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關(guān)于近交系數(shù)是什么的定義，除了英文資料，中文上也給出了清晰的定義，這里引用一下：
近交系數(shù)（inbreeding coefficient）是指根據(jù)近親交配的世代數(shù)，將基因的純化程度用百分?jǐn)?shù)來(lái)表示即為近交系數(shù)，也指?jìng)€(gè)體由于近交而造成異質(zhì)基因減少時(shí)，同質(zhì)基因或純合子所占的百分比也叫近交系數(shù)，普遍以F或f來(lái)表示。
GATK近交系數(shù)的計(jì)算程序在github上可以找到：AS_InbreedingCoeff.java
代碼不短，但計(jì)算很簡(jiǎn)單，我主要說(shuō)展示一下這個(gè)計(jì)算的核心部分并在代碼中做些注釋，如下：
protected double calculateIC(final VariantContext vc, final Allele altAllele) {
final int AN = vc.getCalledChrCount();
final double altAF;
final double hetCount = heterozygosityUtils.getHetCount(vc, altAllele);
final double F;
//shortcut to get a value closer to the non-alleleSpecific value for bialleleics
if (vc.isBiallelic()) {
double refAC = heterozygosityUtils.getAlleleCount(vc, vc.getReference());
double altAC = heterozygosityUtils.getAlleleCount(vc, altAllele);
double refAF = refAC/(altAC+refAC);
altAF = 1 - refAF;
F = 1.0 - (hetCount / (2.0 * refAF * altAF * (double) heterozygosityUtils.getSampleCount())); // inbreeding coefficient
} else {
//compare number of hets for this allele (and any other second allele) with the expectation based on AFs
//derive the altAF from the likelihoods to account for any accumulation of fractional counts from non-primary likelihoods,
//e.g. for a GQ10 variant, the probability of the call will be ~0.9 and the second best call will be ~0.1 so adding up those 0.1s for het counts can dramatically change the AF compared with integer counts
altAF = heterozygosityUtils.getAlleleCount(vc, altAllele)/ (double) AN;
// 計(jì)算inbreeding coefficient
F = 1.0 - (hetCount / (2.0 * (1 - altAF) * altAF * (double) heterozygosityUtils.getSampleCount())); // heterozygosityUtils.getSampleCount() 獲取總樣本數(shù)
}
return F;
}
總的來(lái)說(shuō)，是利用哈迪溫伯格定律來(lái)計(jì)算的。 1.0 - (hetCount / (2.0 * (1 - altAF) * altAF(double)N ，N是人數(shù)。這個(gè)值給出的是期望的雜合變異的個(gè)數(shù)。所以參數(shù)F說(shuō)的就是"實(shí)際的hetCount”除以"期望的hetCount"再與1.0取差。當(dāng)F值越接近0，就意味著實(shí)際的hetCount與理論的hetCount越接近。
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