Bardet‐Biedl Syndrome, an Oligogenic Disease

Abstract

Bardet‐Biedl syndrome (BBS) is a rare multisystemic disorder characterized by defects in renal function, obesity, mental retardation, retinal degeneration and polydactyly. The disease is transmitted primarily in an autosomal recessive fashion but can also exhibit oligogenic inheritance. Twelve BBS genes have been identified to date. Based on localization and functional studies of their protein products, the underlying cause of the disease phenotype is defects in ciliary function which accounts for the pleiotropic nature of the disease. Though it is still unclear exactly how these genes function in cellular signalling pathways, evidence suggests that they are important in a number of fundamental pathways, including the Wnt signalling pathway.

Keywords: Bardet‐Biedl syndrome; cilium; basal body; oligogenic; Wnt

Figure 1.

Contribution of the 12 known BBS genes to Bardet‐Biedl syndrome. Representative graph of the percentage contribution of each known BBS gene to BBS cases. Families with three mutations in two BBS genes were assigned to the primary locus (the BBS locus with two mutant alleles). Modified from Katsanis, .

Figure 2.

Two pedigrees showing the autosomal recessive inheritance pattern of BBS. (a) Pedigree of a consanguineous family, in which the unaffected parents are both carriers of a nonsense mutation in BBS5. Three of the five children are homozygous for the mutant allele and, therefore, affected. Their heterozygous siblings are unaffected (adapted from Li et al., , reproduced by permission from Cell). (b) An autosomal recessive pedigree showing allelic heterogeneity. Two unaffected parents bear two different frameshift mutations in BBS10, respectively. The son bearing both mutant alleles in the same gene are affected (Stoetzel et al., ).

Figure 3.

Differences in penetrance. (a) Both siblings (asterisks) inherited two mutations in BBS2 from their unaffected parents. However, only one sibling is affected with the disease, challenging the autosomal recessive model. (b) The difference can be explained by the presence of a third mutant allele in BBS6. The sibling bearing a nonsense mutant allele of BBS6 is affected, whereas the sibling that is homozygous wildtype for BBS6 is unaffected, supporting a digenic and triallelic model of inheritance (adapted from Katsanis et al., , reproduced by permission from Science).

Figure 4.

Differences in expressivity. (a) In two siblings bearing the same BBS1 genotype, the phenotypes differ in severity. One sibling has only mild mental retardation, whereas the second suffers from severe mental retardation in addition to obesity, delayed speech development and other developmental abnormalities. (b) The difference can be explained by the presence of a third mutant allele in BBS6, consistent with a triallelic model. (c) Another family bearing BBS1 mutations had three affected siblings with the same BBS1 genotype. Two siblings developed early onset severe retinitis pigmentosa, whereas the third only developed a mild form of night blindness later in life. (d) Analysis of the BBS2 genotype explains the difference; the severely affected siblings both bear a third mutation in BBS2, whereas the more mildly affected sibling is wildtype (adapted from Badano et al., , reproduced by permission from Human Molecular Genetics; adapted from Katsanis, , reproduced by permission from Human Molecular Genetics).

Figure 5.

BBS4 in microtubule network organization. (a) BBS4 interacts with PCM1 and PCM1‐associated cargo to localize to the centriolar satellites. This function is most likely as a result of its interaction with the p150 subunit of dynactin. (b) If BBS4 function is absent or aberrant, PCM1 does not localize properly to the centriolar satellites, resulting in microtubule network disorganization. (c) A BBS4 dominant negative mutation results in binding of PCM1 and cargo, but inefficient loading of p150, resulting in mislocalization and microtubule disorganization defects (adapted from Kim et al., , reproduced by permission from Nature Genetics).

close

References

Andersen KL, Echwald SM, Larsen LH et al. (2005) Variation of the McKusick‐Kaufman gene and studies of relationships with common forms of obesity. The Journal of Clinical Endocrinology and Metabolism 90: 225–230.

Ansley SJ, Badano JL, Blacque OE et al. (2003) Basal body dysfunction is a likely cause of pleiotropic Bardet‐Biedl syndrome. Nature 425: 628–633.

Baala L, Romano S, Khaddour R et al. (2007) The Meckel‐Gruber syndrome gene, MKS3, is mutated in Joubert syndrome. American Journal of Human Genetics 80: 186–194.

Badano JL, Ansley SJ, Leitch CC et al. (2003a) Identification of a novel Bardet‐Biedl syndrome protein, BBS7, that shares structural features with BBS1 and BBS2. American Journal of Human Genetics 72: 650–658.

Badano JL, Kim JC, Hoskins BE et al. (2003b) Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet‐Biedl patients with two mutations at a second BBS locus. Human Molecular Genetics 12: 1651–1659.

Badano JL, Leitch CC, Ansley SJ et al. (2006a) Dissection of epistasis in oligogenic Bardet‐Biedl syndrome. Nature 439: 326–330.

Badano JL, Mitsuma N, Beales PL and Katsanis N (2006b) The ciliopathies: an emerging class of human genetic disorders. Annual Review of Genomics and Human Genetics 7: 125–148.

