Association of five SNPs with human hair colour in the Polish population

Abstract

Twenty-two variants (single nucleotide polymorphisms - SNPs) of the genes involved in hair pigmentation (OCA2, HERC2, MC1R, SLC24A5, SLC45A2, TPCN2, TYR, TYRP1) were genotyped in a group of 186 Polish participants, representing a range of hair colours (45 red, 64 blond, 77 dark). A genotype-phenotype association analysis was performed. Using z-statistics we identified three variants highly associated with different hair colour categories (rs12913832:A>G in HERC2, rs1805007:T>C and rs1805008:C>T in MC1R). Two variants: rs1800401:C>T in OCA2 and rs16891982:C>G in SLC45A2 showed a high probability of a relation with hair colour, although that probability did not exceed the threshold of statistical significance after applying the Bonferroni correction. We created and validated mathematical logistic regression models in order to test the usefulness of the sets of polymorphisms for hair colour prediction in the Polish population. We subjected four models to stratified cross-validation. The first model consisted of three polymorphisms that proved to be important in the associative analysis. The second model included, apart from the mentioned polymorphisms, additionally rs16891982:C>G in SLC45A. The third model included, apart from the variants relevant in the associating analysis, rs1800401:C>T in OCA. The fourth model consisted of the set of polymorphisms from the first model supplemented with rs16891982:C>G in SLC45A and rs1800401:C>T in OCA. The validation of our models has shown that the inclusion of rs16891982:C>G in SLC45A and rs1800401:C>T in OCA increases the prediction of red hair in comparison with the algorithm including only rs12913832:A>G in HERC2, rs1805007:T>C and rs1805008:C>T in MC1R. The model consisting of all the five above-mentioned genetic variants has shown good prediction accuracies, expressed by the area under the curve (AUC) of the receiver operating characteristics: 0.84 for the red-haired, 0.82 for the dark-haired and 0.71 for the blond-haired. A genotype-phenotype association analysis brought results similar to those in other studies and confirmed the role of rs16891982:C>G, rs12913832:A>G, rs1805007:T>C and rs1805008:C>T in hair colour determination in the Polish population. Our study demonstrated for the first time the possibility of a share of the rs1800401:C>T SNP in the OCA2 gene in hair colour determination. Including this single nucleotide polymorphism in the actual hair colour predicting models would improve their predictive accuracy.

The distinctive geographic patterns of common pigmentation variants at the OCA2 gene

“…Additional individual SNP frequencies were obtained primarily from the published literature and were entered into the ALFRED database ( https://alfred.med.yale.edu ) before it became static. A fourth amino acid substitution, rs1800401 (Arg305Trp), has been typed in the 1 KG samples but is not included here because it has been otherwise studied largely in samples defined by pigmentation phenotypes (eye, hair, skin color) in a few populations 3 , 24 , 25 . The rare amino acid change (Val443Ile) at SNP rs121918166 has only been studied on a small number of European populations 10 and studied for its effect on eye, hair, and skin color.…”

Considering the flanking region variants of nonbinary SNP and phenotype‐informative SNP to constitute 30 microhaplotype loci for increasing the discriminative ability of forensic applications

“…The actual mutation rate of microhaplotype should be researched in several generations and many parent-child pairs. Moreover, the piSNPs of selected phenotypic microhaplotype loci were fully investigated in many genome-wide association studies (GWAS), and have proved they all had strong association with some visual characteristics [44][45][46][47][48][49]. For example, the hair color was one of the most visual characteristics and strongly controlled by genes.…”

“…The SNP rs16891982 of mh05pi001 was located on the SLC45A2 gene, which encoded the membraneassociated transporter protein and mediated the formation of melanin [45]. The study in population of the University of Arizona has shown that the SNP rs16891982 and the hair color yield an R 2 of 0.637, and the study of Polish has suggested there was a strong correlation between the SNP rs16891982 and the hair color [45,46]. The TYRP1 gene controlled a key enzymatic step in melanin biosynthesis, and the SNP rs13289810 of mh09pi001 located on TYRP1 gene had the strongest correlation with the blonde and dark hair [47].…”

Biobank Lodz – population based biobank at the University of Lodz, Lodz, Poland

“…DNA, RNA tests (DNA and RNA isolation from various biological materials), study of genetic variation using classical methods of molecular biology such as: PCR, real-time PCR, Sanger sequencing [18], high-resolution melting of PCR products (HRM) [3-4, 17, 21, 26, 44-45], Taq-Man probes, measurements of selected parameters of the tested material (fluorometric testing of the DNA concentration), separation of nucleic acids using horizontal, vertical, capillary electrophoresis, genomic DNA testing using microarrays (e.g. GWAS) [15-16, 20, 22-23], next generation sequencing (Illumina Platform, Nanopore Sequencing), gene expression testing (RNA-seq, microarray and qPCR) [46][47][48][49][50][51], epigenetic analysis (Chip-Seq, DNA methylation analysis, methylation RNA), microorganism genome analysis (de novo sequencing, variant calling) [44,[52][53][54][55][56][57], eukaryotes whole genome and targeting sequencing, aDNA analysis [58][59], human genome analysis (variant calling, NGS Target Enrichment, whole exome sequencing), amplicon sequencing, metagenomics and metabarcoding, bioinformatics analysis.…”

“…; DNA; the collection was created for the project TESTOPLEK; retrospective; anonymized; POPULOUS_ BLUL[3][4][15][16][17][18][19][20][21][22][23].…”