Identification of Transcribed Sequences

The international Human Genome Project is providing three essential ingredients for the efficient identification of diseases genes. One is the high density of polymorphic markers that are critical for the mapping of disease genes to defined chromosomal regions. The second is a physical map in the form of overlapping genomic clones in YACs or cosmids that will allow detailed analysis of the critical region. The third is a transcription map (gene map) that will provide a bank of regionally mapped candidate genes to test for mutations once a disease gene is mapped. In the past 5 years the identification and mapping of several thousand simple-sequence-repeat polymorphisms has provided the first ingredient, and the physical maps of many chromosomes are approaching completion. However, the transcription map is problematic and a long way from being a useful tool. A detailed analysis of the technology involved in building the requisite transcription maps is found in this book, the published proceedings of the third international workshop on the topic, held October 2-4, 1993, in association with the American Society of Human Genetics meeting in New Orleans.

[1]  C. Nottenburg,et al.  Lymphocyte HEV adhesion variants differ in the expression of multiple gene sequences. , 1990, Gene.

[2]  D. Church,et al.  Identification of human chromosome 9 specific genes using exon amplification. , 1993, Human molecular genetics.

[3]  J. Kirsch,et al.  Neuraxin, a novel putative structural protein of the rat central nervous system that is immunologically related to microtubule‐associated protein 5. , 1989, EMBO Journal.

[4]  M. Lovett,et al.  Magnetic bead capture of expressed sequences encoded within large genomic segments , 1993, Nature.

[5]  A. Swaroop,et al.  cDNA libraries from human tissues and cell lines. , 1993, Cytogenetics and cell genetics.

[6]  D. Easton,et al.  Allele losses in the region 17q12–21 in familial breast and ovarian cancer involve the wild–type chromosome , 1992, Nature Genetics.

[7]  R. Kaul,et al.  The deduced protein sequence of the human carboxypeptidase N high molecular weight subunit reveals the presence of leucine-rich tandem repeats. , 1990, The Journal of biological chemistry.

[8]  K. Kaibuchi,et al.  Molecular cloning of the human cDNA for a stimulatory GDP/GTP exchange protein for c-Ki-ras p21 and smg p21. , 1992, Oncogene.

[9]  S. Weissman,et al.  cDNA selection: efficient PCR approach for the selection of cDNAs encoded in large chromosomal DNA fragments. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Kley,et al.  A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. , 1993, Cell.

[11]  J. Hoch,et al.  The primary structure of the mitochondrial energy-linked nicotinamide nucleotide transhydrogenase deduced from the sequence of cDNA clones. , 1988, The Journal of biological chemistry.

[12]  L. Hood,et al.  A common language for physical mapping of the human genome. , 1989, Science.

[13]  A. Poustka,et al.  Construction of a transcription map of a 300 kb region around the human G6PD locus by direct cDNA selection. , 1993, Human molecular genetics.

[14]  D. Nelson,et al.  Direct cloning of human transcripts with HnRNA from hybrid cell lines. , 1990, Science.

[15]  J. Hofsteenge,et al.  Structure of the 55-kDa regulatory subunit of protein phosphatase 2A: evidence for a neuronal-specific isoform. , 1991, Biochemistry.

[16]  T. Sugimura,et al.  Establishment of a highly sensitive and specific exon-trapping system. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. J. Schafer,et al.  Physical mapping of human chromosome 17 using fragment-containing microcell hybrids. , 1989, Genomics.

[18]  G. Bernardi,et al.  The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  A. de la Chapelle,et al.  Localization of a gene for progressive myoclonus epilepsy to chromosome 21q22. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[20]  W. D. Benton,et al.  Screening lambdagt recombinant clones by hybridization to single plaques in situ. , 1977, Science.

[21]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[22]  R. Myers,et al.  Exon trapping: a genetic screen to identify candidate transcribed sequences in cloned mammalian genomic DNA. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[23]  B. Ponder,et al.  Structural analysis of the human ret proto-oncogene using exon trapping. , 1993, Oncogene.

[24]  P. Jong,et al.  Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy , 1992, Nature.

[25]  J. Rommens,et al.  A transcription map of the region containing the Huntington disease gene. , 1993, Human molecular genetics.

[26]  K. Kosik,et al.  The exon trapping assay partly discriminates against alternatively spliced exons. , 1993, Nucleic acids research.

[27]  H. Saito,et al.  A human transmembrane protein-tyrosine-phosphatase, PTP zeta, is expressed in brain and has an N-terminal receptor domain homologous to carbonic anhydrases. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. MacDonald,et al.  The direct screening of cosmid libraries with YAC clones. , 1991, Nucleic acids research.

[29]  S. Packman,et al.  Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper–transporting ATPase , 1993, Nature Genetics.

[30]  S. Weissman,et al.  Application of cDNA selection techniques to regions of the human MHC. , 1993, Genomics.

[31]  K. Gardiner,et al.  Analysis of chromosome 21 yeast artificial chromosome (YAC) clones. , 1992, American journal of human genetics.