A mutation map for human glycoside hydrolase genes
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A mutation map for human glycoside hydrolase genes. / Hansen, Lars; Husein, Diab M.; Gericke, Birthe; Hansen, Torben; Pedersen, Oluf; Tambe, Mitali A.; Freeze, Hudson H.; Naim, Hassan Y.; Henrissat, Bernard; Wandall, Hans H.; Clausen, Henrik; Bennett, Eric P.
I: Glycobiology, Bind 30, Nr. 8, 2020, s. 500-515.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A mutation map for human glycoside hydrolase genes
AU - Hansen, Lars
AU - Husein, Diab M.
AU - Gericke, Birthe
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Tambe, Mitali A.
AU - Freeze, Hudson H.
AU - Naim, Hassan Y.
AU - Henrissat, Bernard
AU - Wandall, Hans H.
AU - Clausen, Henrik
AU - Bennett, Eric P.
PY - 2020
Y1 - 2020
N2 - Glycoside hydrolases (GHs) are found in all domains of life, and at least 87 distinct genes encoding proteins related to GHs are found in the human genome. GHs serve diverse functions from digestion of dietary polysaccharides to breakdown of intracellular oligosaccharides, glycoproteins, proteoglycans and glycolipids. Congenital disorders of GHs (CDGHs) represent more than 30 rare diseases caused by mutations in one of the GH genes. We previously used whole-exome sequencing of a homogenous Danish population of almost 2000 individuals to probe the incidence of deleterious mutations in the human glycosyltransferases (GTs) and developed a mutation map of human GT genes (GlyMAP-I). While deleterious disease-causing mutations in the GT genes were very rare, and in many cases lethal, we predicted deleterious mutations in GH genes to be less rare and less severe given the higher incidence of CDGHs reported worldwide. To probe the incidence of GH mutations, we constructed a mutation map of human GH-related genes (GlyMAP-II) using the Danish WES data, and correlating this with reported disease-causing mutations confirmed the higher prevalence of disease-causing mutations in several GH genes compared to GT genes. We identified 76 novel nonsynonymous single-nucleotide variations (nsSNVs) in 32 GH genes that have not been associated with a CDGH phenotype, and we experimentally validated two novel potentially damaging nsSNVs in the congenital sucrase-isomaltase deficiency gene, SI. Our study provides a global view of human GH genes and disease-causing mutations and serves as a discovery tool for novel damaging nsSNVs in CDGHs.
AB - Glycoside hydrolases (GHs) are found in all domains of life, and at least 87 distinct genes encoding proteins related to GHs are found in the human genome. GHs serve diverse functions from digestion of dietary polysaccharides to breakdown of intracellular oligosaccharides, glycoproteins, proteoglycans and glycolipids. Congenital disorders of GHs (CDGHs) represent more than 30 rare diseases caused by mutations in one of the GH genes. We previously used whole-exome sequencing of a homogenous Danish population of almost 2000 individuals to probe the incidence of deleterious mutations in the human glycosyltransferases (GTs) and developed a mutation map of human GT genes (GlyMAP-I). While deleterious disease-causing mutations in the GT genes were very rare, and in many cases lethal, we predicted deleterious mutations in GH genes to be less rare and less severe given the higher incidence of CDGHs reported worldwide. To probe the incidence of GH mutations, we constructed a mutation map of human GH-related genes (GlyMAP-II) using the Danish WES data, and correlating this with reported disease-causing mutations confirmed the higher prevalence of disease-causing mutations in several GH genes compared to GT genes. We identified 76 novel nonsynonymous single-nucleotide variations (nsSNVs) in 32 GH genes that have not been associated with a CDGH phenotype, and we experimentally validated two novel potentially damaging nsSNVs in the congenital sucrase-isomaltase deficiency gene, SI. Our study provides a global view of human GH genes and disease-causing mutations and serves as a discovery tool for novel damaging nsSNVs in CDGHs.
KW - congenital disorders of glycoside hydrolysis
KW - nsSNV
KW - WES
U2 - 10.1093/glycob/cwaa010
DO - 10.1093/glycob/cwaa010
M3 - Journal article
C2 - 32039448
AN - SCOPUS:85088608493
VL - 30
SP - 500
EP - 515
JO - Glycobiology
JF - Glycobiology
SN - 0959-6658
IS - 8
ER -
ID: 247042162