HGVS命名之【等位基因变异】Alleles

最近在复习HGVS命名，当做个人翻译笔记吧。

HGVS，全称是Human Genome Variation Society，人类基因组变异协会的缩写。

本周翻译的是第二部分Alleles，原文地址http://varnomen.hgvs.org/recommendations/DNA/variant/Alleles

【等位基因变异】Alleles

定义：一条染色体上的一系列变异

等位基因（allele）一般指位于一对同源染色体的相同位置上控制相对性状的一对基因。——heyi 2018-2-23 09:32:09补充

格式：

一个等位基因上的变异：前缀（所使用的参考序列）[change1;change2]，举例： g.[123G>A;345del]

两个等位基因上的变异：前缀（所使用的参考序列）[change1];[change2]，举例：g.[123G>A];[345del]

要点：

①人类是二倍体生物，每个基因位点有两个等位基因，分别遗传自父母

②当2个变异在同一条染色体上(in cis)，应描述为g.[variant1;variant2]

③当2个变异在不同染色体上(in trans)，应描述为g.[variant1];[variant2]

④当2个变异无法确定是否位于同一条染色体，应描述为variant1(;)variant2，不用[ ]；当然，最好能明确顺式/反式

⑤基于不同参考序列的2个变异，不建议应用上述规则（如c.[76A>C];g.[10091C>G]）

最新发表的指南update中，第4点应用错了，具体链接见Den Dunnen et al. (2016) ——heyi 备注

举例：

LRG_199t1:c.[2376G>C;3103del]

one allele (chromosome) of a gene contains two different changes, g.2376G>C and c.3103del. The variants are found in cis.

LRG_199t1:c.[2376G>C];[3103del]

the two alleles (chromosomes) of a gene each contain a different change, c.2376G>C and c.3103del. A heterozygous case (compound heterozygote, e.g. in a recessive disease). The variants are found in trans.

LRG_199t1:c.[2376G>C];[2376G>C]

both alleles (chromosomes) of a gene contain the same variant, c.2376G>C. A homozygous case (e.g. in a recessive disease).NOTE:it is not allowed to shorten this to c.2376[G>C];[G>C] or even c.2376G>C[];[]

隐性遗传疾病，等位基因发生相同的变异→纯合子的描述，不能缩写

LRG_199t1:c.2376G>C(;)3103del

two variants in a gene, c.2376G>C and c.3103del, but it is not known whether they are on the same or on different alleles (chromosomes).

LRG_199t1:c.[2376G>C];[(2376G>C)]

analysis detects one variant (c.2376G>C), suggesting both alleles (chromosomes) contain this variants but it can not be excluded the other allele is deleted.

“( )”用于表示不确定和预测的结果。

检测到一个突变c.2376G>C，2个等位基因都含有这个突变，但其中一个不能确定。    这个翻译不是很贴切？意译——heyi

LRG_199t1:c.[2376G>C];[?]

one allele (chromosomes) of a gene contains a variant, c.2376G>C, while a variant for the other allele is expected but not yet identified (c.?) (e.g. in individuals affected by a recessive disease).

“？”用于表示未知位置（核苷酸或氨基酸）

表明在一条染色体上明确发现c.2376G＞C突变，预测在另一条染色体上还有一个突变，具体不详

LRG_199t1:c.[296T>G;476T>C;1083A>C];[296T>G;1083A>C]

a sample contains variants c.296T>G and c.1083A>C on both alleles (chromosomes) and variant c.476C>T on only one allele.

一条染色体上有3个突变，另一条染色体上有2个突变

NM_004006.2:c.[296T>G;476T>C];[476T>C](;)1083A>C

a sample contains a homozygous variant (c.476T>C) and two heterozygous variants (c.296T>G and c.1083G>C) for which it is not known on which allele (chromosome) they are (although at least one, in the example c.296T>G, is on the same allele as c.476T>C).

共有4个突变，一对c.476T>C纯合+两个杂合c.296T>G、c.1083A>C；无法确定两个杂合突变的位置（顺式/反式）。也可表示为c.[1083A>C;476T>C];[476T>C](;)296T>G

英文解释中c.1083G>C写错了——heyi 

LRG_199t1:c.[296T>G];[476T>C](;)1083G>C(;)1406del

a sample contains heterozygous variants on different alleles (c.296T>G and c.476T>C) and two additional heterozygous variants (c.1083G>C and c.1406del) for which it is not known on which allele (chromosome) they are.

NC_000023.10:g.[30683643A>G;33038273T>G]

one allele (X-chromosome) contains two different variants in two different genes, g.30683643A>G in the GK gene and g.33038273T>G in the DMD gene.

GK和DMD是两个间隔的基因。这里把allele理解为X染色体，2个不同基因的不同突变在同一条染色体上（顺式）。

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