The following is a summary of “A Neanderthal haplotype introgressed into the human genome confers protection against membranous nephropathy,” published in the February 2024 issue of Nephrology by Voinescu et al.
Class 2 HLA and PLA2R1 alleles are robust genetic risk factors for membranous nephropathy (MN). The influence of introgressed archaic haplotypes on phenotypes through gene dysregulation is unknown.
Researchers conducted a prospective study investigating the genomic region near the PLA2R1 gene and assessing the impact of introgressed Neanderthal haplotypes on MN susceptibility.
They calculated the probability of clustering due to introgression or common descent by reconstructing the phylogeny of Neanderthal and modern haplotypes in the PLA2R1 region. Variants were imputed for participants from a previous genome-wide association study. Neanderthal variant distribution between MN cases and controls was compared.
The results showed that the PLA2R1 gene’s region, associated with the primary MN risk locus, contained a 507 kb introgressed sequence. Within this, a 105 kb haplotype overlapping PLA2R1 and ITGB6 coding regions originated from Neanderthals. Neanderthal haplotypes intersecting PLA2R1 were differentially represented in MN cases and controls, with controls showing enrichment, suggesting a protective effect.
Investigators concluded that introgressed Neanderthal haplotypes overlapping PLA2R1 are associated with differential representation in MN cases and control. This suggests a potential protective effect against membranous nephropathy.
Source: kidney-international.org/article/S0085-2538(24)00073-5/fulltext
