Beyond Mendel: an evolving view of human genetic disease transmission (original) (raw)
Scriver, C. R. & Waters, P. J. Monogenic traits are not simple: lessons from phenylketonuria. Trends Genet.15, 267–272 (1999). ArticleCASPubMed Google Scholar
Dipple, K. M. & McCabe, E. R. B. Phenotypes of patients with 'simple' Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. Am. J. Hum. Genet.66, 1729–1735 (2000).Illustrates the increasing levels of complexity that are seen in 'simple' Mendelian disorders and presents thresholds models to correlate mutations with phenotypes. ArticleCASPubMedPubMed Central Google Scholar
Dipple, K. M. & McCabe, E. R. B. Modifier genes convert 'simple' Mendelian disorders to complex traits. Mol. Genet. Metab.71, 43–50 (2000). ArticleCASPubMed Google Scholar
Weiss, K. M. Is there a paradigm shift in genetics? Lessons from the study of human diseases. Mol. Phylogenet. Evol.5, 259–265 (1996). ArticleCASPubMed Google Scholar
Jervis, G. A. Phenylpyruvic oligophrenia deficiency of phenylalanine-oxidizing system. Proc. Soc. Exp. Biol. Med.82, 514–515 (1953). CASPubMed Google Scholar
Guthrie, R. & Susi, A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics32, 338–343 (1963). CASPubMed Google Scholar
Guthrie, R. The introduction of newborn screening for phenylketonuria: a personal history. Eur. J. Pediat.155, 4–5 (1996). Article Google Scholar
Scriver, C. R. Whatever happened to PKU? Clin. Biochem.28, 137–144 (1995). Comprehensive revision of phenylketonuria and its history, as well as a useful discussion of the complex genetics of this disorder. ArticleCASPubMed Google Scholar
Woo, S. L. C., Lidsky, A. S., Guttler, F., Chandra, D. & Robson, K. J. H. Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature306, 151–155 (1983). ArticleCASPubMed Google Scholar
Blau, N., Thony, B., Heizmann, C. W. & Dhondt, J.-L. Tetrahydrobiopterin deficiency: from phenotype to genotype. Pteridines4, 1–10 (1993). ArticleCAS Google Scholar
Enns, G. M. et al. Molecular correlations in phenylketonuria: mutation patterns and corresponding biochemical and clinical phenotypes in a heterogeneous California population. Pedriatr. Res.46, 594–602 (1999). ArticleCAS Google Scholar
Tsui, L. C. et al. Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science230, 1054–1057 (1985). ArticleCASPubMed Google Scholar
Riordan, J. R. et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science245, 1066–1073 (1989). ArticleCASPubMed Google Scholar
Acton, J. D. & Wilmott, R. W. Phenotype of CF and the effects of possible modifier genes. Pediatr. Respir. Rev.2, 332–339 (2001). CAS Google Scholar
Drumm, M. L. Modifier genes and variation in cystic fibrosis. Resp. Res.2, 125–128 (2001). ArticleCAS Google Scholar
Mickle, J. E. & Cutting, G. R. Genotype–phenotype relationships in cystic fibrosis. Med. Clin. N. Am.84, 597–607 (2000). ArticleCASPubMed Google Scholar
Nadeau, J. H. Modifier genes in mice and humans. Nature Rev. Genet.2, 165–174 (2001).An elegant and comprehensive discussion of modifier genes and the lessons that can be learned from studying mouse models of human disease. ArticleCASPubMed Google Scholar
Zielenski, J. et al. Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13. Nature Genet.22, 128–129 (1999). ArticleCASPubMed Google Scholar
Rozmahel, R. et al. Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nature Genet.12, 280–287 (1996). ArticleCASPubMed Google Scholar
Arkwright, P. D. et al. TGF-β(1) genotype and accelerated decline in lung function of patients with cystic fibrosis. Thorax55, 459–462 (2000). ArticleCASPubMedPubMed Central Google Scholar
Hull, J. & Thomson, A. H. Contribution of genetic factors other than CFTR to disease severity in cystic fibrosis. Thorax53, 1018–1021 (1998). ArticleCASPubMedPubMed Central Google Scholar
