Inherited Disease Genes Identified by Positional Cloning

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The table below was compiled by the staff of the National Center for Biotechnology Information. This list contains many of the early genes that were cloned by positional cloning. Many additional genes have also been discovered using this technique. I would like to the thank the staff of NCBI, in particular Tyra Wolfsberg and John Pearson, for making this site available.

Low-Complexity Segments Possible Non-Globular Regions
Disease Gene Symbol Year Accession Number OMIM Number Number Percent Number Percent
Aarskog-Scott Syndrome FGD1 1994 U11690 305400 10 16.8% 1 38.2%
Achondroplasia FGFLR 1994 M64347 100800 4 8.3% 2 23.3%
Adenomatous Polyposis Coli APC 1991 M74088 175100 27 15.4% 10 62.9%
Adrenoleukodystrophy, X-linked ALD 1993 Z21876 300100 3 6.7% 3 40.7%
Agammaglobulinemia, X-linked BTK 1993 U78027 300300 3 5.4% 1 6.8%
Alagille Syndrome AGS 1997 X83384 118450        
Alzheimer Disease (Chromosome 14) AD3 1995 L42110 104311 4 14.1% 3 42.6%
Alzheimer Disease (Chromosome 1) AD4 1995 L44577 600759 3 13.4% 1 27.5%
Amyotrophic Lateral Sclerosis SOD1 1991 K00065 105400 0 0.0% 0 0.0%
Angelman Syndrome AS 1997 U84404 105830 3 6.2% 2 22.7%
Anhidrotic Ectodermal Dysplasia EDA 1996 U59228 305100 1 57.7% 1 95.5%
Aniridia PAX6 1991 M77844 106210 5 14.2% 2 59.7%
Ataxia Telangiectasia ATM 1995 U26455 208900 1 0.9% 3 13.9%
Barth Syndrome BTHS 1996 X92762 302060 0 0.0% 0 0.0%
Basal Cell Nevus Syndrome BCNS 1996 U59464 109400 10 11.6% 5 58.6%
Best Macular Dystrophy BMD 1998 157300        
Bloom Syndrome BLM 1995 U39817 210900 9 11.2% 3 25.3%
Breast Cancer, Type 1 BRCA1 1994 U14680 113705 9 6.3% 5 32.6%
Breast Cancer, Type 2 BRCA2 1995 U43746 600185 7 2.9% 4 8.5%
Chedial-Higashi Syndrome CHS 1996 U78038 214500        
Choroideremia CHM 1990 X78121 303100 1 2.6% 2 27.6%
Chondrodysplasia Punctata ARSE 1994 X83573 302950 4 11.2% 2 19.7%
Chronic Granulomatous Disease NCF1 1986 M55067 233700 1 3.3% 2 40.3%
Congenital Adrenal Hyperplasia CYP21 1994 M26856 201910 2 8.6% 1 19.4%
Congenital Nephrotic Syndrome NPHS1 1998 AF035835 256300        
Congenital Night Blindness, X-Linked CSNB 1998 310500        
Cystic Fibrosis CFTR 1989 M28668 219700 3 3.4% 2 12.2%
Cystinosis CTNS 1998 AJ222967 219800        
Deafness DFNA1 1997   124900        
Deafness DFNA5 1998   600994        
Dementia, Hereditary Multi-infarct CADASIL 1996   125310        
Denatorubral Pallidoluysian Atrophy DRPLA 1994 L10379 125370        
Diabetes of the young, Maturity-Onset MODY3 1996 G29084 600496        
Diastrophic Dysplasia DTD 1994 U14528 222600 5 11.0% 2 19.5%
Duchenne Muscular Dystrophy DMD 1986 M18533 310200 13 6.4% 13 44.1%
Dystonia GCH1 1997   128230        
Emery-Dreifuss Muscular Dystrophy STA 1994 X82434 310300 3 20.9% 1 37.8%
Epidermolytic Palmoplantar Keratoderma KRT9 1993 X75015 144200 3 48.4% 3 63.3%
Familial Mediterranean Fever MEFV 1997 AF018080 249100 1 1.5% 1 54.8%
Fanconi Anemia A FAA 1996 L02651 227650 2 4.3% 1 20.1%
Fragile-X Syndrome FMR1 1991 S65791 309550 2 5.4% 1 22.8%
Friedreich Ataxia FRDA 1996 U60871 229300 0 0.0% 0 0.0%
Fukuyama-type Congenital Muscular Dystrophy FCMD 1998 AB008226 253800 1 3.5% 0 0.0%
Glycerol Kinase Deficiency GK 1993 L13943 307030 0 0.0% 0 0.0%
Gonadal Dysgenesis SRY 1990 L08063 480000 0 0.0% 0 0.0%
Hemochromatosis HFE 1996 U26556 235200        
Hereditary Multiple Exostoses, Type 1 EXT1 1995 S79639 133700 2 3.5% 0 0.0%
Hereditary Multiple Exostoses, Type 2 EXT2 1995 U94835 133701 2 4.0% 2 18.9%
Hereditary Non-Polyposis Colon Cancer MLH1   U07343 120436 2 3.2% 1 10.2%
Hereditary Non-Polyposis Colon Cancer MSH2   U03911 120435 2 2.5% 1 9.0%
Hermansky-Pudlak Syndrome HPS 1996 U04055 203300 1 2.4% 0 0.0%
Holt-Oram Syndrome HOS 1997 Y09445 142900 3 7.9% 1 28.6%
