Fróðskaparrit - 01.01.1998, Qupperneq 7

Fróðskaparrit - 01.01.1998, Qupperneq 7
ARVAEGINLEIKAKANNINGAR í FØROYUM 13 Table 2. The probability of segment sharing by chance with two neighbouring markers not linked to the disease in proportions out of 16 chromosomes. P(com) is the probability when the most common allele at each locus makes the pair, p(IBS) are the probabilities summedfor all possible pairsfor the dijferent haplotypes. Talva 2. Víst verður hvussu sannlíkt tað er, at eitt felags petti við tveimum grannamørkum verður arvað, mett sum tøl í mun til 16 kromosom. P(com) er hvussu sannlíkt tað er, tá títtasti allelur gongur sum par, p(IBS) er hvussu sannlíkt tað er, tá allir møguleikar eru við fyri ymsar haplotypir. p(com) p(IBS) any 3 out of 16 0.23778 0.70104 any 4 out of 16 0.14720 0.24294 any 5 out of 16 0.06729 0.08386 any 6 out of 16 0.02350 0.02584 any 7 out of 16 0.00639 0.00666 any 8 out of 16 0.00137 0.00139 share a haplotype which is by chance iden- tical by descent can be calculated from for- mulas derived by Houwen et al. (1994) (Table 2). A s shown even as little as 2 out of 8 individuals sharing a haplotype identi- cal by descent is a rare event which even a genome wide scan only occurs a few times for persons related six or more generations ago. When considering alleles at two neigh- bouring markers and which alleles are in linkeage equilibrium the probability of seg- mentsharing just by chance is dependent on the marker allele frequencies. For two neighbouring markers with 6 alleles each with frequencies of 0.4, 0.2, 0.15, 0.1 and 0.05 these probabilities are shown in Table 2. It is crucial to choose which amount of sharing that is needed before a chromoso- mal area is considered iteresting. If the treshhold is set too high the disease gene re- gion may be missing and if the treshhold is set too low to many false positive regions will have be tested with additional markers. Genetic analyses DNA was prepared from whole blood, us- ing a standard triton lysis, nuclear lysis pro- tocol with sodium chloride/isopropanol precipitation. DNA amplification was em- ployed using a Perkin-Elmer thermocycler with optimised reaction conditions for each primer set and analysed on the ABI Prism 310 Genetic Analyzer. As part of an ongoing genome wide scan twelve markers were tested on chromo- somes 16 and 18 (Table 3). Results Preliminary results are shown in Table 3. On chromosome 16 at least 10 alleles were shared for the most distal marker tested D16S2622. Evidence of segment sharing did not recieve support from the marker proximal for D16S2622. On chromosome 18 for marker D18S877 11 out of 16 alleles were shared while for marker D18S541 13 out of 16 alleles were shared. This did receive some support from neighbouring markers. Discussion As the Faroese population descended from Scandinavian and British ancestors, and probably are founded from much fewer people than Iceland, disease genes found in this population are of great potential rele- vance.
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