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Revisiting the potential power of human leukocyte antigen (HLA) genes on relationship testing by massively parallel sequencing-based HLA typing in an extended family

Revisiting the potential power of human leukocyte antigen (HLA) genes on relationship testing by massively parallel sequencing-based HLA typing in an extended family

Abstract:

The human leukocyte antigen (HLA) genes are the most polymorphic genes in the human genome and have great power in forensic applications, especially in relationship testing and personal identification. However, the extreme polymorphism of HLA has made unambiguous genotyping of these genes very challenging and resulted in the limited application in relationship testing. Fortunately, massively parallel sequencing (MPS) technology offers the promise of unambiguous and high-throughput HLA typing. In this study, 11 HLA genes were typed in one extended family residing in North China and encompassing six generations. Phase-resolved genotypes for HLA genes were generated and HLA haplotype structure was defined. The paternity/kinship index, or in other words, likelihood ratio (LR) was calculated. A total of 88 alleles were identified, of which eight alleles were newly discovered. The inheritance of HLA alleles followed Mendelian law. With the discovery of new HLA alleles and three recombination events, a total of eleven new HLA haplotypes were identified in this population. LR distribution showed that, when HLA alleles were applied, the Log10LR for a single locus could reach very high and the median average Log10LRs of HLA genes were much higher than that of short tandem repeat loci. The result showed that high-throughput HLA genotyping could be achieved rapidly by MPS, and the contribution of HLA genes on system performance could be high, which may be applied as a supplement in forensic genetics studies. This study was also valuable in demonstrating the genetic mechanisms governing the generation of polymorphisms of the HLA genes.

Citation:

  • Wu, R., Li, H., Peng, D., Li, R., Zhang, Y., Hao, B., Huang, E., Zheng, C. and Sun, H. (2018). Revisiting the potential power of human leukocyte antigen (HLA) genes on relationship testing by massively parallel sequencing-based HLA typing in an extended family. Journal of Human Genetics, -, -.

Source Link:
https://www.nature.com/articles/s10038-018-0521-0

Keywords

Peoples: Chinese | Places: North China | Topics: Family Reconstruction and HLA | DNA Type:

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