Genomics of human dysmorphogenesis.
A survey of Mendelian Inheritance in Man emphasizes the large Mendelian contribution to human dysmorphogenesis and contrasts single gene conditions with chromosomal disorders. There were 1761 conditions that involved altered morphogenesis (49% of disease entries), including 1040 multiple defect syndromes and 721 inherited single birth defects. Premature death (36-57%), mental retardation (20-59%), and growth retardation (37-59%) are more frequent in autosomal recessive or X-linked syndromes, while predisposition to tumorigenesis was more common in dominant (16%) than recessive (3.4%) syndromes. Comparison of the Mendelian conditions with 100 chromosomal disorders showed a strikingly similar spectrum of malformation, with skeletal, craniofacial, eye, epidermal, and neuromuscular systems being most frequently affected. Chromosomal syndromes average 10.6 systems affected per disorder, in contrast to 3.55 for Mendelian syndromes, and pleiotropy does correlate weakly with aneuploid segment length. Genomic understanding of these relationships is still primitive, with 74 of 1609 (4.6%) autosomal conditions and 43 of 152 (29%) X-linked conditions mapped to specific chromosomal regions. The societal toll of human dysmorphogenesis and the evident progress with X-linked disorders provide a powerful rationale for the Human Genome Project.
Wilson
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GN
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
D002869:Chromosome Aberrations / Q000235:genetics* / Q000473:pathology; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D000013:Congenital Abnormalities / Q000235:genetics*; D006801:Humans; D009024:Morphogenesis / Q000235:genetics*; D010641:Phenotype; D013223:Statistics as Topic; D013577:Syndrome