Preferential reciprocal transfer of paternal/maternal DLK1 alleles to obese children: first evidence of polar overdominance in humans.
DLK1 is part of the Notch signalling pathway that controls various developmental processes. A functional role for DLK1 in adipogenesis is suggested by several animal models. Interestingly, the DLK1 gene is imprinted in eutherian mammals. To study whether variations in DLK1 affect body weight in humans, we analysed 32 polymorphisms in a 109 kb genomic region encompassing DLK1 on human chromosome 14. In a study sample of 1025 French and German trio families comprised of both parents and extremely obese offspring we found a single nucleotide polymorphism (rs1802710) associated with child and adolescent obesity. Analysis of the allelic transmission pattern indicated the existence of polar overdominance, an unusual mode of non-Mendelian inheritance in humans previously known from the callipyge mutation in sheep.
Wermter
Anne-Kathrin
AK
Department of Child and Adolescent Psychiatry, University of Marburg, Marburg, Germany.
Scherag
André
A
Meyre
David
D
Reichwald
Kathrin
K
Durand
Emmanuelle
E
Nguyen
Thuy Trang
TT
Koberwitz
Kerstin
K
Lichtner
Peter
P
Meitinger
Thomas
T
Schäfer
Helmut
H
Hinney
Anke
A
Froguel
Philippe
P
Hebebrand
Johannes
J
Brönner
Günter
G
D000293:Adolescent; D000483:Alleles; D000818:Animals; D002135:Calcium-Binding Proteins; D002648:Child; D004195:Disease Models, Animal; D005220:Fathers; D005260:Female; D005799:Genes, Dominant; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009035:Mothers; D009765:Obesity / Q000235:genetics*; D012756:Sheep; D034421:Sus scrofa
D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins