What are variants, alleles and haplotypes?

What are variants?

In the field of genetic variation, the term variant is used to refer to a specific region of the genome which differs between two genomes.
通常我们所说的变异其实是相对于参考基因组来说的。如果没有这个参考基因组，何谈变异。按照这个定义，变异其实说的是两个基因组不同的区域。那么，单核苷酸变异说的不同人之间单个base的变异。可以叫做snv （single-nucleotide variant)），但是还不能被叫snp (single-nucleotide polymorphism) 。

snv和snp之间区别请移步公众号搜索“理清SNP、SNV、CNV等一些概念”。
snp和snv很多时候被混着叫。snp的概念重心在于多态性，描述的是一个群体性的概念。这个单位点的变异存在于一个群体之中，当然这个频率是多少不一定。

snv描述的是少数个体之间，相对于参考基因组，某个位点的变异。

What are alleles?

那么知道snp后，后面一个概念是allele，翻译过来是等位基因。
关于等位基因概念allele请移步公众号搜索“一叶知因丨基因科普微视频之Allele”。
说简单点，就是同源染色体上，同一个基因座上的一对基因。一个来自父亲，一个来自母亲。当然，等位基因可能完全一样，也可能部分序列不一样。

这个和我们遗传学上课本学的等位基因的概念还有些不同。

进行群体的重测序后，我们要call snp。
按照以下EBI的描述，说的是同一个snp位置，参考基因组那个碱基就是reference allele；你的重测序个体那个snp就是alternative allele。
那么，接下来就引出另一个概念，snp二态性（snp biallelic）。
虽然base有acgt四种，但是对于基因组某个位置确定的碱基只有一个，也就是说具体到某个snp其实就是两种形态，比如C/T。他们非此即彼。
有了snp allele的概念，就很容易理解haplotype了。翻译为单倍型。简单理解就是一条染色体上，连续的一段snp。下图清晰地展示了haplotype。AGT/GTA/AGA是三种不同类型的单倍型。

那么问题来了，为了什么要区分不同的单倍型？

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图片来自：https://sg.idtdna.com/pages/education/decoded/article/genotyping-terms-to-know

Different versions of the same variant are called alleles. For example, a SNP may have two alternative bases, or alleles, C and T⁴.

When working with genome scale data the term reference allele refers to the base that is found in the reference genome. Since the reference is just somebody’s genome, it is not always the major allele. In contrast, the alternative allele refers to any base, other than the reference, that is found at that locus. The alternative allele is not necessarily the minor allele and it may, or may not, be linked to a phenotype. There can be more than one alternative allele per variant.

What is linkage disequilibrium?

In the genome, alleles at variants close together on the same chromosome tend to occur together more often than is expected by chance. These blocks of alleles are called haplotypes. Linkage disequilibrium (LD) is a measure of how often two alleles or specific sequences are inherited together, with alleles that are always co-inherited said to be in linkage disequilibrium.
不知道理解到位不？后续再理解，加点图
未完，待续

以上内容来源：
https://www.ebi.ac.uk/training/online/courses/human-genetic-variation-introduction/what-is-genetic-variation/what-are-variants-alleles-and-haplotypes/