PMID- 10677311
OWN - NLM
STAT- MEDLINE
DCOM- 20000330
LR  - 20240510
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 66
IP  - 2
DP  - 2000 Feb
TI  - Reproducibility and complications in gene searches: linkage on chromosome 6, 
      heterogeneity, association, and maternal inheritance in juvenile myoclonic 
      epilepsy.
PG  - 508-16
AB  - Evidence for genetic influences in epilepsy is strong, but reports identifying 
      specific chromosomal origins of those influences conflict. One early study 
      reported that human leukocyte antigen (HLA) markers were genetically linked to 
      juvenile myoclonic epilepsy (JME); this was confirmed in a later study. Other 
      reports did not find linkage to HLA markers. One found evidence of linkage to 
      markers on chromosome 15, another to markers on chromosome 6, centromeric to HLA. 
      We identified families through a patient with JME and genotyped markers 
      throughout chromosome 6. Linkage analysis assuming equal male-female 
      recombination probabilities showed evidence for linkage (LOD score 2.5), but at a 
      high recombination fraction (theta), suggesting heterogeneity. When linkage 
      analysis was redone to allow independent male-female thetas, the LOD score was 
      significantly higher (4.2) at a male-female theta of.5,.01. Although the overall 
      pattern of LOD scores with respect to male-female theta could not be explained 
      solely by heterogeneity, the presence of heterogeneity and predominantly maternal 
      inheritance of JME might explain it. By analyzing loci between HLA-DP and HLA-DR 
      and stratifying the families on the basis of evidence for or against linkage, we 
      were able to show evidence of heterogeneity within JME and to propose a marker 
      associated with the linked form. These data also suggest that JME may be 
      predominantly maternally inherited and that the HLA-linked form is more likely to 
      occur in families of European origin.
FAU - Greenberg, D A
AU  - Greenberg DA
AD  - Mount Sinai School of Medicine, Box 1229, New York, NY 10029, USA. 
      dag@shallot.salad.mssm.edu
FAU - Durner, M
AU  - Durner M
FAU - Keddache, M
AU  - Keddache M
FAU - Shinnar, S
AU  - Shinnar S
FAU - Resor, S R
AU  - Resor SR
FAU - Moshe, S L
AU  - Moshe SL
FAU - Rosenbaum, D
AU  - Rosenbaum D
FAU - Cohen, J
AU  - Cohen J
FAU - Harden, C
AU  - Harden C
FAU - Kang, H
AU  - Kang H
FAU - Wallace, S
AU  - Wallace S
FAU - Luciano, D
AU  - Luciano D
FAU - Ballaban-Gil, K
AU  - Ballaban-Gil K
FAU - Tomasini, L
AU  - Tomasini L
FAU - Zhou, G
AU  - Zhou G
FAU - Klotz, I
AU  - Klotz I
FAU - Dicker, E
AU  - Dicker E
LA  - eng
SI  - GENBANK/AF107699
GR  - R01 NS037466/NS/NINDS NIH HHS/United States
GR  - NS27941/NS/NINDS NIH HHS/United States
GR  - R01 DK031775/DK/NIDDK NIH HHS/United States
GR  - NS37466/NS/NINDS NIH HHS/United States
GR  - DK31775/DK/NIDDK NIH HHS/United States
GR  - R01 MH048858/MH/NIMH NIH HHS/United States
GR  - R01 NS027941/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (HLA-D Antigens)
SB  - IM
MH  - Alleles
MH  - Chromosome Mapping/*methods
MH  - Chromosomes, Human, Pair 6/*genetics
MH  - Extrachromosomal Inheritance/*genetics
MH  - Fathers
MH  - Female
MH  - Gene Frequency/genetics
MH  - *Genetic Heterogeneity
MH  - HLA-D Antigens/genetics
MH  - Humans
MH  - Lod Score
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mothers
MH  - Myoclonic Epilepsy, Juvenile/*genetics
MH  - Pedigree
MH  - Recombination, Genetic/genetics
MH  - Reproducibility of Results
PMC - PMC1288104
EDAT- 2000/03/21 09:00
MHDA- 2000/04/01 09:00
PMCR- 2000/08/01
CRDT- 2000/03/21 09:00
PHST- 2000/03/21 09:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 2000/03/21 09:00 [entrez]
PHST- 2000/08/01 00:00 [pmc-release]
AID - S0002-9297(07)63425-9 [pii]
AID - 991155 [pii]
AID - 10.1086/302763 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2000 Feb;66(2):508-16. doi: 10.1086/302763.