of an asteroid at the time of impact and the subsequent gravitational interactions of the generated fragments. The simulations demonstrate that the catastrophic disruption of bodies larger than a few hundred meters in diameter leads to the formation of large aggregates due to gravitational reaccumulation of smaller fragments, which helps explain the presence of large members within asteroid families. Thus, for the first time, numerical simulations successfully reproduced the sizes and ejection velocities of members of representative families. Moreover, the simulations provide constraints on the family dynamical histories and on...

Michel, Patrick; Durda, Daniel D; Jutzi, Martin; Asphaug, Erik

2015-01-01

409

The expanding family Marseilleviridae.  

PubMed

The family Marseilleviridae encompasses giant viruses that replicate in free-living Acanthamoeba amoebae. Since the discovery of the founding member Marseillevirus in 2007, 7 new marseilleviruses have been observed, including 3 from environmental freshwater, one from a dipteran, and two from symptom-free humans. Marseilleviruses have ?250-nm-large icosahedral capsids and 346-386-kb-long mosaic genomes that encode 444-497 predicted proteins. They share a small set of core genes with Mimivirus and other large and giant DNA viruses that compose a monophyletic group, first described in 2001. Comparative genomics analyses indicate that the family Marseilleviridae currently includes three lineages and a pan-genome composed of ?600 genes. Antibodies against marseilleviruses and viral DNA have been observed in a significant proportion of asymptomatic individuals and in the blood and lymph nodes of a child with adenitis; these observations suggest that these giant viruses may be blood borne and question if they may be pathogenic in humans. PMID:25104553

Aherfi, Sarah; La Scola, Bernard; Pagnier, Isabelle; Raoult, Didier; Colson, Philippe

2014-10-01

410

Family boundary characteristics, work-family conflict and life satisfaction: A moderated mediation model.  

PubMed

Although work-family border and boundary theory suggest individuals' boundary characteristics influence their work-family relationship, it is largely unknown how boundary flexibility and permeability mutually influence work-family conflict and subsequent employee outcomes. Moreover, the existing work-family conflict research has been mainly conducted in the United States and other Western countries. To address these gaps in the work-family literature, the present study examines a moderated mediation model regarding how family boundary characteristics may influence individuals' work-family conflict and life satisfaction with a sample of 278 Chinese full-time employees. Results showed that employees' family flexibility negatively related to their perceived work interference with family (WIF) and family interference with work (FIW), and both these two relationships were augmented by individuals' family permeability. In addition, WIF mediated the relationship between family flexibility and life satisfaction; the indirect effect of family flexibility on life satisfaction via WIF was stronger for individuals with higher family permeability. The theoretical and managerial implications of these findings are discussed. PMID:25331584

Qiu, Lin; Fan, Jinyan

2014-10-21

411

Family members' influence on family meal vegetable choices  

PubMed Central

Objective Characterize the process of family vegetable selection (especially cruciferous, deep orange, and dark green leafy vegetables); demonstrate the usefulness of Exchange Theory (how family norms and past experiences interact with rewards and costs) for interpreting the data. Design Eight focus groups, two with each segment (men/women vegetable-likers/dislikers based on a screening form). Participants completed a vegetable intake form. Setting Rural Appalachian Pennsylvania. Participants 61 low-income, married/cohabiting men (n=28) and women (n=33). Analysis Thematic analysis within Exchange Theory framework for qualitative data. Descriptive analysis, t-tests and chi-square tests for quantitative data. Results Exchange Theory proved useful for understanding that regardless of sex or vegetable-liker/disliker status, meal preparers see more costs than rewards to serving vegetables. Past experience plus expectations of food preparer role and of deference to family member preferences supported a family norm of serving only vegetables acceptable to everyone. Emphasized vegetables are largely ignored due to unfamiliarity; family norms prevented experimentation and learning through exposure. Conclusions and Implications Interventions to increase vegetable consumption of this audience could 1) alter family norms about vegetables served, 2) change perceptions of past experiences, 3) reduce social and personal costs of serving vegetables and 4) increase tangible and social rewards of serving vegetables. PMID:20452288

Wenrich, Tionni R.; Brown, J. Lynne; Miller-Day, Michelle; Kelley, Kevin J.; Lengerich, Eugene J.

