A chromosomal duplication map of malformations: regions of suspected haplo- and triplolethality--and tolerance of segmental aneuploidy--in humans.

The distribution of simple autosomal duplications associated with congenital malformations has been analyzed by means of data contained in the Human Cytogenetics Database. For each of the 47 malformations, the frequency of duplication of a given chromosome band associated with the malformation was compared with the overall frequency of duplication of that band recorded in the database. In total, there were 143 malformation-associated chromosomal regions (MACR); 21 of these contained at least one band with a highly significant (P<.001) association. The average number of bands per MACR was 3.1. Eight bands, representing 2.1% of haploid autosomal length, were not involved in any duplication, and we suggest that these are potentially triplolethal. This compares with 31 bands, representing 11% of haploid autosomal length, that were identified in the previously reported deletion map and that were not involved in any deletion and are potentially haplolethal. In both cases, approximately half of these bands are pericentromeric. The longest duplication involves 4.3% of haploid autosomal length, and the longest deletion involves 2.7%.

[1]  S Holloway,et al.  A chromosomal deletion map of human malformations. , 1998, American journal of human genetics.

[2]  W. Reik,et al.  Imprinting of IGF2 and H19: lack of reciprocity in sporadic Beckwith-Wiedemann syndrome. , 1997, Human molecular genetics.

[3]  A. Schinzel,et al.  Human Cytogenetics Database , 1997 .

[4]  Y. Fukushima,et al.  An imprinted gene p57KIP2 is mutated in Beckwith–Wiedemann syndrome , 1996, Nature Genetics.

[5]  P. Rashbass,et al.  Influence of PAX6 Gene Dosage on Development: Overexpression Causes Severe Eye Abnormalities , 1996, Cell.

[6]  D. Ornitz,et al.  Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia , 1996, Nature Genetics.

[7]  D. Rimoin,et al.  Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I. , 1995, Human molecular genetics.

[8]  C. Bieberich,et al.  Gain of function mutations for paralogous Hox genes: implications for the evolution of Hox gene function. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[9]  A. Wilkie,et al.  The molecular basis of genetic dominance. , 1994, Journal of medical genetics.

[10]  I. Lurie.  Autosomal imbalance syndromes: genetic interactions and the origin of congenital malformations in aneuploidy syndromes. , 1993, American journal of medical genetics.

[11]  P. Jacobs,et al.  Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. , 1992, Journal of medical genetics.

[12]  C. Junien,et al.  Uniparental paternal disomy in a genetic cancer-predisposing syndrome , 1991, Nature.

[13]  J. Buehler,et al.  Overview of the National Infant Mortality Surveillance (NIMS) project. , 1989, MMWR. CDC surveillance summaries : Morbidity and mortality weekly report. CDC surveillance summaries.

[14]  K. Vasarhelyi,et al.  Analysing rearrangement breakpoint distributions by means of binomial confidence intervals , 1989, Annals of human genetics.

[15]  T. Beaty,et al.  Can familial aggregation of disease be explained by familial aggregation of environmental risk factors? , 1988, American journal of epidemiology.

[16]  C. Robinette,et al.  The study of human twins in medical research. , 1984, The New England journal of medicine.

[17]  H. Kalter,et al.  Congenital malformations (second of two parts). , 1983, The New England journal of medicine.

[18]  H. Kalter,et al.  Medical progress. Congenital malformations: etiologic factors and their role in prevention (first of two parts). , 1983 .

[19]  F. Hecht,et al.  Annotation: genetic effects of aneuploidy. , 1973, American journal of human genetics.

[20]  B. S. Baker,et al.  Segmental aneuploidy and the genetic gross structure of the Drosophila genome. , 1972, Genetics.

[21]  K. Becker,et al.  Double autosomal trisomy (D trisomy plus mongolism). , 1963, Proceedings of the staff meetings. Mayo Clinic.

[22]  A. Barbeau,et al.  [Double autosomal trisomy with 48 chromosomes (21 and 18)]. , 1961, L'union medicale du Canada.

[23]  A. Gossler,et al.  Genetic interactions suggest that Danforth's short tail (Sd) is a gain-of-function mutation. , 1998, Developmental genetics.

[24]  David I. Wilson,et al.  Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family , 1997, Nature Genetics.

[25]  J. Delabar,et al.  Molecular Mapping of Twenty-Four Features of Down Syndrome on Chromosome 21 , 1993, European journal of human genetics : EJHG.

[26]  Iscn.  International System for Human Cytogenetic Nomenclature , 1978 .

[27]  A. P. Mange,et al.  A note on the maternal effect mutants daughterless and abnormal oocyte in Drosophila melanogaster. , 1973, Genetics.

[28]  N. Myrianthopoulos,et al.  Racial and prenatal factors in major congenital malformations. , 1968, American journal of human genetics.

[29]  D. Lindsley,et al.  Genetic variations of Drosophila melanogaster , 1967 .