Aron, Y. et al. HLA class II polymorphism in cystic fibrosis. A possible modifier of pulmonary phenotype. Am. J. Respir. Crit. Care Med.159, 1464–1468 (1999). ArticleCASPubMed Google Scholar
Garred, P. et al. Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J. Clin. Invest.104, 431–437 (1999). ArticleCASPubMedPubMed Central Google Scholar
Grasemann, H. et al. Airway nitric oxide levels in cystic fibrosis patients are related to a polymorphism in the neuronal nitric oxide synthase gene. Am. J. Respir. Crit. Care Med.162, 2172–2176 (2000). ArticleCASPubMed Google Scholar
Parmley, R. R. & Gendler, S. J. Cystic fibrosis mice lacking Muc1 have reduced amounts of intestinal mucus. J. Clin. Invest.102, 1798–1806 (1998). ArticleCASPubMedPubMed Central Google Scholar
Wang, X. et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA284, 1814–1819 (2000). ArticleCASPubMed Google Scholar
Groman, J. D., Meyer, M. E., Wilmott, R. W., Zeitlin, P. L. & Cutting, G. R. Variant cystic fibrosis phenotypes in the absence of CFTR mutations. N. Engl. J. Med.347, 401–407 (2002). ArticleCASPubMed Google Scholar
Polanyi, M. Life's irreducible structure. Live mechanisms and information in DNA are boundary conditions with a sequence of boundaries above them. Science160, 53–91 (1968). Article Google Scholar
Strohman, R. Maneuvering in the complex path from genotype to phenotype. Science296, 701–703 (2002). ArticleCASPubMed Google Scholar
Sawa, A. & Snyder, S. H. Schizophrenia: diverse approaches to a complex disease. Science296, 692–695 (2002). An in-depth review of approaches to studying the pathogenesis of schizophrenia. ArticleCASPubMed Google Scholar
Hand, C. K. & Rouleau, G. A. Familial amyotrophic lateral scloerosis. Muscle Nerve25, 135–159 (2002). ArticleCASPubMed Google Scholar
Giess, R. et al. Early onset of severe familial amyotrophic lateral sclerosis with a _SOD_-1 mutation: potential impact of CNTF as a candidate modifier gene. Am. J. Hum. Genet. 70, 1277–1286 (2002).Description of how, in an ALS patient,CNTFmodulates the severity of aSOD1mutation. ArticleCASPubMedPubMed Central Google Scholar
Takahashi, R. et al. A null mutation in the human CNTF gene is not causally related to neurological diseases. Nature Genet.7, 79–84 (1994). ArticleCASPubMed Google Scholar
Su, L. K. et al. A germ line mutation of the murine homolog of the APC gene causes multiple intestinal neoplasia. Science256, 668–670 (1992). ArticleCASPubMed Google Scholar
Moser, A. R., Dove, W. F., Roth, K. A. & Gordon, J. I. The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. J. Cell Biol.116, 1517–1526 (1992). ArticleCASPubMed Google Scholar
Moser, A. R., Pitot, H. C. & Dove, W. F. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science247, 322–324 (1990). ArticleCASPubMed Google Scholar
Dietrich, W. F. et al. Genetic identification of Mom-1, a major modifier locus affecting _Min_-induced intestinal neoplasia in the mouse. Cell75, 631–639 (1993). ArticleCASPubMed Google Scholar
Coleman, D. L. & Eicher, E. M. Fat (fat) and Tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J. Hered.81, 424–427 (1990). ArticleCASPubMed Google Scholar
Noben-Trauth, K., Naggert, J. K., North, M. A. & Nishina, P. M. A candidate gene for the mouse mutation tubby. Nature380, 534–538 (1996). ArticleCASPubMed Google Scholar
Kleyn, P. W. et al. Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family. Cell85, 281–290 (1996). ArticleCASPubMed Google Scholar
Ikeda, A. et al. Genetic modification of hearing in tubby mice: evidence for the existence of a major gene (Moth1) which protects tubby mice from hearing loss. Hum. Mol. Genet.8, 1761–1767 (1999). ArticleCASPubMed Google Scholar
