Long-read sequencing enables the accurate annotation of immune gene clusters in goat

Authors: Bickhart, Derek; SCHWARTZ, JOHN - The Pirbright Institute; HAMMOND, JOHN - The Pirbright Institute; Rosen, Benjamin - Ben; KOREN, SERGEY - National Institutes Of Health (NIH); MEDRANO, JUAN - University Of California, Davis; PHILLIPPY, ADAM - National Institutes Of Health (NIH); Van Tassell, Curtis - Curt; Smith, Timothy - Tim

Submitted to: International Plant and Animal Genome IX Conference
Publication Type: Abstract Only
Publication Acceptance Date: 1/16/2018
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Repetitive and polymorphic immune gene clusters have remained difficult to characterize and compare among most livestock species. This represents a significant issue within the field of livestock genomics, as alleles of genes related to the adaptive and innate immune system likely influence animal health outcomes in practice, yet remain difficult to track with existing genotyping tools. The development of third-generation sequencing platforms and advanced scaffolding methods has finally enabled the accurate characterization of these regions, de novo, and has already revealed interesting differences among ruminant species. We used the recent long-read assembly (ARS1) of the domestic goat (Capra hircus) as an example of how newer sequencing technologies and assembly methods can fully characterize previously recalcitrant immune gene regions in Eukaryotic genomes. The natural killer cell (NKC) immune gene cluster, which consists of a large number of cell-surface receptor encoding genes that are expressed in NKC lymphocytes, was present on a single contig in the current ARS1 version of the goat reference genome. This represented a 53-fold improvement in contiguity over the prior goat reference genome version, and it confirmed a previously discovered duplication of the locus that is specific to ruminant species. The full characterization of the structure of these regions revealed a large gap in current marker-assisted selection efforts, as many immune gene regions lack even a single internal SNP marker in current genotyping tools. In the Caprine 50k SNP chip, the goat IGHV region had no internal SNP markers, whereas the IGKV, IGLV and NKC regions had 3, 5, and 3 internal markers, respectively. With new, highly contiguous assemblies of these regions, additional SNP markers can be selected to track unique alleles for downstream genomic selection efforts.