2010-01-01

412

Family Research and Family Therapy: A Reunion?  

ERIC Educational Resources Information Center

Identifies several of the most important forms of recent and current family research and family therapy that are important to clinicians. Suggests that the reunion of clinical and research interests signifies a new growth of the family therapy field. (Author/JAC)

Wynne, Lyman C.

1983-01-01

413

Family Capital: Implications for Interventions with Families  

ERIC Educational Resources Information Center

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…

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

2011-01-01

414

Importance of Family Routines  

MedlinePLUS

... Pediatric First Aid for Caregivers and Teachers (PedFACTs) Teaching Package First Aid for Families (PedFACTs) Allergies and Asthma Family Life Health Management - Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types ...

415

Family Reunion Health Guide  

MedlinePLUS

... HEALTH GUIDE 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. ...

416

Graduate School INTERNATIONAL FAMILY  

E-print Network

Graduate School Graduate School INTERNATIONAL FAMILY AND COMMUNITY STUDIES Doctor of Philosophy Certificate the doctoral program in International Family and community Studies educates professionals to generate, diffuse, and apply knowledge needed to strengthen communities' capacity for family support

Stuart, Steven J.

417

Choosing a Family Doctor  

MedlinePLUS

... do? Family doctors take care of the physical, mental and emotional health of both their patients and their patients' families. They know your family's health history and how it can affect you. They are ...

418

Media Time Family Pledge  

MedlinePLUS

... Media Time Family Pledge Family Life Listen Media Time Family Pledge Article Body At the beginning and ... them. Kids learn best with small lessons over time as opposed to one big lecture or sit- ...

419

About Familial Pulmonary Fibrosis  

MedlinePLUS

About Familial Pulmonary Fibrosis An estimated 10-15 percent of patients with idiopathic pulmonary fibrosis (IPF) have a form of the pulmonary fibrosis that runs in families. This is called Familial ...

420

Characterization of familial breast cancer in Saudi Arabia  

PubMed Central

Background The contribution of genetic factors to the development of breast cancer in the admixed and consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset. The current protocols of continuous clinical follow-up of relatives of such patients are costly and cause a burden on the usually over-stretched medical resources. Discovering the significant contribution of BRCA1/2 mutations to breast cancer susceptibility allowed for the design of genetic tests that allows the medical practitioner to focus the care for those who need it most. However, BRCA1/2 mutations do not account for all breast cancer susceptibility genes and there are other genetic factors, known and unknown that may play a role in the development of such disease. The advent of whole-exome sequencing is offering a unique opportunity to identify the breast cancer susceptibility genes in each family of sufferers. The polymorphisms/mutations identified will then allow for personalizing the genetic screening tests accordingly. To this end, we have performed whole-exome sequencing of seven breast cancer patients with positive family history of the disease using the Agilent SureSelect™ Whole-Exome Enrichment kit and sequencing on the SOLiD™ platform. Results We have identified several coding single nucleotide variations that were either novel or rare affecting genes controlling DNA repair in the BRCA1/2 pathway. Conclusion The disruption of DNA repair pathways is very likely to contribute to breast cancer susceptibility in the Saudi population.

2015-01-01

421

[Integration in family planning programs].  