Ikeda, A. et al. Microtubule-associated protein 1A is a modifier of tubby hearing (moth1). Nature Genet.30, 401–405 (2002). Cloning of the genetic modifier oftubbyand the demonstration, through the use of transgenic animals, that sequence polymorphisms inMap1aare responsible for protection against the hearing defect oftubbymutant mice. ArticleCASPubMed Google Scholar
Kajiwara, K., Berson, E. L. & Dryja, T. P. Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science264, 1604–1608 (1994). Shows that heterozygous mutations in two distinct genes are necessary and sufficient to cause RP in some patients. Probably the first example of digenic mutations in humans. ArticleCASPubMed Google Scholar
Rivolta, C., Sharon, D., DeAngelis, M. M. & Dryja, T. P. Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns. Hum. Mol. Genet.11, 1219–1227 (2002). ArticleCASPubMed Google Scholar
Katsanis, N. et al. Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet–Biedl syndrome. Nature Genet.26, 67–70 (2000). ArticleCASPubMed Google Scholar
Slavotinek, A. M. et al. Mutations in MKKS cause Bardet–Biedl syndrome. Nature Genet.26, 15–16 (2000). ArticleCASPubMed Google Scholar
Beales, P. L. et al. Genetic and mutational analyses of a large multiethnic Bardet–Biedl cohort reveal a minor involvement of BBS6 and delineate the critical intervals of other loci. Am. J. Hum. Genet.68, 606–616 (2001). ArticleCASPubMedPubMed Central Google Scholar
Nishimura, D. Y. et al. Positional cloning of a novel gene on chromosome 16q causing Bardet–Biedl syndrome (BBS2). Hum. Mol. Genet.10, 865–874 (2001). ArticleCASPubMed Google Scholar
Katsanis, N. et al. Triallelic inheritance in Bardet–Biedl syndrome, a Mendelian recessive disorder. Science293, 2256–2259 (2001). First example of triallelic inheritance in humans, in a disease considered historically to be an autosomal-recessive trait. ArticleCASPubMed Google Scholar
Moore, J. H. & Williams, S. M. New strategies for identifying gene-gene interactions in hypertension. Ann. Med.34, 88–95 (2002). ArticleCASPubMed Google Scholar
McCallion, A. S. & Chakravarti, A. in Inborn Errors of Development (eds Epstein, C., Erickson, R. & Wynshaw-Boris, A. (Oxford Univ. Press, San Francisco, in the press).
Puffenberger, E. G. et al. A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. Cell79, 1257–1266 (1994). ArticleCASPubMed Google Scholar
Parisi, M. A. & Kapur, R. P. Genetics of Hirschsprung disease. Curr. Opin. Pediatr.12, 610–617 (2000). ArticleCASPubMed Google Scholar
Angrist, M. et al. A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10. Nature Genet.3, 351–356 (1993). Article Google Scholar
Lyonnet, S. et al. A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10. Nature Genet.4, 346–350 (1993). ArticleCASPubMed Google Scholar
Bolk-Gabriel, S. B. et al. Segregation at three loci explains familial and population risk in Hirschsprung disease. Nature Genet.31, 89–93 (2002). ArticleCAS Google Scholar
Bolk, S. et al. A human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus. Proc. Natl Acad. Sci. USA97, 268–273 (2000). References59and60establish statistical methods to analyse the documented oligogenicity of Hirschsprung disease. ArticleCASPubMedPubMed Central Google Scholar
Floeth, M. & Bruckner-Tuderman, L. Digenic junctional epidermolysis bullosa: mutations in COL17A1 and LAMB3 genes. Am. J. Hum. Genet.65, 1530–1537 (1999). ArticleCASPubMedPubMed Central Google Scholar
Kestila, M. et al. Positionally cloned gene for a novel glomerular protein nephrin is mutated in congenital nephrotic syndrome. Mol. Cell1, 575–582 (1998). ArticleCASPubMed Google Scholar
Patrakka, J. et al. Congenital nephrotic syndrome (NPHS1): features resulting from different mutations in Finnish patients. Kidney Int.58, 972–980 (2000). ArticleCASPubMed Google Scholar
