The Genome Center, University of California, Davis, USA.
The Plant Biology Graduate Group, University of California, Davis, CA, 95616, USA.
BMC Bioinformatics. 2022 Apr 25;23(1):150. doi: 10.1186/s12859-022-04685-z.
Polyploidy and heterokaryosis are common and consequential genetic phenomena that increase the number of haplotypes in an organism and complicate whole-genome sequence analysis. Allele balance has been used to infer polyploidy and heterokaryosis in diverse organisms using read sets sequenced to greater than 50× whole-genome coverage. However, sequencing to adequate depth is costly if applied to multiple individuals or large genomes.
We developed VCFvariance.pl to utilize the variance of allele balance to infer polyploidy and/or heterokaryosis at low sequence coverage. This analysis requires as little as 10× whole-genome coverage and reduces the allele balance profile down to a single value, which can be used to determine if an individual has two or more haplotypes. This approach was validated using simulated, synthetic, and authentic read sets from the oomycete species Bremia lactucae and Phytophthora infestans, the fungal species Saccharomyces cerevisiae, and the plant species Arabidopsis arenosa. This approach was deployed to determine that nine of 21 genotyped European race-type isolates of Bremia lactucae were inconsistent with diploidy and therefore likely heterokaryotic.
Variance of allele balance is a reliable metric to detect departures from a diploid state, including polyploidy, heterokaryosis, a mixed sample, or chromosomal copy number variation. Deploying this strategy is computationally inexpensive, can reduce the cost of sequencing by up to 80%, and used to test any organism.
多倍体和异核现象是常见且重要的遗传现象，它们增加了生物体中的单倍型数量，并使全基因组序列分析变得复杂。等位基因平衡已被用于推断不同生物体的多倍体和异核现象，使用测序深度大于 50 倍全基因组覆盖的读取集。然而，如果应用于多个个体或大型基因组，测序到足够的深度是昂贵的。
我们开发了 VCFvariance.pl，以利用等位基因平衡的方差推断低测序深度下的多倍体和/或异核现象。这种分析只需 10 倍全基因组覆盖，将等位基因平衡谱简化为单个值，可用于确定个体是否具有两个或更多单倍型。该方法使用来自卵菌物种乳疫霉和致病疫霉、真菌物种酿酒酵母和植物物种砂生阿瑞氏菊的模拟、合成和真实读取集进行了验证。该方法用于确定 21 个欧洲菌系乳疫霉基因型中有 9 个与二倍体不一致，因此可能是异核的。
等位基因平衡的方差是检测偏离二倍体状态的可靠指标，包括多倍体、异核现象、混合样本或染色体拷贝数变异。部署这种策略在计算上成本低廉，可将测序成本降低高达 80%，并可用于测试任何生物体。