PubMed

The question of whether family planning programs should be integrated with other activities or limited strictly to contraception has been debated for years without achievement of consensus. Profamilia, the Colombian family planning organization, has been a firm advocate of a vertical program without other activities. A large body of economic and demographic data and evaluations of numerous programs in numerous places support the Profamilia position that both economic development and family planning programs are important in achieving demographic objectives, but if only 1 is possible in a given country, a good family planning program gives better results. Profamilia, a private, nonprofit organization, is responsible for 2/3 of the contraception practiced in Colombia. Profamilia's success appears to demonstrate that an effective program, even in a country no more promising otherwise than any of its neighbors, can achieve excellent results. For government-run programs, it may be politically impossible to avoid an integrated family planning program; the public is likely to question the emphasis on family planning if other urgent health needs go unattended. But even government-run programs may create separate structures with separate funding and personnel for specific problems such as malaria control, suggesting recognition of their greater efficiency. A nongovernmental organization such as Profamilia, faced with a continuing struggle for funding, must concentrate its resources on fulfilling its mission of allowing couples to decide freely on the timing and extent of their reproduction. Vertical programs, tolerant if not enthusiastic governments, and abundant demand are the 3 factors that have led to high rates of contraceptive usage in some countries; sthe contraceptive prevalence rate is 60% in Colombia. A number of studies in the late 1970s and early 1980s have shown that funds directed to family planning have a far greater demographic impact than do equal amounts directed to rural female education, nutrition, or control of infant mortality. Verticality in a family planning program should be understood to include all activities that attract potential family planning acceptors, as well as all services which generate funds that can be channeled to family planning programs and that contribute to program efficiency. Pregnancy tests, Pap smears, gynecological or urological consultations, social marketing, antiparasite campaigns, and treatments of infertility, sexually transmitted diseases, or sexual dysfunctions are all appropriate components of a vertical family planning program. True and unacceptable integration views contraception as a remote and secondary goal, while the type of "false" integration described above views family planning as its epicenter and does everything possible to promote and facilitate contraception. PMID:12268899

Trias, M

1987-01-01

422

Changing Family, Changing Education  

Microsoft Academic Search

\\u000a Sociologists of education increasingly have recognized the crucial role that families assume in children’s educational development.\\u000a Meanwhile, sociologists have identified major changes in family structure and contemporary family life—among these, increases\\u000a in the number of single-parent and step-parent families, families with older parents, and same-sex families, adoptive families,\\u000a and multiracial families. These changes have compelled sociologists of education to redirect

Laura Hamilton; Regina Werum; Lala Carr Steelman; Brian Powell

423

Incidence of Wife Abuse in Incestuous Families.  

ERIC Educational Resources Information Center

Investigates a largely uncharted dynamic in the literature--the incidence of wife abuse among incestuous families--and suggests that professional caregivers reevaluate conventional treatment modalities that are based on certain assumptions regarding the mother's role in incest. (Author)

Truesdell, Donna L.; And Others

1986-01-01

424

Family Court counselling with separating families.  

PubMed

Family Court counsellors, attached to the Family Court, see married couples who are separating, particularly those already involved, or likely to be, in Court disputes concerning their children. Children seen by the counsellors are from families in crises, and are usually detrimentally affected by family separation, and more so by any accompanying conflict. The impact on them depends on their developmental stage and position in the family system, and may be manifested in aggressive behaviour, general anxiety, psychosomatic symptoms, or manipulation and 'acting out'. The examination of the whole family system is essential to defuse the situation and thereby move the focus from the children; the close cooperation of all professionals working with the family is necessary to achieve this. PMID:7225212

Scambler, D

1980-08-01

425

A novel seven-base deletion of the CTSC gene identified in a Hungarian family with Papillon-Lefèvre syndrome.  

PubMed

Papillon-Lefévre syndrome (PLS; OMIM 245000) is a rare autosomal recessive condition characterized by symmetrical palmoplantar hyperkeratosis and periodontal inflammation, causing loss of both the deciduous and permanent teeth. PLS develops due to mutations in the cathepsin C gene, CTSC. Recently we have identified a Hungarian PLS family with two affected siblings. Direct sequencing of the coding regions of the CTSC gene revealed a novel seven-base deletion leading to frameshift and early stop codon in the fourth exon of the CTSC gene (c.681delCATACAT, p.T188fsX199). The affected family members carried the mutation in homozygous form, while the clinically unaffected family members carried the mutation in heterozygous form. The unrelated controls carried only the wild type sequence. In this paper we report a novel homozygous deletion of seven bases on the CTSC gene leading to the development of PLS. Since consanguineous marriage was unknown in the investigated family, the presence of the homozygous seven-base deletion of the CTSC gene may suggest that the parents are close relatives. PMID:23397598

