The shepherds' tale: a genome-wide study across 9 dog breeds implicates two loci in the regulation of fructosamine serum concentration in Belgian shepherds

Simon K G Forsberg; Marcin Kierczak; Ingrid Ljungvall; Anne-Christine Merveille; Vassiliki Gouni; Maria Wiberg; Jakob Willesen; Sofia Hanås; Anne-Sophie Lequarré; Louise Mejer Sørensen; Laurent Tiret; Kathleen McEntee; Eija Seppälä; Jørgen Koch; Géraldine Battaille; Hannes Lohi; Merete Fredholm; Valerie Chetboul; Jens Häggström; Örjan Carlborg; Kerstin Lindblad-Toh; Katja Höglund

doi:10.1371/journal.pone.0123173

The shepherds' tale: a genome-wide study across 9 dog breeds implicates two loci in the regulation of fructosamine serum concentration in Belgian shepherds

Simon K G Forsberg, Marcin Kierczak, Ingrid Ljungvall, Anne-Christine Merveille, Vassiliki Gouni, Maria Wiberg, Jakob Willesen, Sofia Hanås, Anne-Sophie Lequarré, Louise Mejer Sørensen, Laurent Tiret, Kathleen McEntee, Eija Seppälä, Jørgen Koch, Géraldine Battaille, Hannes Lohi, Merete Fredholm, Valerie Chetboul, Jens Häggström, Örjan CarlborgKerstin Lindblad-Toh, Katja Höglund

5 Citationer (Scopus)

169 Downloads (Pure)

Abstract

Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (pcorrected ≈ 1:68 × 10-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.

Originalsprog	Engelsk
Artikelnummer	e0123173
Tidsskrift	PLOS ONE
Vol/bind	10
Udgave nummer	5
Antal sider	17
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0123173
Status	Udgivet - 13 maj 2015

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1371/journal.pone.0123173

The Shepherd's taleForlagets udgivne version, 1,98 MB
journal.pone.0123173&type=printableForlagets udgivne version, 1,98 MBLicens: CC BY

Citationsformater

Forsberg, S. K. G., Kierczak, M., Ljungvall, I., Merveille, A-C., Gouni, V., Wiberg, M., Willesen, J., Hanås, S., Lequarré, A-S., Mejer Sørensen, L., Tiret, L., McEntee, K., Seppälä, E., Koch, J., Battaille, G., Lohi, H., Fredholm, M., Chetboul, V., Häggström, J., ... Höglund, K. (2015). The shepherds' tale: a genome-wide study across 9 dog breeds implicates two loci in the regulation of fructosamine serum concentration in Belgian shepherds. PLOS ONE, 10(5), [e0123173]. https://doi.org/10.1371/journal.pone.0123173

Forsberg, SKG, Kierczak, M, Ljungvall, I, Merveille, A-C, Gouni, V, Wiberg, M, Willesen, J, Hanås, S, Lequarré, A-S, Mejer Sørensen, L, Tiret, L, McEntee, K, Seppälä, E, Koch, J, Battaille, G, Lohi, H, Fredholm, M, Chetboul, V, Häggström, J, Carlborg, Ö, Lindblad-Toh, K & Höglund, K 2015, 'The shepherds' tale: a genome-wide study across 9 dog breeds implicates two loci in the regulation of fructosamine serum concentration in Belgian shepherds', PLOS ONE, bind 10, nr. 5, e0123173. https://doi.org/10.1371/journal.pone.0123173

@article{7be3b93770484453a57caee0bb95a5e1,

title = "The shepherds' tale: a genome-wide study across 9 dog breeds implicates two loci in the regulation of fructosamine serum concentration in Belgian shepherds",

abstract = "Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (pcorrected ≈ 1:68 × 10-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.",

author = "Forsberg, {Simon K G} and Marcin Kierczak and Ingrid Ljungvall and Anne-Christine Merveille and Vassiliki Gouni and Maria Wiberg and Jakob Willesen and Sofia Han{\aa}s and Anne-Sophie Lequarr{\'e} and {Mejer S{\o}rensen}, Louise and Laurent Tiret and Kathleen McEntee and Eija Sepp{\"a}l{\"a} and J{\o}rgen Koch and G{\'e}raldine Battaille and Hannes Lohi and Merete Fredholm and Valerie Chetboul and Jens H{\"a}ggstr{\"o}m and {\"O}rjan Carlborg and Kerstin Lindblad-Toh and Katja H{\"o}glund",

year = "2015",

month = may,

day = "13",

doi = "10.1371/journal.pone.0123173",

language = "English",

volume = "10",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

TY - JOUR

T1 - The shepherds' tale

T2 - a genome-wide study across 9 dog breeds implicates two loci in the regulation of fructosamine serum concentration in Belgian shepherds

AU - Forsberg, Simon K G

AU - Kierczak, Marcin

AU - Ljungvall, Ingrid

AU - Merveille, Anne-Christine

AU - Gouni, Vassiliki

AU - Wiberg, Maria

AU - Willesen, Jakob

AU - Hanås, Sofia

AU - Lequarré, Anne-Sophie

AU - Mejer Sørensen, Louise

AU - Tiret, Laurent

AU - McEntee, Kathleen

AU - Seppälä, Eija

AU - Koch, Jørgen

AU - Battaille, Géraldine

AU - Lohi, Hannes

AU - Fredholm, Merete

AU - Chetboul, Valerie

AU - Häggström, Jens

AU - Carlborg, Örjan

AU - Lindblad-Toh, Kerstin

AU - Höglund, Katja

PY - 2015/5/13

Y1 - 2015/5/13

N2 - Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (pcorrected ≈ 1:68 × 10-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.

AB - Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (pcorrected ≈ 1:68 × 10-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.

U2 - 10.1371/journal.pone.0123173

DO - 10.1371/journal.pone.0123173

M3 - Journal article

C2 - 25970163

SN - 1932-6203

VL - 10

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 5

M1 - e0123173

ER -

The shepherds' tale: a genome-wide study across 9 dog breeds implicates two loci in the regulation of fructosamine serum concentration in Belgian shepherds

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater