TY - JOUR
T1 - Single-nucleotide variations in the genes encoding the mitochondrial Hsp60/Hsp10 chaperone system and their disease-causing potential
AU - Bross, Peter
AU - Li, Zhijie
AU - Hansen, Jakob
AU - Hansen, Jens Jacob
AU - Nielsen, Marit Nyholm
AU - Corydon, Thomas Juhl
AU - Georgopoulos, Costa
AU - Ang, Debbie
AU - Lundemose, Jytte Banner
AU - Niezen-Koning, Klary
AU - Eiberg, Hans Rudolf Lytchoff
AU - Yang, Huanming
AU - Kølvraa, Steen
AU - Bolund, Lars
AU - Gregersen, Niels
PY - 2007
Y1 - 2007
N2 - Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM: *606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.
AB - Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM: *606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.
KW - Butyryl-CoA Dehydrogenase
KW - Chaperonin 10
KW - Chaperonin 60
KW - Child
KW - Child, Preschool
KW - Genetic Predisposition to Disease
KW - Humans
KW - Infant
KW - Infant, Newborn
KW - Malonates
KW - Mitochondrial Proteins
KW - Polymorphism, Single Nucleotide
KW - Promoter Regions, Genetic
KW - Sudden Infant Death
U2 - 10.1007/s10038-006-0080-7
DO - 10.1007/s10038-006-0080-7
M3 - Journal article
C2 - 17072495
SN - 1434-5161
VL - 52
SP - 56
EP - 65
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 1
ER -