Farkas, Katalin; Paschali, Ekaterine; Papp, Ferenc; Vályi, Péter; Széll, Márta; Kemény, Lajos; Nagy, Nikoletta; Csoma, Zsanett

2013-07-01

426

Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family  

PubMed Central

Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in the ECM1 gene located on chromosome 1q21. The aim of the study was to investigate the molecular genetic defect underlying lipoid proteinosis in a consanguineous Pakistani family. Methods Genotyping of seven members of the family was performed by amplifying microsatellite markers, tightly linked to the ECM1 gene. To screen for mutations in the ECM1 gene, all of its exons and splice junctions were PCR amplified from genomic DNA and analyzed by SSCP and sequenced directly in an ABI 3130 genetic analyzer. Results The results revealed linkage of the LP family to the ECM1 locus. Sequence analysis of the coding exons and splice junctions of the ECM1 gene revealed a novel homozygous mutation (c.616C > T) in exon 6, predicted to replace glutamine with stop codon (p.Q206X) at amino acid position 206. Conclusions The finding of a novel mutation in Pakistani family extends the body of evidence that supports the importance of ECM1 gene for the development of lipoid proteinosis. PMID:21791056

2011-01-01

427

Building a family: unplanned events.  

PubMed

Couples in developed societies are often unsuccessful in achieving precise family building goals despite the widespread use of birth control. Unplanned events that frustrate reproductive intentions to varying degrees include contraceptive failure, sterility, miscarriage, prolonged conception delay, undesired sex combination of offspring, divorce, and the death of a spouse or a child. This paper reviews the probability of the occurrence of these events using US data. It is concluded that the large majority of newlyweds will experience at least one unplanned event during the family building phase of the life cycle. PMID:6701951

Bongaarts, J

1984-01-01

428

Changing Family Forms.  

ERIC Educational Resources Information Center

Explores the definition of family. Considers three facets of the contemporary family measured by U.S. Census statistics: (1) marriage and divorce trends; (2) declining fertility; and (3) the rise in single-headed families. Addresses the societal changes (economic, cultural, legal, and technological) that have influenced the changes in family

Seibert, M. Therese; Willetts, Marion C.

2000-01-01

429

Families in Transition .  

ERIC Educational Resources Information Center

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…

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

1984-01-01

430

THE FAMILY FLAVIVIRIDAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The family Flaviviridae, commonly referred to as the flavivirus family, contains viruses important to both human and veterinary medicine. The term flavivirus can be confusing because it is used both to refer to the family and one of the three genera within that family. The proper name of the viral...

431

Black Families. Third Edition.  

ERIC Educational Resources Information Center

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…

McAdoo, Harriette Pipes, Ed.

432

Familial malignant retroperitoneal paraganglioma.  

PubMed Central

Paragangliomas are neuroendocrine tumours and those occurring in the head and neck have well recognized familial association. Retroperitoneal paragangliomas are uncommon and we present two cases of familial malignant retroperitoneal paraganglioma. Review of the literature revealed marked differences in the incidence and malignant potential of familial and non-familial paraganglioma. In contrast to the cases reported here, familial tumours are generally benign, though they may occur at multiple sites. Familial and non-familial paragangliomas may indeed be different disease entities. Images Figure 1 Figure 2 Figure 3 PMID:2559401

Sebastian, J. P.; Williams, S. E.; Wells, M.; Peake, M. D.

1989-01-01

433

Familial Malignant Melanoma - Overview  

PubMed Central

Approximately 3-15% of all malignant melanomas (MM) are familial cases. MM is a highly heterogeneous tumour type from a genetic perspective. Pedigrees with disease confined to a single generation of siblings or MM occurring among second- or third-degree relatives suggest multifactorial polygenic inheritance. However, not infrequently, within large families aggregations of MM are consistent with autosomal dominant inheritance, suggesting a hereditary syndrome caused by germline alterations of a single gene. Several different genes are involved in the development of MM. However, even when taken together they are responsible for less than 20% of all MM cases. It is thus necessary to perform association studies focused on genetic markers that could be used in identifying patients with a high risk of MM. Evaluation of aggregations of MM and other malignancies, like breast cancer, could be essential in identifying relatives of MM probands being at high risk of developing malignancies other than MM. The ultimate goal is to apply in these cases prevention recommendations and surveillance protocols to reduce the disease risk. PMID:20233466

