Mapping of a single locus capable of complementing the defective heterochromatin phenotype of Roberts syndrome cells.
Roberts syndrome (RS) is a developmental disorder characterized by tetraphocomelia and a broad spectrum of additional clinical features. Most patients with RS exhibit characteristic cytogenetic phenotypes, which include an abnormal appearance of pericentromeric heterochromatin on metaphase chromosomes, referred to as "heterochromatic repulsion." In the present study, we use complementation of this abnormal cytogenetic phenotype as a means to identify a specific region of the normal human genome capable of rendering phenotypic correction. We screened the entire human genome, using a transient chromosome-transfer assay, and demonstrated complementation exclusively after the transfer of proximal chromosome 8p, a result subsequently confirmed by stable microcell-mediated chromosome transfer. Additionally, homozygosity mapping was used to refine the interval of this complementing locus to 8p21. The results are consistent with the notion that the single gene defect responsible for heterochromatic splaying and developmental abnormalities maps to chromosome 8p21.
McDaniel
Lisa D
LD
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9072, USA. lisa.mcdaniel@utsouthwestern.edu
Tomkins
Darrell J
DJ
Stanbridge
Eric J
EJ
Somerville
Martin J
MJ
Friedberg
Errol C
EC
Schultz
Roger A
RA
D000015:Abnormalities, Multiple / Q000235:genetics*; D001848:Bone Diseases, Developmental / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D019465:Craniofacial Abnormalities; D005816:Genetic Complementation Test; D006570:Heterochromatin / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D010641:Phenotype; D013577:Syndrome
D006570:Heterochromatin