Transmission ratio distortion in the myotonic dystrophy locus in human preimplantation embryos.
One form of myotonic dystrophy, dystrophia myotonica 1 (DM1), is caused by the expansion of a (CTG)(n) repeat within the dystrophia myotonica-protein kinase (DMPK) gene located in chromosome region 19q13.3. Unaffected individuals carry alleles with repeat size (CTG)(5-37), premutation carriers (CTG)(38-49) and DM1 affected individuals (CTG)(50-6,000). Preferential transmission both of expanded repeats from DM1-affected parents and larger DMPK alleles in the normal-size range have been reported in live-born offspring. To determine the moment in development when transmission ratio distortion (TRD) for larger normal-size DMPK alleles is generated, the transmission from heterozygous parents with one repeat within the (CTG)(5-18) range (Group I repeat) and the other within the (CTG)(19-37) range (Group II repeat) to human preimplantation embryos was analysed. A statistically significant TRD of 59% (95% confidence interval of 54-64) in favour of Group II repeats from both mothers and fathers was observed in preimplantation embryos, which remained significant when female embryos were considered separately. In contrast, no significant TRD was detected for repeats from informative Group I/Group I parents. Our analysis showed that Group II repeats specifically were preferentially transmitted in human preimplantation embryos. We suggest that TRD, in Group II repeats at the DMPK locus, is likely to result from events occurring at or around the time of fertilisation.
Dean
Nicola L
NL
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.
Loredo-Osti
J Concepción
JC
Fujiwara
T Mary
TM
Morgan
Kenneth
K
Tan
Seang Lin
SL
Naumova
Anna K
AK
Ao
Asangla
A
D000483:Alleles; D001755:Blastocyst; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004622:Embryo, Mammalian / Q000378:metabolism; D005220:Fathers; D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D009035:Mothers; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D013094:Spermatozoa / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion
C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases