11q13 allelotype analysis in 27 northern American MEN1 kindreds identifies two distinct founder chromosomes.
We analyzed constitutional and tumor DNA from 27 MEN1 kindreds not known to be related to each other. Disease allele haplotypes were constructed for each pedigree based on shared alleles from two or more affected members and from determination of allelic loss patterns in their tumors. Analysis of disease allele haplotypes showed unexpected linkage disequilibrium at marker PYGM. Further haplotype analysis indicated this could be explained by the presence of two founder chromosomes, one in four families, the other in three. A shared disease haplotype was not observed among two MEN1 kindreds with the prolactinoma phenotype of MEN1.
Emmert-Buck
M R
MR
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Debelenko
L V
LV
Agarwal
S
S
Kester
M B
MB
Manickam
P
P
Zhuang
Z
Z
Guru
S C
SC
Olufemi
S E
SE
Burns
A L
AL
Chandrasekharappa
S C
SC
Lubensky
I A
IA
Liotta
L A
LA
Skarulis
M C
MC
Spiegel
A M
AM
Marx
S J
SJ
Collins
F S
FS
D000483:Alleles; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018703:Founder Effect; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009656:North America; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D005819:Genetic Markers