Boute, N. et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nature Genet.24, 349–354 (2000). ArticleCASPubMed Google Scholar
Huber, T. B., Kottgen, M., Schilling, B., Walz, G. & Benzing, T. Interaction with podocin facilitates nephrin signaling. J. Biol. Chem.276, 1543–1546 (2001). Google Scholar
Koziell, A. et al. Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration. Hum. Mol. Genet.11, 379–388 (2002). ArticleCASPubMed Google Scholar
Mykytyn, K. et al. Identification of the gene that, when mutated, causes the human obesity syndrome BBS4. Nature Genet.28, 188–191 (2001). ArticleCASPubMed Google Scholar
Katsanis, N. et al. BBS4 is a minor contributor to Bardet–Biedl syndrome and may also participate in triallelic inheritance. Am. J. Hum. Genet.71, 22–29 (2002). ArticleCASPubMedPubMed Central Google Scholar
Stone, E. M. et al. Identification of a gene that causes primary open angle glaucoma. Science275, 668–670 (1997). ArticleCASPubMed Google Scholar
Stoilov, I., Akarsu, A. N. & Sarfarazi, M. Identification of three different truncating mutations in cytochrome P450B1 (CYP1B1) as the principal cause of primary congenital glaucoma (buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum. Mol. Genet.6, 641–647 (1997). ArticleCASPubMed Google Scholar
Fingert, J. H. et al. Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Hum. Mol. Genet.8, 899–905 (1999). ArticleCASPubMed Google Scholar
Bejjani, B. A. et al. Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus. Hum. Mol. Genet.12, 367–374 (2000). Article Google Scholar
Bejjani, B. A. et al. Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia. Am. J. Hum. Genet.62, 325–333 (1998). ArticleCASPubMedPubMed Central Google Scholar
Vincent, A. L. et al. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Am. J. Hum. Genet.70, 448–460 (2002). ArticleCASPubMedPubMed Central Google Scholar
Hanna, I. H., Dawling, S., Roodi, N., Guengerich, F. P. & Parl, F. F. Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with functional differences in hydrogen hydroxylation activity. Cancer Res.60, 3440–3444 (2000). CASPubMed Google Scholar
Shimada, T., Watanabe, J., Inoue, K., Guengerich, F. P. & Gillam, E. M. Specificity of 17b-oestradiol and benzo[a]pyrene oxidation by polymorphic human cytochrome P450B1 variants substituted at residues 48, 119 and 432. Xenobiotica31, 163–176 (2001). ArticleCASPubMed Google Scholar
Shimada, T. et al. Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis20, 1607–1613 (1999). ArticleCASPubMed Google Scholar
Li, D. N., Seidel, A., Pritchard, M. P., Wolf, C. R. & Friedberg, T. Polymorphisms in P450 CYP1B1 affect the conversion of estradiol to the potentially carcinogenic metabolite 4-hydroxyestradiol. Pharmacogenetics10, 343–353 (2000). ArticleCASPubMed Google Scholar
Goldberg, A. F. X. & Molday, R. S. Subunit composition of the peripherin/rds-rom-1 disk rim complex from rod photoreceptors: hydrodynamic evidence for a tetrameric quaternary structure. Biochemistry35, 6144–6149 (1996). ArticleCASPubMed Google Scholar
Clark, G. et al. Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis. Nature Genet.25, 67–73 (2000). ArticleCAS Google Scholar
Travis, G. H., Brennan, M. B., Danielson, P. E., Kozak, C. A. & Sutcliffe, J. G. Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds). Nature338, 70–73 (1989). ArticleCASPubMed Google Scholar
Loewen, C. J., Moritz, O. L. & Molday, R. S. Molecular characterization of the peripherin-2 and rom-1 mutants responsible for digenic retinitis pigmentosa. J. Biol. Chem.276, 22388–22396 (2001). ArticleCASPubMed Google Scholar
Goldberg, A. F. & Molday, R. S. Defective subunit assembly underlies a digenic form of retinitis pigmentosa linked to mutations in peripherin/rds and rom-1. Proc. Natl Acad. Sci. USA93, 13726–13730 (1996). References82and83illustrate the molecular basis of digenic inheritance involvingROM1andRDSin human RP. ArticleCASPubMedPubMed Central Google Scholar