Badano JL, Teslovich TM and Katsanis N (2005) The centrosome in human genetic disease. Nature Reviews. Genetics 6: 194–205.

Beales PL, Badano JL, Ross AJ et al. (2003) Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non‐Mendelian Bardet‐Biedl syndrome. American Journal of Human Genetics 72: 1187–1199.

Beales PL, Elcioglu N, Woolf AS, Parker D and Flinter FA (1999) New criteria for improved diagnosis of Bardet‐Biedl syndrome: results of a population survey. Journal of Medical Genetics 36: 437–446.

Beales PL, Katsanis N, Lewis RA et al. (2001) 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. American Journal of Human Genetics 68: 606–616.

Beales PL, Parfrey PS and Katsanis N (2004) The Bardet‐Biedl and Alstrom syndromes. In: Maher E and Saggar‐Malik A (eds) Genetics of Renal Disease, pp. 361–398. London: Oxford University Press.

Beales PL, Warner AM, Hitman GA, Thakker R and Flinter FA (1997) Bardet‐Biedl syndrome: a molecular and phenotypic study of 18 families. Journal of Medical Genetics 34: 92–98.

Beisson J and Wright M (2003) Basal body/centriole assembly and continuity. Current Opinion in Cell Biology 15: 96–104.

Benzing T, Simons M and Walz G (2007) Wnt signaling in polycystic kidney disease. Journal of the American Society of Nephrology 18: 1389–1398.

Bergsma DR and Brown KS (1975) Assessment of ophthalmologic, endocrinologic and genetic findings in the Bardet‐Biedl syndrome. Birth Defects Original Article Series 11:132–136.

Blacque OE and Leroux MR (2006) Bardet‐Biedl syndrome: an emerging pathomechanism of intracellular transport. Cellular and Molecular Life Sciences 63: 2145–2161.

Blacque OE, Reardon MJ, Li C et al. (2004) Loss of C. elegans BBS‐7 and BBS‐8 protein function results in cilia defects and compromised intraflagellar transport. Genes and Development 18: 1630–1642.

Blatch GL and Lassle M (1999) The tetratricopeptide repeat: a structural motif mediating protein–protein interactions. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology 21: 932–939.

Bruford EA, Riise R, Teague PW et al. (1997) Linkage mapping in 29 Bardet‐Biedl syndrome families confirms loci in chromosomal regions 11q13, 15q22.3‐q23, and 16q21. Genomics 41: 93–99.

Carmi R, Rokhlina T, Kwitek‐Black AE et al. (1995) Use of a DNA pooling strategy to identify a human obesity syndrome locus on chromosome 15. Human Molecular Genetics 4: 9–13.

Chang B, Khanna H, Hawes N et al. (2006) In‐frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early onset retinal degeneration in the rd16 mouse. Human Molecular Genetics 15: 1847–1857.

Chiang AP, Beck JS, Yen HJ et al. (2006) Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet‐Biedl syndrome gene (BBS11). Proceedings of the National Academy of Sciences of the USA 103: 6287–6292.

Chiang AP, Nishimura D, Searby C et al. (2004) Comparative genomic analysis identifies an ADP‐ribosylation factor‐like gene as the cause of Bardet‐Biedl syndrome (BBS3). American Journal of Human Genetics 75: 475–484.

Cox GF, Hansen RM, Quinn N and Fulton AB (2003) Retinal function in carriers of Bardet‐Biedl syndrome. Archives of Ophthalmology 121: 804–810.

Croft JB, Morrell D, Chase CL and Swift M (1995) Obesity in heterozygous carriers of the gene for the Bardet‐Biedl syndrome. American Journal of Medical Genetics 55: 12–15.

Croft JB and Swift M (1990) Obesity, hypertension, and renal disease in relatives of Bardet‐Biedl syndrome sibs. American Journal of Medical Genetics 36: 37–42.

Dammermann A and Merdes A (2002) Assembly of centrosomal proteins and microtubule organization depends on PCM‐1. The Journal of Cell Biology 159: 255–266.

Dascher C and Balch WE (1994) Dominant inhibitory mutants of ARF1 block endoplasmic reticulum to golgi transport and trigger disassembly of the golgi apparatus. The Journal of Biological Chemistry 269: 1437–1448.

Davis EE, Brueckner M and Katsanis N (2006) The emerging complexity of the vertebrate cilium: new functional roles for an ancient organelle. Developmental Cell 11: 9–19.

de Pontual L, Pelet A, Clement‐Ziza M et al. (2007) Epistatic interactions with a common hypomorphic RET allele in syndromic Hirschsprung disease. Human Mutation 28:790–796.

den Hollander AI, Koenekoop RK, Yzer S et al. (2006) Mutations in the CEP290 (NPHP6) gene are a frequent cause of leber congenital amaurosis. American Journal of Human Genetics 79: 556–561.

Eichers ER, Abd‐El‐Barr MM, Paylor R et al. (2006) Phenotypic characterization of Bbs4 null mice reveals age‐dependent penetrance and variable expressivity. Human Genetics 120: 211–226.

Eichers ER, Lewis RA, Katsanis N and Lupski JR (2004) Triallelic inheritance: a bridge between Mendelian and multifactorial traits. Annals of Medicine 36: 262–272.

