acid-phosphatase and Xeroderma-Pigmentosum

Topics: Abortion, Induced; Acid Phosphatase; Adrenal Hyperplasia, Congenital; Amnion; Amniotic Fluid; Carbohydrate Metabolism, Inborn Errors; Congenital Abnormalities; Counseling; Culture Techniques; Cystic Fibrosis; Economics, Medical; Ethics, Medical; Female; Fetal Diseases; Fibroblasts; Genetic Diseases, Inborn; Glycogen Storage Disease; Heterozygote; Homozygote; Humans; Lysosomes; Mannose; Marfan Syndrome; Methods; Mucopolysaccharidoses; Muscular Dystrophies; Porphyrias; Pregnancy; Punctures; Xeroderma Pigmentosum

Nucleotide excision repair is a multistep process that recognizes and eliminates a spectrum of DNA damages. Five proteins, namely XPC, RAD23, Centrin 2, DDB1 and DDB2 act as a heterodimeric complex at the early steps of the NER pathway and play a crucial role in the removal of DNA lesions. Several exonic mutations on genes coding for these proteins have been identified as associated with Xeroderma-pigmentosum (XP), a rare monogenic disorder. However, the role of regulatory polymorphisms in disease development and inter-ethnic diversity is still not well documented. Due to the high incidence rate of XP in Tunisia, we performed a genotyping analysis of 140 SNPs found on these 5 genes in a set of 135-subjects representing the general Tunisian-population. An inter-ethnic comparison based on the genotype frequency of these SNPs have been also conducted. For the most relevant variants, we performed a comprehensive assessment of their functional effects. Linkage disequilibrium and principal component analysis showed that the Tunisian-population is an admixed and intermediate population between Sub-Saharan Africans and Europeans. Using variable factor maps, we identified a list of 20 polymorphisms that contribute considerably to the inter-ethnic diversity of the NER complex. In-silico functional analysis showed that SNPs on XPC, DDB1 and DDB2 are associated with eQTLs mainly DDB2-rs10838681 that seems to decrease significantly the expression level of ACP2 (p = 6.1 × 10

Topics: Acid Phosphatase; Calcium-Binding Proteins; Cell Cycle Proteins; Computational Biology; Computer Simulation; DNA Repair; DNA Repair Enzymes; DNA-Binding Proteins; Female; Gene Regulatory Networks; Humans; Linkage Disequilibrium; Male; Polymorphism, Single Nucleotide; Tunisia; Xeroderma Pigmentosum

Topics: Acid Phosphatase; Basement Membrane; Black People; Color; Dendrites; Ferritins; Humans; Lysosomes; Melanins; Melanocytes; Membranes; Middle Aged; Phagocytosis; Pigmentation; Skin; Sulfatases; Sunlight; White People; Xeroderma Pigmentosum