title: Systematic genome-wide approach to positional candidate cloning for identification of novel human disease genes.
abstract: BACKGROUND
  Recent large-scale genome projects afford a unique opportunity to identify many novel disease genes and thereby better understand the genetic basis of human disease. Functional Annotation of Mouse (FANTOM) 2, the largest mouse transcriptome project yet, provides a wealth of data on novel genes, splice variants and non-coding RNA, and provides a unique opportunity to identify novel human disease genes.
  
  
  OBJECTIVE
  To demonstrate the power of combining the FANTOM 2 cDNA dataset with a positional candidate approach and bioinformatics analysis to identify genes underlying human genetic disease.
  
  
  RESULTS
  By mapping all FANTOM 2 cDNA to the human genome, we were able to identify mouse clones that co-localised on the human genome with mapped but uncloned human disease loci. By this method we identified mouse and corresponding human genes mapping within the loci of 100 different human genetic diseases (mapped interval of <5 cM). Of particular interest was the elucidation through FANTOM 2 novel mouse gene data of candidate human genes for the following: (i) developmental -disorders: neural tube defect, Meckel syndrome, Wolf--Hirschhorn syndrome and keratosis follicularis spinulosa decalvans cum ophiasi; (ii) neurological disorders: benign familial infantile convulsions 3, early-onset cerebellar ataxia with retained tendon reflexes, infantile-onset spinocerebellar ataxia and vacuolar neuro-myopathy and (iii) cancer-related syndromes: tylosis with oesophageal cancer and low-grade B-cell chronic lymphatic leukaemia.
  
  
  CONCLUSIONS
  The FANTOM 2 data will dramatically accelerate efforts to identify genes underlying human disease. It will also facilitate the creation of transgenic mouse models to help elucidate the function of potential human disease genes.
authors.affiliation: Technology and Development team for Mammalian Cellular Dynamics, Bioresource Center, RIKEN Tsukuba Institute, Tsukuba, Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kiyosawa
authors.forename: T
authors.initials: T
authors.lastname: Kawashima
authors.forename: D
authors.initials: D
authors.lastname: Silva
authors.forename: N
authors.initials: N
authors.lastname: Petrovsky
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashizaki
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003001:Cloning, Molecular; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics*; D007644:Darier Disease / Q000235:genetics; D030541:Databases, Genetic; D030561:Databases, Nucleic Acid; D020936:Epilepsy, Benign Neonatal / Q000235:genetics; D015723:Gene Library; D015894:Genome, Human; D015698:Genomic Library; D023281:Genomics; D006801:Humans; D051379:Mice / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D013132:Spinocerebellar Degenerations / Q000235:genetics
chemical_list: D018076:DNA, Complementary