Exploring a SNP in human
The missense variation rs61746355 in the human KRT6B gene has been reported in patients with delayed‐onset pachyonychia congenita (PC). This SNP is also referred to as ‘c.1495G>A’ or ‘p.Gly499Ser’.
(a) Find the page with information for rs61746355.
(b) What sequence ontology (SO) terms, or variant consequence types, are associated with rs61746355? What are the amino acid changes?
(c) Why are the alleles for this variant in Ensembl given as C/A and not as G/T, as in the literature?
(d) What is the major allele of rs61746355 in different populations?
(e) In which paper(s) is the association between rs61746355 and PC described?
(f) According to the data imported from dbSNP, the ancestral allele for rs61746355 is C. Ancestral alleles in dbSNP are based on a comparison between human and chimp. Does the sequence at this same position in other primates confirm that the ancestral allele is C?
(a) Go to the Ensembl homepage.
Type rs61746355 in the Search box, then click Go.
(b) Click on Genes and Regulation in the left-hand menu (or the Genes and Regulation icon under Explore this variant).
The rs61746355 variant is a missense variant. Please note that this variant is multi-alleleic with two alternative alleles A and C. The table displays one consequence per row, with each transcript being listed twice. The amino acid change is G/C for allele A, and G/S for allele T.
(c) In Ensembl, the alleles of rs61746355 are given as C/A/T. You can find this at the top of the page under Alleles.
This is because these are the alleles in the forward strand of the genome. In the literature, the alleles are given as G/T/A because the KRT6B gene is located on the reverse strand. The alleles in the actual gene and transcript sequences are G/T/A. In Ensembl, the allele that is present in the reference genome assembly is always put first.
(d) Click on Population genetics in the side menu.
In all populations, the allele C is the major one.
(e) Click on Phenotype Data in the left hand side menu.
The specific studies where the association was originally described is given in Phenotype data in the left-hand menu. A link between rs61746355 and PC was described in 1 paper. Click on the PubMed ID PMID:24354895 to view the publication.
(f) Click on Phylogenetic Context in the left-hand menu. Select Alignment: 10 primates EPO and click Apply.
Bonobo, chimpanzee, crab-eating macaque, gibbon, gorilla, macaque, mouse lemur and sumatran orangutan all have a C allele in this position. Chlorocebus sabaeus (vervet-AGM) has an A allele at this position.