Huntington Disease HD 1993 L12392 143100 13 7.4% 6 22.6%
Hyperexplexia GLYRA2   X52009 149400 4 12.5% 0 0.0%
Hypophosphatemic Rickets XLH 1995 U49908 307800 1 2.1% 0 0.0%
Juvenile Glaucoma GLC1A 1997 AF001620 137750        
Kallman Syndrome KAL 1991 M97252 308700 3 7.5% 1 8.1%
Lafora disease MELF 1998   254780        
Limb-Girdle Muscular Dystrophy LGMD2A 1995 U29586 253600 2 6.2% 1 9.1%
Limb-Girdle Muscular Dystrophy Type 2B LGMD2B 1998 AJ007670 253601 2 1.3% 2 11.5%
Lissencephaly, X-Linked LISX 1998   300067        
Long QT Syndrome LQT1 1996 U40990 192500 3 10.1% 0 0.0%
Lowe Oculocerebrorenal Syndrome OCRL 1992 M88162 309000 1 1.2% 1 12.2%
Machado-Joseph Disease MJD1 1994 S75313 109150 1 7.2% 1 36.7%
McLeod Syndrome XK 1994 Z32684 314850 2 7.9% 2 36.7%
Menkes Disease MNK 1993 X69208 309400 1 2.4% 1 20.1%
Miller-Dieker Lissencephaly PAF 1993 L13385 247200 0 0.0% 0 0.0%
Multiple Endocrine Neoplasia, Type 1 MEN1 1997 U93237 131100 5 14.6% 3 58.5%
Multiple Endocrine Neoplasia, Type 2a RET   M57464 171400 2 2.9% 1 7.6%
Myotonic Dystrophy DM 1992 L19268 160900 4 13.5% 3 61.4%
Myotubular Myopathy 1, X-linked MTM1 1996 U58034 310400 1 21.6% 0 0.0%
Neurofibromatosis, Type 1 NF1 1990 M89914 162200 3 1.3% 1 2.5%
Neurofibromatosis, Type 2 NF2 1993 L11353 101000 3 8.1% 2 44.0%
Neuronal Ceroid-Lipofuscinosis, Late Infantile CLN2 1998 204500        
Niemann-Pick Disease, Type C NPC1 1997 AF002020 257220 3 2.7% 3 23.0%
Nijmegen Breakage Syndrome NBS1 1998 602667        
Norrie Disease NDP 1992 X65882 310600 0 0.0% 0 0.0%
Obesity OBS   U18915 164160 0 0.0% 1 40.7%
Ocular Albinism OA1 1995 Z48804 300500 3 15.3% 1 24.1%
Oculopharyngeal Muscular Dystrophy OPMD 1998   300000        
Opitz Syndrome OS 1997   164300        
Pendred Syndrome PDS 1997   274600        
Peutz-Jeghers Syndrome PJS 1998 AF032984 175200        
Polycystic Kidney Disease, Type 1 PKD1 1994 L33243 173900 14 16.0% 4 69.4%
Polycystic Kidney Disease, Type 2 PKD2 1996 U50928 173910 12 24.3% 2 46.3%
Progressive Myoclonic Epilepsy PME 1996 U46692 254800 0 0.0% 0 0.0%
Retinitis Pigmentosa, X-linked RP3 1996 X97668 312610 5 8.0% 1 21.3%
Retinitis Pigmentosa 2, X-linked RP2 1998 AJ007590 312600 0 0% 0 0%
Retinoblastoma RB1 1986 M15400 180200 1 3.2% 2 7.9%
Rieger Syndrome, Type 1 RIEG1 1996 U70132 180500 3 23.9% 1 52.5%
Simpson-Golabi-Behmel Syndrome SDYS 1996 L47125 312870 2 5.1% 0 0.0%
Situs Inversus HTX1 1997 D70849 306955 4 10.7% 2 62.4%
Spinal Muscular Atrophy SMA 1995 U18423 253300 4 37.4% 1 32.3%
Spinocerebellar Ataxia 1 SCA1 1993 X79204 164400 6 13.2% 4 72.7%
Spinocerebellar Ataxia 2 SCA2 1996 U70323 183090 17 30.4% 4 83.4%
Spinocerebellar Ataxia 7 SCA7 1997   164500        
Stargardt's Disease STGD1 1997 U88667 248200 9 5.2% 2 6.8%
Thomsen Disease CLC1   Z25884 160800 7 9.8% 3 37.1%
Treacher Collins Syndrome TCS 1996 U81030 154500 27 39.4% 1 95.8%
Tuberous Sclerosis TSC 1993 X75621 191090 9 8.2% 4 31.3%
Tuberous Sclerosis 1 TSC1 1997 D87438 191100 2 3.0% 1 10.9%
von Hippel-Lindau Syndrome VHL 1993 L15409 193300 2 20.4% 0 0.0%
Waardenburg Syndrome PAX3   U02309 268200 0 0.0% 1 51.8%
Werner Syndrome WRN 1996 S69873 277700        
Wilms Tumor WT1 1990 X51630 194070 4 12.9% 1 40.3%
Wilson Disease WND 1993 L25591 277900 0 0.0% 0 0.0%
Wiskott-Aldrich Syndrome WASP 1994 U12707 301000 6 8.7% 2 60.4%
Wolfram Syndrome WFS 1998   222300        

In the Low-Complexity Segments and Possible Non-Globular Regions columns, the first number represents the number of segments or regions, while the second indicates what percentage of the protein (amino acids) are found in those regions. Low-complexity segments are compositionally biased regions which include different types of near-homopolymeric residue clusters, short-period repeats, and aperiodic mosaics of only a few residue types (Wootton, 1994).