PMID- 17406643
OWN - NLM
STAT- MEDLINE
DCOM- 20070724
LR  - 20070621
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 15
IP  - 7
DP  - 2007 Jul
TI  - Transmission ratio distortion and maternal effects confound the analysis of 
      modulators of cystic fibrosis disease severity on 19q13.
PG  - 774-8
AB  - Two entities localised within in a 5 Mb interval on 19q13, that is the 
      transforming growth factor beta 1 (TGFbeta1) and the cystic fibrosis modifier 1, 
      have been reported to modulate disease severity of cystic fibrosis (CF), albeit 
      the designation of the risk allele for TGFbeta1 differs between studies. We have 
      analysed genotyping data at seven microsatellite loci and four single nucleotide 
      polymorphisms targeting the 19q13 area from 37 nuclear CF families with two 
      affected offspring exhibiting extreme clinical phenotypes for indicators of 
      transmission-ration distortion, maternal genetic or maternal non-genetic effects. 
      Evidence for a transmission-ratio distortion was obtained at D19S112 (P=0.0304) 
      near the recently characterised myotonic dystrophy locus myotonic dystrophy 
      protein kinase (DMPK). Maternal and paternal genotype distributions were 
      significantly different at rs1982073 (Leu10Pro at TGFbeta1) whereby all CF sibs 
      heterozygous at rs1982073 inherited the Leu10 allele from their mother 
      (P=0.000132) in our sibling panel. To ask whether the improved survival in CF 
      over the last decades has any influence on TGFbeta1 allele frequencies, we 
      analysed unrelated F508del homozygotes who were stratified by birth cohort. 
      Sensitivity with respect to the survivor bias was reflected by significantly 
      higher incidence of mild cystic fibrosis transmembrane conductance regulator 
      mutation genotypes in the early born patient cohort (P=0.0169), and an allelic 
      imbalance was also observed at TGFbeta1 (P=0.0664). In conclusion, the role of 
      TGFbeta1 as a CF modulator, suggested from studies with a case-control setting, 
      needs to be interpreted with caution unless family-based analysis is carried out 
      to identify parental genetic and non-genetic effects.
FAU - Becker, Tim
AU  - Becker T
AD  - Institute of Medical Biometrics, Informatics and Genetics (IMBIE), University of 
      Bonn, Bonn, Germany.
FAU - Jansen, Silke
AU  - Jansen S
FAU - Tamm, Stephanie
AU  - Tamm S
FAU - Wienker, Thomas F
AU  - Wienker TF
FAU - Tummler, Burkhard
AU  - Tummler B
FAU - Stanke, Frauke
AU  - Stanke F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Twin Study
DEP - 20070404
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (CFTR protein, human)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
SB  - IM
MH  - Chromosomes, Human, Pair 19/*genetics
MH  - Cohort Studies
MH  - Cystic Fibrosis/*genetics
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/*genetics
MH  - Gene Frequency
MH  - Humans
MH  - Microsatellite Repeats
MH  - Mothers
MH  - Polymorphism, Single Nucleotide
MH  - Transforming Growth Factor beta1/genetics
EDAT- 2007/04/05 09:00
MHDA- 2007/07/25 09:00
CRDT- 2007/04/05 09:00
PHST- 2007/04/05 09:00 [pubmed]
PHST- 2007/07/25 09:00 [medline]
PHST- 2007/04/05 09:00 [entrez]
AID - 5201825 [pii]
AID - 10.1038/sj.ejhg.5201825 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2007 Jul;15(7):774-8. doi: 10.1038/sj.ejhg.5201825. Epub 2007 
      Apr 4.