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在酗酒症中进行亲代来源连锁效应的基因组扫描。

A genome scan for parent-of-origin linkage effects in alcoholism.

机构信息

Program in Genetics and Genomic Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

出版信息

BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S160. doi: 10.1186/1471-2156-6-S1-S160.

DOI:10.1186/1471-2156-6-S1-S160
PMID:16451622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1866773/
Abstract

BACKGROUND

Alcoholism is a complex disease in which genomic imprinting may play an important role in its susceptibility.

OBJECTIVE

To conduct a genome-wide search for loci that may have strong parent-of-origin linkage effects in alcoholism; to compare the linkage results between the microsatellites and the two single-nucleotide polymorphism (SNP) platforms.

METHODS

Nonparametric linkage analyses were performed using ALLEGRO with the three sets of markers provided by the Genetic Analysis Workshop 14 for the Collaborative Study on the Genetics of Alcoholism Problem 1 data. Both sex-averaged and sex-specific genetic maps were used. We also provided a valid statistical test to determine whether the parental allele sharing differed significantly.

RESULTS

Significant maternal linkage effects (paternal imprinting) were observed on chromosome 12 using either the microsatellite markers or the two SNP panels. The two SNP sets did not improve the linkage signals compared to the results from the microsatellite markers on chromosome 12. Possible paternal linkage effects (maternal imprinting) on chromosome 7 and maternal linkage effects (paternal imprinting) on chromosome 10 were found using the two SNP panels.

CONCLUSION

For diseases which may have parent-of-origin effects, linkage analysis looking at parental sharing separately may reduce locus heterogeneity and increase the ability to identify that which can not be identified with usual linkage analysis.

摘要

背景

酗酒是一种复杂的疾病,基因组印记可能在其易感性中发挥重要作用。

目的

进行全基因组搜索,以寻找可能在酗酒中具有强烈亲本来源连锁效应的基因座;比较微卫星和两个单核苷酸多态性 (SNP) 平台的连锁结果。

方法

使用遗传分析研讨会 14 为酒精中毒问题 1 数据的协作研究提供的三组标记,使用 ALLEGRO 进行非参数连锁分析。使用了男女平均和性别特异性遗传图谱。我们还提供了一个有效的统计检验来确定亲本等位基因共享是否存在显著差异。

结果

使用微卫星标记或两个 SNP 面板均观察到 12 号染色体上存在显著的母系连锁效应(父系印记)。与 12 号染色体上微卫星标记的结果相比,两个 SNP 组并未改善连锁信号。使用两个 SNP 面板发现了 7 号染色体上可能存在的父系连锁效应(母系印记)和 10 号染色体上的母系连锁效应(父系印记)。

结论

对于可能具有亲本来源效应的疾病,单独观察亲本共享的连锁分析可能会减少基因座异质性,并提高识别通常的连锁分析无法识别的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/549f/1866773/b7715c58f246/1471-2156-6-S1-S160-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/549f/1866773/b7715c58f246/1471-2156-6-S1-S160-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/549f/1866773/b7715c58f246/1471-2156-6-S1-S160-1.jpg

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A combined linkage-physical map of the human genome.人类基因组的综合连锁-物理图谱。
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Association of GABA(A) receptors and alcohol dependence and the effects of genetic imprinting.γ-氨基丁酸A型(GABA(A))受体与酒精依赖的关联及基因印记的影响
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Parental sex effect in families with alcoholism.酗酒家庭中的父母性别效应。
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Linkage analysis with adequate modeling of a parent-of-origin effect.进行连锁分析,并对亲本来源效应进行充分建模。
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