2004-01-01

434

FamilySearch  

NSDL National Science Digital Library

Although still in beta phase, this impressive new genealogical resource from the Church of Jesus Christ of Latter-Day Saints (the Mormons) has immediately received the attention and praise of genealogical researchers. The providers have not publicly stated whether the site will offer access to the entirety of their 2 billion name genealogical record repository, but it already contains over 300 million names in two indexes, searchable by ancestor name. Users may also search a host of other genealogy Websites and the site's own SourceGuide of research outlines by keyword. In addition, the site offers a large collection of browseable and searchable categories of genealogical research sites, such as Census and Lists, Land and Property, Migration, Military, Vital Records, and others. Registered users can collaborate with others working on similar projects, add Websites, and have their research preserved in The Pedigree Resource File. While the Internet already holds a multitude of family research sites, when it is complete, FamilySearch will almost certainly be regarded as the first and most comprehensive place to begin a search for one's ancestors.

1999-01-01

435

Family Allowances and Fertility: Socioeconomic Differences  

PubMed Central

This article explores socioeconomic differences in the effect of family allowances on fertility. Although several studies have examined the relationship between cash benefits and fertility, few studies have addressed the possible differential effects of cash benefits on families of different income or education levels. I reconstructed the birth histories of women in the past two Israeli censuses of 1983 and 1995 to study socioeconomic differences in the effect of family allowances up to the seventh parity. The results indicate that family allowances have a significant effect at every parity. Using female education as an indicator of socioeconomic status, I find that socioeconomic status is a significant modifier of the effect of family allowances. Family allowances seem to have a relatively large impact on more-educated women. PMID:19771939

SCHELLEKENS, JONA

2009-01-01

436

The utility of exome sequencing for genetic diagnosis in a familial microcephaly epilepsy syndrome  

PubMed Central

Background Despite remarkable advances in genetic testing, many adults with syndromic epilepsy remain without a molecular diagnosis. The challenge in providing genetic testing for this patient population lies in the extensive genetic heterogeneity associated with epilepsy. Even for the subset of epilepsy patients that present with a defining feature, such as microcephaly, the number of possible genes that would require interrogation by Sanger sequencing is extensive and often prohibitively expensive. Case presentation We report a family of French Canadian descent with four adult children affected with severe intellectual disability, epilepsy and microcephaly born to consanguineous parents and evaluated by the Genetics Service to provide informed genetic counseling to unaffected family members regarding possible recurrence risks. We used whole-exome sequencing (WES) of DNA from one affected sibling as a first-line diagnostic tool and compared the prioritization of variants using two strategies: 1) focusing on genes with homozygous variants; and, 2) focusing on genes associated with microcephaly. Both approaches prioritized the same homozygous novel frameshift mutation (p.Arg608Serfs*26) in WDR62, a gene known to cause autosomal recessive primary microcephaly. Sanger sequencing confirmed the presence of the homozygous mutation in the other three affected siblings. Conclusions WES and subsequent filtering of the rare variants in a single affected family member led to the rapid and cost-effective identification of a novel homozygous frameshift mutation in WDR62, thereby explaining the severe neurodevelopmental disorder in this family and facilitating genetic counseling. Our findings support WES as an effective first-line diagnostic tool in families presenting with rare genetically heterogeneous neurological disorders. PMID:24479948

2014-01-01

437

Familial hypocalciuric hypercalcemia associated with mutation in the human Ca{sup 2+}-sensing receptor gene  

