A glycogene mutation map for discovery of diseases of glycosylation

Lars Hansen; Allan Lind-Thomsen; Hiren J Joshi; Nis Borbye Pedersen; Christian Theil Have; Yun Kong; Shengjun Wang; Thomas Sparso; Niels Grarup; Malene Bech Vester-Christensen; Katrine Schjoldager; Hudson H Freeze; Torben Hansen; Oluf Pedersen; Bernard Henrissat; Ulla Mandel; Henrik Clausen; Hans H Wandall; Eric P Bennett

doi:10.1093/glycob/cwu104

A glycogene mutation map for discovery of diseases of glycosylation

Lars Hansen, Allan Lind-Thomsen, Hiren J Joshi, Nis Borbye Pedersen, Christian Theil Have, Yun Kong, Shengjun Wang, Thomas Sparso, Niels Grarup, Malene Bech Vester-Christensen, Katrine Schjoldager, Hudson H Freeze, Torben Hansen, Oluf Pedersen, Bernard Henrissat, Ulla Mandel, Henrik Clausen, Hans H Wandall, Eric P Bennett

31 Citationer (Scopus)

Abstract

Glycosylation of proteins and lipids involves over 200 known glycosyltransferases (GTs), and deleterious defects in many of the genes encoding these enzymes cause disorders collectively classified as congenital disorders of glycosylation (CDGs). Most known CDGs are caused by defects in glycogenes that affect glycosylation globally. Many GTs are members of homologous isoenzyme families and deficiencies in individual isoenzymes may not affect glycosylation globally. In line with this, there appears to be an underrepresentation of disease-causing glycogenes among these larger isoenzyme homologous families. However, genome-wide association studies have identified such isoenzyme genes as candidates for different diseases, but validation is not straightforward without biomarkers. Large-scale whole-exome sequencing (WES) provides access to mutations in, for example, GT genes in populations, which can be used to predict and/or analyze functional deleterious mutations. Here, we constructed a draft of a functional mutational map of glycogenes, GlyMAP, from WES of a rather homogenous population of 2000 Danes. We cataloged all missense mutations and used prediction algorithms, manual inspection and in case of carbohydrate-active enzymes family GT27 experimental analysis of mutations to map deleterious mutations. GlyMAP (http://glymap.glycomics.ku.dk) provides a first global view of the genetic stability of the glycogenome and should serve as a tool for discovery of novel CDGs.

Originalsprog	Engelsk
Tidsskrift	Glycobiology
Vol/bind	25
Udgave nummer	2
Sider (fra-til)	211-224
Antal sider	14
ISSN	0959-6658
DOI	https://doi.org/10.1093/glycob/cwu104
Status	Udgivet - 1 feb. 2015

Adgang til dokumentet

10.1093/glycob/cwu104

cwu104.pdfForlagets udgivne version, 747 KB

Citationsformater

Hansen, L., Lind-Thomsen, A., Joshi, H. J., Pedersen, N. B., Have, C. T., Kong, Y., Wang, S., Sparso, T., Grarup, N., Vester-Christensen, M. B., Schjoldager, K., Freeze, H. H., Hansen, T., Pedersen, O., Henrissat, B., Mandel, U., Clausen, H., Wandall, H. H., & Bennett, E. P. (2015). A glycogene mutation map for discovery of diseases of glycosylation. Glycobiology, 25(2), 211-224. https://doi.org/10.1093/glycob/cwu104

Hansen, L, Lind-Thomsen, A, Joshi, HJ, Pedersen, NB, Have, CT, Kong, Y, Wang, S, Sparso, T, Grarup, N, Vester-Christensen, MB, Schjoldager, K, Freeze, HH, Hansen, T , Pedersen, O, Henrissat, B, Mandel, U , Clausen, H , Wandall, HH & Bennett, EP 2015, 'A glycogene mutation map for discovery of diseases of glycosylation', Glycobiology, bind 25, nr. 2, s. 211-224. https://doi.org/10.1093/glycob/cwu104

@article{bc60fa7c01f346fc9cb610c5f7a62f2c,

title = "A glycogene mutation map for discovery of diseases of glycosylation",

abstract = "Glycosylation of proteins and lipids involves over 200 known glycosyltransferases (GTs), and deleterious defects in many of the genes encoding these enzymes cause disorders collectively classified as congenital disorders of glycosylation (CDGs). Most known CDGs are caused by defects in glycogenes that affect glycosylation globally. Many GTs are members of homologous isoenzyme families and deficiencies in individual isoenzymes may not affect glycosylation globally. In line with this, there appears to be an underrepresentation of disease-causing glycogenes among these larger isoenzyme homologous families. However, genome-wide association studies have identified such isoenzyme genes as candidates for different diseases, but validation is not straightforward without biomarkers. Large-scale whole-exome sequencing (WES) provides access to mutations in, for example, GT genes in populations, which can be used to predict and/or analyze functional deleterious mutations. Here, we constructed a draft of a functional mutational map of glycogenes, GlyMAP, from WES of a rather homogenous population of 2000 Danes. We cataloged all missense mutations and used prediction algorithms, manual inspection and in case of carbohydrate-active enzymes family GT27 experimental analysis of mutations to map deleterious mutations. GlyMAP (http://glymap.glycomics.ku.dk) provides a first global view of the genetic stability of the glycogenome and should serve as a tool for discovery of novel CDGs.",

