Origin and age of the causative mutations in KLC2, IMPA1, MED25 and WNT7A unravelled through Brazilian admixed populations

Abstract

The mutation age and local ancestry of chromosomal segments harbouring mutations associated with autosomal recessive (AR) disorders in Brazilian admixed populations remain unknown; additionally, inbreeding levels for these affected individuals continue to be estimated based on genealogical information. Here, we calculated inbreeding levels using a runs of homozygosity approach, mutation age and local ancestry to infer the origin of each chromosomal segments containing disorder-causing mutations in KLC2, IMPA1, MED25 and WNT7A. Genotyped data were generated from 18 patients affected by AR diseases and combined to the 1000 genome project (1KGP) and Simons genome diversity project (SGDP) databases to infer local ancestry. We found a major European contribution for mutated haplotypes with recent mutation age and inbreeding values found only in Native American and Middle East individuals. These results contribute to identifying the origin of and to understanding how these diseases are maintained and spread in Brazilian and world populations.

Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors

“…Mutations in genes encoding other motor proteins and motor binding proteins, such as KIF5A, KIF1C and KLC2, are associated with neurodevelopmental diseases (21,23,50,51) and studies have analyzed disease-associated mutations in these genes using microtubule gliding assays (52,53). However, these studies have sometimes failed to identify the defects caused by the disease-associated mutations.…”

Haplotypes of single cancer driver genes and their local ancestry in a highly admixed long-lived population of Northeast Brazil

“…The 1KGP database, including Yoruba representing Africans, Iberians representing Europeans, and Peruvians representing admixed Native Americans, was used as described previously ( de Farias et al, 2018 ).…”

“…Because the locus-specific ancestry of cancer genomic variants in diverse populations remains unknown, in this study, we inferred the local ancestry of known cancer-associated single nucleotide polymorphisms (SNPs) and haplotypes in a highly admixed population of longevous individuals from Northeast Brazil. This region was chosen because of its high levels of admixture among European settlers, Native Americans, and enslaved Africans ( Salzano and Sans, 2014 ; Moura et al, 2015 ; Mychaleckyj et al, 2017 ; de Farias et al, 2018 ) and increased, as well as a high prevalence of consanguineous marriages compared with other regions of Brazil ( Weller et al, 2012 ).…”

Fatores associados ao uso e grau de satisfação com cadeira de rodas na Síndrome Spoa

“…A síndrome Spoan, acrônimo dos principais sintomas em inglês, é uma doença genética de herança recessiva que associa paraparesia espástica, neuropatia axonal e atrofia 1,2 . As pessoas com esta síndrome perdem gradativamente a marcha, ainda na infância, e os movimentos ficam restritos com o passar dos anos, levando a deformidades e à dependência de terceiros 3 . A maior perda funcional ocorre a partir dos 35 anos; sendo que, aos 50 anos, todos os acometidos apresentam dependência total para realização das atividades de vida diária.…”

“…O padrão de herança é autossômico recessivo e, por isso, a doença está associada aos casamentos consanguíneos 6 . Ao todo foram registradas mais de 70 pessoas com essa síndrome em dez municípios dos estados do Rio Grande do Norte e Paraíba, todas descendentes de um ancestral comum 3 . Outros casos foram diagnosticados no sudeste e Sul do Brasil e também no Egito 2 .…”