Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions

Factors Associated with Mutations: Their Matching Rates to Cardiovascular and Neurological Diseases

“…With a myriad of intriguing mismatches between the two considered factors and EH obtained through microsatellite markers, we asked what differed in the EH study of Figure 1 as compared to the previous investigations on CNS disorders [ 4 ]. Using the refined literature search mentioned in the methods section, we investigated the position of 79 genes near the loci proposed for hypertension ( Table S2 ).…”

“…With the advent of new molecular techniques, genetic mutations linked to monogenic hypertension (MH) have been found, suggesting that understanding the pathologies of these monogenic disorders provides insight into the causes of the more prevalent essential hypertension (EH) and new avenues to unravel the complexities of blood pressure regulation [ 3 ]. We have recently demonstrated that mutations causative of the congenital disorder can be projected by a stochastic approach centered on chromosomal characteristics of human genomes [ 4 ]. Germline mutations, which are created by homologous recombination, are estimated to occur in humans with an average probability of 1.28 × 10 −8 per site per generation, with ∼93% of these being point mutations [ 5 , 6 ].…”

“…On the other hand, associated genes are those in which the cause and effect of the gene and its phenotype cannot be explained by genetic factors alone. Genes associated with essential hypertension (EH) and Alzheimer’s disease [ 4 ] are valid examples of how genetic and environmental factors may both contribute to the disease phenotype. In this study, we also use the term ‘genetic susceptibility’ when we refer to a candidate gene susceptible to the disease with an additional contributor [ 14 ].…”

“…Several factors have been reported to be associated with high mutation rates, including recombination rate, proximity to a telomere (F(i)) [ 30 ], and high A+T content (F(ii)) [ 9 , 12 , 31 ]. Among these factors, we have previously shown that F(i) [ 8 ] and F(ii) can explain some of the genetic mutations linked to monogenic and/or degenerative disorders [ 4 ]. However, whether these factors can provide a quantitative clue by percent on the genetic and/or environmental contributions to CVDs remains unclear.…”

“…Here, we investigate the two aforementioned chromosomal factors to determine whether they are associated with high mutation rates in human genes related to CVDs. By analyzing the sets of genes published previously for hypertension, CHD, and TAA, we aim to determine how many genes satisfy the two factors F(i) and F(ii) [ 4 , 12 ]. To do so, we compare the matching rate of these two criteria to the disease, focusing on the gene transcripts and/or genes near the loci involving coding and non-coding regions obtained from four independent prior studies.…”