Breakpoint cloning and haplotype analysis indicate a single origin of the common Inv(10)(p11.2q21.2) mutation among northern Europeans.
The pericentric inv(10)(p11.2q21.2) mutation has been frequently identified in cytogenetic laboratories, is phenotypically silent, and is considered to be a polymorphic variant. Cloning and sequencing of the junction fragments on 10p11 and 10q21 revealed that neither inversion breakpoint directly involved any genes or repetitive sequences, although both breakpoint regions contain a number of repeats. All 20 apparently unrelated inv(10) families in our study had identical breakpoints, and detailed haplotype analysis showed that the inversions were identical by descent. Thus, although considered a common variant, inv(10)(p11.2q21.2) has a single ancestral founder among northern Europeans.
Gilling
Mette
M
Wilhelm Johannsen Center for Functional Genome Research, University of Copenhagen, Copenhagen.
Dullinger
Jörn S
JS
Max Planck Institute for Molecular Genetics, Berlin, Germany; Charité University Hospital, Berlin, Germany.
Gesk
Stefan
S
Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Metzke-Heidemann
Simone
S
Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Siebert
Reiner
R
Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Meyer
Thomas
T
Charité University Hospital, Berlin, Germany.
Brondum-Nielsen
Karen
K
The John F. Kennedy Institute, Glostrup, Denmark.
Tommerup
Niels
N
Wilhelm Johannsen Center for Functional Genome Research, University of Copenhagen, Copenhagen.
Ropers
Hans-Hilger
HH
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Tümer
Zeynep
Z
Wilhelm Johannsen Center for Functional Genome Research, University of Copenhagen, Copenhagen.
Kalscheuer
Vera M
VM
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Thomas
N Simon
NS
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom. Electronic address: simon.thomas@salisbury.nhs.uk.
D001483:Base Sequence; D002503:Centromere; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D002879:Chromosomes, Human, Pair 10; D003001:Cloning, Molecular; D015331:Cohort Studies; D005060:Europe; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide