Experimental long-distance haplotyping of OCA2-HERC2 variants
Permanent link
https://hdl.handle.net/10037/28229Date
2022-10-18Type
Journal articleTidsskriftartikkel
Peer reviewed
Abstract
The regulatory HERC2 SNP, rs12913832, is strongly associated with blue and brown eye colour. However, eye
colour in heterozygous rs12913832 individuals is observed to vary greatly. Missense mutations in OCA2, such as
rs1800407 and rs74653330, are associated with lighter eye colour in some but not all heterozygous rs12913832
individuals. Determining the physical linkage of these variants might help to further explain eye colour variation.
So far, experimental haplotyping of these variants has been challenging because the genomic distance between
them (~ 135 kb) exceeds the fragment lengths produced by commonly used DNA isolation kits. The aim for this
study was to explore novel methods for long distance haplotyping to assess associations between OCA2-HERC2
haplotypes and eye colour. DNA was isolated from frozen blood samples collected from Norwegians that are
known to be heterozygous for both HERC2 rs12913832 and OCA2 SNPs, either rs1800407 (n = 23) or
rs74653330 (n = 17), using the newly commercially available Monarch® HMW (heigh molecular weight) DNA
Extraction Kit (New England BioLabsinc). We successfully isolated DNA fragments up to 210 kb, which were long
enough to haplotype OCA2-HERC2 loci by droplet digital PCR (ddPCR). Three haplotypes were observed in the
study population: rs12913832:A-rs1800407:T in 22/23 individuals, rs12913832:A-rs1800407:C in 1/23 individuals and rs12913832:A-rs74653330:T in 16/16 individuals. As expected, all individuals with the
rs12913832:A-rs74653330:T haplotype had intermediate to blue eye colour. However, the rs12913832:Ars1800407:T haplotype was observed in both blue and brown-eyed individuals, suggesting more research is
needed.
Is part of
Salvo, N.M. (2024). Forensic DNA phenotyping - Towards reliable and accurate DNA tests for prediction of eye colour, hair colour and biogeographical ancestry. (Doctoral thesis). https://hdl.handle.net/10037/33807Publisher
ElsevierCitation
Salvo N, Mathisen MG, Janssen K, Berg T, Olsen G. Experimental long-distance haplotyping of OCA2-HERC2 variants. Forensic Science International: Genetics Supplement Series. 2022Metadata
Show full item recordCollections
Copyright 2022 The Author(s)