Carrier detection and prenatal diagnosis in 98 families of haemophilia A by linkage analysis and direct detection of mutations

“…Finally, our findings have also implications for indirect HEMA carrier detection with X‐STR. Among researchers in the field, there is the notion that the strength of GD between neighbouring locus pairs considerably limits the informativeness of the typing markers [46,47]. However, it is important to note that typing with X‐STR remains a powerful method in segregation analysis of genetic traits, and what is crucial in segregation analysis is the cumulative informativeness (i.e.…”

Section: Discussionmentioning

confidence: 99%

Interlocus non‐random association of multiallelic polymorphisms spanning the coagulation factor VIII gene on human chromosome distalmost Xq28

Medina‐Acosta

2010

Haemophilia

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The most common severe hereditary bleeding disorder phenotype in humans, the coagulation factor VIII (F8) deficiency haemophilia A (HEMA), maps on Xq28 band, a region that comprises 11.7% of genes and 14.2% of phenotypes on X chromosome. Information about the distribution and extent of gametic disequilibrium (GD) covering the F8 gene is scarce, despite its relevance for linkage and association studies. The aim of this study was to determine the patterns, by frequency and strength, of non-random multiallelic interallelic associations between two-locus combinations of seven microsatellite loci (REN90833, F8Int25.2, F8Int22, F8Int13.2, HEMA154311.3, TMLHEInt5 and HEMA154507.3, in that physical order) spanning 0.813 Mb on distalmost Xq28. We measured sign-based interallelic D' coefficients in 106 men and in 100 women drawn from a single unrelated Brazilian population. Significance and patterns of GD using haploid and phased diploid sample probabilities were close to conformity. Only 9.18% of the variance of D' could be accounted for by changes in length, indicating that GD is not a monotonically decreasing function of length. We defined two regions of overlapping long-range GD extending 698 735 base pairs (bp) (REN90833/TMLHEInt5 block) and 689 900 bp (F8Int13.2/HEMA154507.3 block) The extent of GD overlap is 575 637 bp (F8Int13.2/TMLHEInt5 interstice). Extended haplotype homozygosity analysis centred at the F8 intronic loci revealed that the most frequent core haplotypes decay the least in the flanking GD. The F8 intronic loci attend distinct non-random association forces; F8Int13.2 serves at maintenance of the long-range overlapping pattern of GD, whereas F8Int25.2 and F8Int22 serve at lessening it in force or effect.

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Molecular Biology and Medicine

Bello¹,

Schwinn²

1996

Anesthesiology

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Carrier detection and prenatal diagnosis in 98 families of haemophilia A by linkage analysis and direct detection of mutations

Cited by 4 publications

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Mechanisms by which von Willebrand Disease Mutations Destabilize the A2 Domain*

Mechanisms by which von Willebrand Disease Mutations Destabilize the A2 Domain*

Interlocus non‐random association of multiallelic polymorphisms spanning the coagulation factor VIII gene on human chromosome distalmost Xq28

Molecular Biology and Medicine

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