Schwartz, K. et al. Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J. Clin. Invest.108, 1621–1629 (2001). Article Google Scholar
Angrist, M., Bolk, S., Halushka, M., Lapchak, P. & Chakravarti, A. Germline mutations in glial cell-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient. Nature Genet.14, 341–344 (1996). ArticleCASPubMed Google Scholar
Durbec, P. et al. GDNF signaling through the Ret receptor tyrosine kinase. Nature381, 789–793 (1996). ArticleCASPubMed Google Scholar
Treanor, J. J. et al. Characterization of a multicomponent receptor for GDNF. Nature382, 80–83 (1996). ArticleCASPubMed Google Scholar
Li, L. et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nature Genet.16, 243–251 (1997). ArticleCASPubMed Google Scholar
Oda, T. et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nature Genet.16, 235–242 (1997). ArticleCASPubMed Google Scholar
McCright, B., Lozier, J. & Gridley, T. A mouse model for Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency. Development129, 1075–1082 (2002). Describes the molecular basis of phenotypic modification of theJag1mutation. CASPubMed Google Scholar
Yook, K. J., Proulx, S. R. & Jorgensen, E. M. Rules of nonallelic complementation at the synapse in Caenorhabditis elegans. Genetics158, 209–220 (2001). A comprehensive analysis of non-allelic non-complementation and establishment of its parameters of action in the worm synapse. CASPubMedPubMed Central Google Scholar
Fuller, M. T. et al. Interacting genes identify interacting proteins involved in microtubule function in Drosophila. Cell Motil. Cytoskeleton14, 128–135 (1989). ArticleCASPubMed Google Scholar
Stearns, T. & Botstein, D. Unlinked noncomplementation: isolation of new conditional-lethal mutations in each of the tubulin genes of Saccharomyces cerevisiae. Genetics119, 249–260 (1988). A classic paper on the use of non-allelic non-complementation to study specific signalling pathways. CASPubMedPubMed Central Google Scholar
Westphal, I. V. et al. A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency. Hum. Mol. Genet.11, 599–604 (2002). ArticleCASPubMed Google Scholar
Gavin, A. C. et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature415, 41–47 (2002). Article Google Scholar
Ho, Y. et al. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature415, 180–183 (2002). ArticleCASPubMed Google Scholar
Scriver, C. R. Why mutation analysis does not always predict clinical consequences: explanations in the era of genomics. J. Pediatr.140, 502–506 (2002). ArticlePubMed Google Scholar
Allikmets, R. et al. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science277, 1805–1807 (1997). ArticleCASPubMed Google Scholar
Allikmets, R. et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nature Genet.15, 236–246 (1997). ArticleCASPubMed Google Scholar
Sun, H., Smallwood, P. M. & Nathans, J. Biochemical defects in ABCR protein variants associated with human retinopathies. Nature Genet.26, 242–246 (2000). ArticleCASPubMed Google Scholar
Shroyer, N. F., Lewis, R. A., Yatsenko, A. N., Wensel, T. G. & Lupski, J. R. Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration. Hum. Mol. Genet.10, 2671–2678 (2001). References100and101show the mutagenic potential of alleles for which pathogenicity had been disputed according to genetic criteria. ArticleCASPubMed Google Scholar
del Castillo, I. et al. A deletion involving the connexin 30 gene in nonsyndromic hearing impairment. N. Engl. J. Med.346, 243–249 (2002). ArticleCASPubMed Google Scholar
Riazuddin, S. et al. Dominant modifier DFNM1 suppresses recessive deafness DFNB26. Nature Genet.26, 431–434 (2000). ArticleCASPubMed Google Scholar
