Polymorphism Research Laboratory, Department of Psychiatry, The University of California, San Diego, La Jolla, California 92093-0603, USA.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S35. doi: 10.1186/1471-2156-6-S1-S35.
We have developed a simulation-based approach to the analysis of shared homozygous chromosomal segments and have applied it to data on allele sharing among alcoholics in a single Collaborative Study on the Genetics of Alcoholism pedigree. Our assessment of sharing involved the use of a single-nucleotide polymorphism (SNP) marker map provided by Affymetrix.
All 11 affected individuals in the selected pedigree shared 2 copies of an allele at 4 adjacent SNPs in a region on chromosome 5. Via simulation, we determined that the probability that such sharing is caused by mere chance is less than 0.0000001. After correcting for undocumented inbreeding, this probability rose to 0.0016. The probability that the shared segment emanates from a single ancestor and is unrelated to the affection status is less than 0.0000001 in the corrected pedigree. Haplotype association analysis and a search for a protective locus using unaffected individuals yielded no significant results.
Homozygosity mapping results on chromosome 5 provide suggestive evidence of the region's role as one that may harbor a genetic determinant of alcoholism. Furthermore, the probabilities of chance homozygous allele sharing for the original and for the inbreeding-corrected pedigree provide insight into the impact that inbreeding can have on such calculations.
我们开发了一种基于模拟的方法来分析共享纯合染色体片段，并将其应用于单个酒精中毒遗传学协作研究谱系中酒精中毒患者等位基因共享的数据。我们的共享评估涉及使用 Affymetrix 提供的单核苷酸多态性（SNP）标记图谱。
所选谱系中的所有 11 名受影响个体在染色体 5 上的一个区域中共享 4 个相邻 SNP 的等位基因的 2 个拷贝。通过模拟，我们确定这种共享是偶然发生的概率小于 0.0000001。在纠正未记录的近亲繁殖后，这个概率上升到 0.0016。在纠正后的谱系中，共享片段源自单个祖先且与情感状态无关的概率小于 0.0000001。单体型关联分析和使用未受影响个体寻找保护基因座均未产生显著结果。
染色体 5 上的纯合性映射结果提供了该区域可能作为一个可能包含酒精中毒遗传决定因素的区域的提示性证据。此外，原始和近亲繁殖校正谱系中偶然纯合等位基因共享的概率为这些计算所受近亲繁殖的影响提供了深入了解。
