Beyond Homozygosity Mapping: Family-Control analysis based on Hamming distance for prioritizing variants in exome sequencing.
Beyond Homozygosity Mapping: Family-Control analysis based on Hamming distance for prioritizing variants in exome sequencing.
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除了纯合性映射外：基于锤距的家庭控制分析，用于优先考虑外显子测序中的变体。
DOI：
10.1038/srep12028
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发表时间：
2015-07-06
影响因子：
4.6
通讯作者：
Ott J
中科院分区：
文献类型：
--
作者：
Imai A;Nakaya A;Fahiminiya S;Tétreault M;Majewski J;Sakata Y;Takashima S;Lathrop M;Ott J
目前常染色体隐性遗传（AR）家族外显子组测序的一个主要挑战是缺乏一种有效的方法来优先考虑单核苷酸变异（SNV）。AR家族通常太小而无法进行连锁分析，纯合区域的长度对于鉴定致病性变体是不可靠的。各种常见的过滤步骤通常会产生一系列候选变体，这些变体无法进一步缩小范围或进行排名。为了优先考虑入围的SNVs，我们考虑每个纯合候选变异连同一组SNVs侧翼it.We比较了受影响的家庭成员和一些控制个体之间的基因型阵列，并认为，在一个家庭中，家庭成员和控制之间的差异应该是较大的致病性变异和SNVs侧翼它比随机变异。我们通过汉明距离评估两个个体中阵列之间的差异，并开发出合适的检验统计量，预计对于致病变异和侧翼SNV而言，该检验统计量较大。我们根据这一统计数据对候选变异进行了优先排序，并将我们的方法应用于6名具有已知致病变异的患者，发现这些患者处于前2至10位。
A major challenge in current exome sequencing in autosomal recessive (AR) families is the lack of an effective method to prioritize single-nucleotide variants (SNVs). AR families are generally too small for linkage analysis, and length of homozygous regions is unreliable for identification of causative variants. Various common filtering steps usually result in a list of candidate variants that cannot be narrowed down further or ranked. To prioritize shortlisted SNVs we consider each homozygous candidate variant together with a set of SNVs flanking it. We compare the resulting array of genotypes between an affected family member and a number of control individuals and argue that, in a family, differences between family member and controls should be larger for a pathogenic variant and SNVs flanking it than for a random variant. We assess differences between arrays in two individuals by the Hamming distance and develop a suitable test statistic, which is expected to be large for a causative variant and flanking SNVs. We prioritize candidate variants based on this statistic and applied our approach to six patients with known pathogenic variants and found these to be in the top 2 to 10 percentiles of ranks.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4
作者：
Rauch, Frank;Moffatt, Pierre;Glorieux, Francis H.
通讯作者：
Glorieux, Francis H.
影响因子：
4
作者：
Srour, Myriam;Hamdan, Fadi F.;Michaud, Jacques L.
通讯作者：
Michaud, Jacques L.
影响因子：
3.5
作者：
Fahiminiya, Somayyeh;Al-Jallad, Hadil;Rauch, Frank
通讯作者：
Rauch, Frank
DOI：
10.1016/j.jaci.2013.06.013
发表时间：
2013-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Chen R;Giliani S;Lanzi G;Mias GI;Lonardi S;Dobbs K;Manis J;Im H;Gallagher JE;Phanstiel DH;Euskirchen G;Lacroute P;Bettinger K;Moratto D;Weinacht K;Montin D;Gallo E;Mangili G;Porta F;Notarangelo LD;Pedretti S;Al-Herz W;Alfahdli W;Comeau AM;Traister RS;Pai SY;Carella G;Facchetti F;Nadeau KC;Snyder M;Notarangelo LD
通讯作者：
Notarangelo LD