Adato, A. et al. Possible interaction between USH1B and USH3 gene products as implied by apparent digenic deafness inheritance. Am. J. Hum. Genet.65, 261–265 (1999). ArticleCASPubMedPubMed Central Google Scholar
Balciuniene, J. et al. Evidence for digenic inheritance of nonsyndromic hereditary hearing loss in a Swedish family. Am. J. Hum. Genet.63, 786–793 (1998). ArticleCASPubMedPubMed Central Google Scholar
Morell, R. et al. Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). Hum. Mol. Genet.6, 659–664 (1997). ArticleCASPubMed Google Scholar
Richard, I. et al. Mutations in the proteolytic enzyme Calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell81, 27–40 (1995). ArticleCASPubMed Google Scholar
Bolliger-Stucki, B., Lord, S. T. & Furlan, M. Fibrinogen Milano XII: a dysfunctional variant containing 2 amino acid substitutions, α-R16C and γ-G165R. Blood98, 351–357 (2001). ArticleCASPubMed Google Scholar
Goodyer, P. R., Clow, C., Reade, T. & Girardin, C. Prospective analysis and classification of patients with cystinuria identified in a newborn screening program. J. Pediatr.122, 568–572 (1993). ArticleCASPubMed Google Scholar
Kerst, B. et al. Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy. Neuromuscul. Disord.10, 572–577 (2000). ArticleCASPubMed Google Scholar
Redston, M. et al. The APCI1307K allele and breast cancer risk. Nature Genet.20, 13–14 (1998). ArticleCASPubMed Google Scholar
Scharf, J. M. et al. Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics. Nature Genet.20, 83–86 (1998). ArticleCASPubMed Google Scholar
Phelan, C. M. et al. Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus. Nature Genet.12, 309–311 (1996). ArticleCASPubMed Google Scholar
Cazeneuve, C. et al. Identification of MEFV-independent modifying genetic factors for familial Mediterranean fever. Am. J. Hum. Genet.67, 1136–1143 (2000). CASPubMedPubMed Central Google Scholar
Bykhovskaya, Y. et al. Candidate locus for a nuclear modifier gene for maternally inherited deafness. Am. J. Hum. Genet.66, 1905–1910 (2000). ArticleCASPubMedPubMed Central Google Scholar
Box, N. F. et al. MC1R genotype modifies risk of melanoma in families segregating CDKN2A mutations. Am. J. Hum. Genet.69, 765–773 (2001). ArticleCASPubMedPubMed Central Google Scholar
Sertie, A. L., Sousa, A. V., Steman, S., Pavanello, R. C. & Passos-Bueno, M. R. Linkage analysis in a large Brazilian family with van der Woude syndrome suggests the existence of a susceptibility locus for cleft palate at 17p11. −2-11.−1. Am. J. Hum. Genet.65, 433–440 (1999). ArticleCASPubMedPubMed Central Google Scholar
Gill, J. C., Endres-Brooks, J., Bauer, P. J., Marks, W. J. J. & Montgomery, R. R. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood69, 1691–1695 (1987). CASPubMed Google Scholar
Mohlke, K. L. et al. Mvwf, a dominant modifier of murine von Willebrand factor, results from altered lineage-specific expression of a glycosyltransferase. Cell96, 111–120 (1999). ArticleCASPubMed Google Scholar
Wyss-Coray, T. et al. TGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice. Nature Med.7, 612–618 (2001). ArticleCASPubMed Google Scholar
Takaku, K. et al. Suppression of intestinal polyposis in _Apc_Δ716 knockout mice by an additional mutation in the cytosolic phospholipase A2 gene. J. Biol. Chem.275, 34013–34016 (2000). ArticleCASPubMed Google Scholar
Oshima, M. et al. Suppression of intestinal polyposis in _Apc_Δ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell87, 803–809 (1996). ArticleCASPubMed Google Scholar
Vockley, J., Rinaldo, P., Bennett, M. J., Matern, D. & Vladutiu, G. D. Synergistic heterozygosity: disease resulting from multiple partial defects in one or more metabolic pathways. Mol. Genet. Metab.71, 10–18 (2000). ArticleCASPubMed Google Scholar