author = "Lars Hansen and Allan Lind-Thomsen and Joshi, {Hiren J} and Pedersen, {Nis Borbye} and Have, {Christian Theil} and Yun Kong and Shengjun Wang and Thomas Sparso and Niels Grarup and Vester-Christensen, {Malene Bech} and Katrine Schjoldager and Freeze, {Hudson H} and Torben Hansen and Oluf Pedersen and Bernard Henrissat and Ulla Mandel and Henrik Clausen and Wandall, {Hans H} and Bennett, {Eric P}",

year = "2015",

month = feb,

day = "1",

doi = "10.1093/glycob/cwu104",

language = "English",

volume = "25",

pages = "211--224",

journal = "Glycobiology",

issn = "0959-6658",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - A glycogene mutation map for discovery of diseases of glycosylation

AU - Hansen, Lars

AU - Lind-Thomsen, Allan

AU - Joshi, Hiren J

AU - Pedersen, Nis Borbye

AU - Have, Christian Theil

AU - Kong, Yun

AU - Wang, Shengjun

AU - Sparso, Thomas

AU - Grarup, Niels

AU - Vester-Christensen, Malene Bech

AU - Schjoldager, Katrine

AU - Freeze, Hudson H

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Henrissat, Bernard

AU - Mandel, Ulla

AU - Clausen, Henrik

AU - Wandall, Hans H

AU - Bennett, Eric P

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Glycosylation of proteins and lipids involves over 200 known glycosyltransferases (GTs), and deleterious defects in many of the genes encoding these enzymes cause disorders collectively classified as congenital disorders of glycosylation (CDGs). Most known CDGs are caused by defects in glycogenes that affect glycosylation globally. Many GTs are members of homologous isoenzyme families and deficiencies in individual isoenzymes may not affect glycosylation globally. In line with this, there appears to be an underrepresentation of disease-causing glycogenes among these larger isoenzyme homologous families. However, genome-wide association studies have identified such isoenzyme genes as candidates for different diseases, but validation is not straightforward without biomarkers. Large-scale whole-exome sequencing (WES) provides access to mutations in, for example, GT genes in populations, which can be used to predict and/or analyze functional deleterious mutations. Here, we constructed a draft of a functional mutational map of glycogenes, GlyMAP, from WES of a rather homogenous population of 2000 Danes. We cataloged all missense mutations and used prediction algorithms, manual inspection and in case of carbohydrate-active enzymes family GT27 experimental analysis of mutations to map deleterious mutations. GlyMAP (http://glymap.glycomics.ku.dk) provides a first global view of the genetic stability of the glycogenome and should serve as a tool for discovery of novel CDGs.

AB - Glycosylation of proteins and lipids involves over 200 known glycosyltransferases (GTs), and deleterious defects in many of the genes encoding these enzymes cause disorders collectively classified as congenital disorders of glycosylation (CDGs). Most known CDGs are caused by defects in glycogenes that affect glycosylation globally. Many GTs are members of homologous isoenzyme families and deficiencies in individual isoenzymes may not affect glycosylation globally. In line with this, there appears to be an underrepresentation of disease-causing glycogenes among these larger isoenzyme homologous families. However, genome-wide association studies have identified such isoenzyme genes as candidates for different diseases, but validation is not straightforward without biomarkers. Large-scale whole-exome sequencing (WES) provides access to mutations in, for example, GT genes in populations, which can be used to predict and/or analyze functional deleterious mutations. Here, we constructed a draft of a functional mutational map of glycogenes, GlyMAP, from WES of a rather homogenous population of 2000 Danes. We cataloged all missense mutations and used prediction algorithms, manual inspection and in case of carbohydrate-active enzymes family GT27 experimental analysis of mutations to map deleterious mutations. GlyMAP (http://glymap.glycomics.ku.dk) provides a first global view of the genetic stability of the glycogenome and should serve as a tool for discovery of novel CDGs.

U2 - 10.1093/glycob/cwu104

DO - 10.1093/glycob/cwu104

M3 - Journal article

C2 - 25267602

SN - 0959-6658

VL - 25

SP - 211

EP - 224

JO - Glycobiology

JF - Glycobiology

IS - 2

ER -

A glycogene mutation map for discovery of diseases of glycosylation

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater