Yes / Consanguineous marriage is a controversial topic in many Western societies, with attention mainly focused on the health of immigrant communities from Asia and Africa. In the UK consanguinity is especially prevalent in the Pakistani community which now numbers over 1.1 million. Less attention has been paid to the influence of hereditary population stratification within Pakistani communities. In particular, biraderi (literally brotherhood) membership which denotes male lineages that largely govern marriage partner choice and hence the transmission of disease genes. The various roles played by biraderi and their relationship to other socio-occupational and kinship terms, such as caste, quom and zat, are often overlooked in health-based studies. The interchangeable use of these different kinship terms without rigorous definition can create identity uncertainty and hinders inter-study comparisons. Where feasible, standardization of terminology would be both desirable and beneficial, with biraderi the preferred default term to identify specific social and genetic relationships within the Pakistani diaspora.

The study of human relatedness has long interested the population geneticist. One technique for the estimation of population relatedness is the use of isonymy analysis. The isonymy inbreeding coefficient is analogous to Wright's inbreeding coefficient F. Isonomy analysis can yield comparable results to population studies done by other means such as pedigree analysis, serological studies, and anthropometric analysis. The data used for this study was obtained from marriage records and telephone directories. Same last name marriages were observed for legitimacy and recorded when verified. A pool of last names were drawn from the marriage records. This list was used to compare and tally like names found in telephone directories for corresponding years and localities.

Thesis (J.C.L.)--Catholic University of America, 1991. / Includes bibliographical references (leaves 50-54).

Mémoire (M.Sc.)-- Université du Québec à Chicoutimi, 1992. / Ce mémoire a été réalisé à l'UQAC dans le cadre du programme de maîtrise en médecine expérimentale (génétique) extensionné de l'U. Laval à l'UQAC. CaQCU Bibliogr.: f. 98-103. Document électronique également accessible en format PDF. CaQCU

Thèse (M.E.S.R.). / En tête du titre: Université du Québec à Chicoutimi, mémoire présenté à l'Université du Québec à Chicoutimi comme exigence partielle de la maîtrise en études régionales. CaQCU Document électronique également accessible en format PDF. CaQCU

Thesis (J.C.L.)--Catholic University of America, 1991. / This is an electronic reproduction of TREN, #029-0217. Includes bibliographical references (leaves 50-54).

La maladie de Charcot-Marie-Tooth représente un groupe hétérogène de maladies tant sur le plan clinique que sur le plan génétique. A ce jour, on dénombre 60 gènes décrits dans la maladie de CMT. En Tunisie, le fort taux de consanguinité est un facteur majeur de l'apparition des maladies génétiques en particulier des formes autosomiques récessives parmi lesquelles, on trouve la maladie de Charcot-Marie-Tooth. Deux formes de CMT ont été identifiées dans cette population, il s'agit de la forme CMT4A et la forme de CMT4B2. Mes travaux de thèse ont consisté à identifier de nouveaux gènes chez des familles tunisiennes consanguines atteintes de CMT en utilisant différentes approches de criblages. J'ai poursuivi aussi des travaux de localisation réalisées chez deux familles libanaises consanguines et pour lesquelles les analyses n'ont pas permis d'identifier une région homozygote par descendance. Nous avons pu caractériser les formes CMT4H, CMT4C et CMT1A dans la population tunisienne. Nous avons identifié une nouvelle mutation dans le gène FGD4 impliquée dans la forme CMT4H. Nous avons pu caractériser la forme CMT4C par l'identification d'une nouvelle mutation dans le gène SH3TC2. En utilisant la technique d'hybridation génomique comparative sur des puces CGH , le criblage nous a permis de mettre en évidence la forme dominante CMT1A chez des patients tunisiens. / My research is entitled "Molecular analysis of consanguineous families Tunisian and Lebanese with clinical signs of Charcot-Marie-Tooth disease". The objectives of the PhD research were to identify and localize the genes implicated in these clinic forms of CMT and to elucidate the functional impact of mutations and the associated physiopathology mechanisms. For this purpose several technologies were used such as Fluorescent Direct Sequencing of known genes published in CMT disease. We have identified two novel mutations in patients from consanguineous Tunisian families: the first mutation (c.514_514insG; p.Ala172Glyfs*27) was detected in FGD4 by Fluorescent direct sequencing. Skin and nerve biopsy structure of these patients were studied under a microscope. Furthermore, the expression profile of FRABIN was studied by western blot. The cellular localization of this protein is under further examinations with the use of immunofluorescent. The second mutation (c.2968delC; p.Leu990Trpfs*24) was identified using High throughput sequencing in the SH3TC2 gene, The duplication of CMT1A in patients from Tunisia was demonstrated by Array CGH technique. The identified mutations will be subjected to functional studies to determine their impact on protein and to investigate the pathophysiology of this disease. Detail data analysis is currently underway for these projects using High throughput sequencing and other methods as appropriate in both Tunisian and Lebanese families.

Interpretation and simulation of the large-scale genomics data are very challenging, and currently, many web tools have been developed to analyze genomic variation which supports automated visualization of a variety of high throughput genomics data. We have developed VSIM an automated and easy to use web application for interpretation and visualization of a variety of genomics data, it identifies the candidate diseases variants by referencing to four databases Clinvar, GWAS, DIDA, and PharmGKB, and predicted the pathogenic variants. Moreover, it investigates the attitude towards premarital genetic screening by simulating a population of children and analyze the diseases they might be carrying, based on the genetic factors of their parents taking into consideration the recombination hotspots. VSIM supports output formats based on Ideograms that are easy to interpret and understand, which makes it a biologist-friendly powerful tool for data visualization, and interpretation of personal genomic data. Our results show that VSIM can efficiently identify the causative variants by referencing well-known databases for variants in whole genomes associated with different kind of diseases. Moreover, it can be used for premarital genetic screening by simulating a population of offspring and analyze the disorders they might be carrying. The output format provides a better understanding of such large genomics data. VSIM thus helps biologists and marriage counsellor to visualize a variety of genomic variants associated with diseases seamlessly.

No description available.

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