SciTech Connect

Familial hypocalciuric hypercalcemia (FHH) is generally characterized by lifelong hypercalcemia without hypercalciuria and is inherited in an autosomal dominant manner. Affected individuals show abnormal parathyroid and renal responses to changes in the extracellular calcium concentration. A Japanese FHH family was screened for mutations in the Ca{sup 2+} -sensing receptor gene by the polymerase chain reaction and single strand conformation polymorphism. The proband with hypercalcemia showed an abnormal pattern in exon 1 of the gene, whereas her two sisters with normocalcemia showed a normal pattern. The consanguineous parents with borderline serum calcium concentrations showed both patterns. Nucleotide sequence analysis identified a G{yields}C point mutation at nucleotide 118 that resulted in the conversion of the normal codon for proline into a codon for alanine at amino acid 40 (numbered according to the bovine complementary DNA). The proband was homozygous for the mutation, and the parents were heterozygous. These results imply that this mutation in the human Ca{sup 2+}-sensing receptor gene causes FHH and that the dosage of the gene defect determines disease phenotype. 33 refs., 4 figs., 1 tab.

Aida, Kaoru; Koishi, Sawako; Inoue, Masaharu [Univ. of Yamanashi Medical School, Yamanashi (Japan)] [and others] [Univ. of Yamanashi Medical School, Yamanashi (Japan); and others

1995-09-01

438

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

SciTech Connect

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.

Thomas, P.M.; Cote, G.J. [Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Hallman, D.M. [Univ. of Texas Health Science Center, Houston, TX (United States); Mathew, P.M. [Dhahran Health Center (Saudi Arabia)

1995-02-01

439

Ibsen's truth, family secrets, and family therapy.  

PubMed

In certain Ibsen plays a character (would-be family therapist) enters during a crisis revolving around family secrets. Taking two such plays as models, this paper examines family processes and clinical issues surrounding secrets and myths. In Ghosts, Ibsen demonstrates the tragic foreclosure visited upon the Alvings' lives by a generation of secrecy. For contrast, in The Wild Duck the would-be reformer Gregers brings out the truth, to expose and correct consequences of his father's past machinations. The biographical roots of Ibsen's obsession with truth and illusion are explored. Lastly, the notion that Ibsen and early family therapist were reformers is viewed in historical perspective. PMID:6628642

Grolnick, L

1983-09-01

440

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

PubMed

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

Peters, Timothy J; Willis, Clive

2013-09-01

441

Linkage Analysis in Families with Joubert Syndrome Plus Oculo-Renal Involvement Identifies the CORS2 Locus on Chromosome 11p12-q13.3  

PubMed Central

Joubert syndrome (JS) is an autosomal recessive developmental brain condition characterized by hypoplasia/dysplasia of the cerebellar vermis and by ataxia, hypotonia, oculomotor apraxia, and neonatal breathing dysregulation. A form of JS that includes retinal dysplasia and cystic dysplastic kidneys has been differentiated from other forms of JS, called either “JS type B” or “cerebello-oculo-renal syndrome” (CORS), but the genetic basis of this condition is unknown. Here, we describe three consanguineous families that display CORS. Linkage analysis defines a novel locus on chromosome 11p12-q13.3, with a maximum two-point LOD score of Z=5.2 at the marker D11S1915. Therefore, the cerebello-oculo-renal form of JS is a distinct genetic entity from the Joubert syndrome 1 (JBTS1) locus described elsewhere, in which there is minimal involvement of retina or kidney. We suggest the term “CORS2” for this new locus. PMID:12917796

Keeler, Lesley C.; Marsh, Sarah E.; Leeflang, Esther P.; Woods, Christopher G.; Sztriha, László; Al-Gazali, Lihadh; Gururaj, Aithala; Gleeson, Joseph G.

2003-01-01

442

Military Recognition of Family Concerns: Revolutionary War To 1993  

Microsoft Academic Search

This article explores the evolution of military recognition of family concerns from the Revolutionary War to the present, culminating in the development of a federally funded, worldwide network of military Family Centers. Demographic change played a large role in the military capacity to maintain itself as a dramatic influx of family members during the 1960s and the need to maintain

Sondra Albano

1994-01-01

443

Stewardship vs. Stagnation: An Empirical Comparison of Small Family and Non-Family Businesses &ast  

Microsoft Academic Search

abstract? Two major perspectives can be construed in the literature concerning the nature of family owned businesses (FOBs). The first implies that these enterprises have unique characteristics of stewardship. FOB owners are said to care deeply about the long-term prospe