AI Article Synopsis
- Researchers sequenced the genomes of 6 family members from a consanguineous tribe in Pakistan to study dwarfism, focusing on identifying the causal variants.
- They discovered a specific missense variant, rs111033552, in the COL10A1 gene likely linked to the dwarfism condition, confirmed through Sanger sequencing in 22 family members.
- The identified mutation is unique to affected family members and not found in a large population sample, strengthening its association with the dwarfism phenotype.
Article Abstract
Disease-associated variants in the human genome are continually being identified using DNA sequencing technologies that are especially effective for Mendelian disorders. Here we sequenced whole genome to high coverage (>30×) of 6 members of a 7-generation family with dwarfism from a consanguineous tribe in Pakistan to determine the causal variant(s). We identified a missense variant rs111033552 (c.2011T>C [p.Ser671Pro]) located in COL10A1 (encodes the alpha chain of type X collagen) as the most likely contributor to the dwarfism. We further confirmed the variant in 22 family members using Sanger sequencing. All affected individuals are heterozygous for the missense mutation rs111033552 and no individual homozygous was observed. Moreover, the mutation was absent in 69,985 individuals representing >150 global populations. Taking advantage of whole-genome sequencing data, we also examined other variant forms, including copy number variation and insertion/deletion, but failed to identify such variants enriched in the affected individuals. Thus rs111033552 had priority for linkage with dwarfism.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837121 | PMC |
| http://dx.doi.org/10.1038/s41437-017-0021-6 | DOI Listing |
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