Fan Y, Esmail MA, Ansley SJ et al. (2004) Mutations in a member of the ras superfamily of small GTP‐binding proteins causes Bardet‐Biedl syndrome. Nature Genetics 36: 989–993.

Farag TI and Teebi AS (1988) Bardet‐Biedl and Laurence‐Moon syndromes in a mixed Arab population. Clinical Genetics 33: 78–82.

Farag TI and Teebi AS (1989) High incidence of Bardet‐Biedl syndrome among the Bedouin. Clinical Genetics 36: 463–464.

Fath MA, Mullins RF, Searby C et al. (2005) Mkks‐null mice have a phenotype resembling Bardet‐Biedl syndrome. Human Molecular Genetics 14: 1109–1118.

Forti E, Aksanov O and Birk RZ (2007) Temporal expression pattern of Bardet‐Biedl syndrome genes in adipogenesis. The International Journal of Biochemistry and Cell Biology 39: 1055–1062.

Gerdes JM and Katsanis N (2005) Microtubule transport defects in neurological and ciliary disease. Cellular and Molecular Life Sciences 62: 1556–1570.

Ghadami M, Tomita HA, Najafi MT et al. (2000) Bardet‐Biedl syndrome type 3 in an Iranian family: clinical study and confirmation of disease localization. American Journal of Medical Genetics 94: 433–437.

Gherman A, Davis EE and Katsanis N (2006) The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia. Nature Genetics 38: 961–962.

Gill SR, Schroer TA, Szilak I et al. (1991) Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein. The Journal of Cell Biology 115: 1639–1650.

Green JS, Parfrey PS, Harnett JD et al. (1989) The cardinal manifestations of Bardet‐Biedl syndrome, a form of Laurence‐Moon‐Biedl syndrome. The New England Journal of Medicine 321: 1002–1009.

Hichri H, Stoetzel C, Laurier V et al. (2005) Testing for triallelism: analysis of six BBS genes in a Bardet‐Biedl syndrome family cohort. European Journal of Human Genetics 13: 607–616.

Hou JW (2004) Bardet‐Biedl syndrome initially presenting as McKusick‐Kaufman syndrome. Journal of the Formosan Medical Association=Taiwan Yi Zhi 103: 629–632.

Iannaccone A, Mykytyn K, Persico AM et al. (2005) Clinical evidence of decreased olfaction in Bardet‐Biedl syndrome caused by a deletion in the BBS4 gene. American Journal of Medical Genetics. Part A 132: 343–346.

Karmous‐Benailly H, Martinovic J, Gubler MC et al. (2005) Antenatal presentation of Bardet‐Biedl syndrome may mimic meckel syndrome. American Journal of Human Genetics 76: 493–504.

Katsanis N (2004) The oligogenic properties of Bardet‐Biedl syndrome. Human Molecular Genetics 13(Spec No 1): R65–71.

Katsanis N, Ansley SJ, Badano JL et al. (2001) Triallelic inheritance in Bardet‐Biedl syndrome, a Mendelian recessive disorder. Science 293: 2256–2259.

Katsanis N, Beales PL, Woods MO et al. (2000) Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet‐Biedl syndrome. Nature Genetics 26: 67–70.

Katsanis N, Eichers ER, Ansley SJ et al. (2002) BBS4 is a minor contributor to Bardet‐Biedl syndrome and may also participate in triallelic inheritance. American Journal of Human Genetics 71: 22–29.

Katsanis N, Lewis RA, Stockton DW et al. (1999) Delineation of the critical interval of Bardet‐Biedl syndrome 1 (BBS1) to a small region of 11q13, through linkage and haplotype analysis of 91 pedigrees. American Journal of Human Genetics 65: 1672–1679.

Keller R (2002) Shaping the vertebrate body plan by polarized embryonic cell movements. Science 298: 1950–1954.

Kim JC, Badano JL, Sibold S et al. (2004) The Bardet‐Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression. Nature Genetics 36: 462–470.

Kim JC, Ou YY, Badano JL et al. (2005) MKKS/BBS6, a divergent chaperonin‐like protein linked to the obesity disorder Bardet‐Biedl syndrome, is a novel centrosomal component required for cytokinesis. Journal of Cell Science 118: 1007–1020.

Klein D (1971) Genetic approach to the nosology of retinal disorders. Birth Defects Original Article Series 7: 52–82.

Klein D and Ammann F (1969) The syndrome of Laurence‐Moon‐Bardet‐Biedl and allied diseases in Switzerland. Clinical, genetic and epidemiological studies. Journal of the Neurological Sciences 9: 479–513.

Kulaga HM, Leitch CC, Eichers ER et al. (2004) Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nature Genetics 36: 994–998.

Kwitek‐Black AE, Carmi R, Duyk GM et al. (1993) Linkage of Bardet‐Biedl syndrome to chromosome 16q and evidence for non‐allelic genetic heterogeneity. Nature Genetics 5: 392–396.

Kyttala M, Tallila J, Salonen R et al. (2006) MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in meckel syndrome. Nature Genetics 38: 155–157.

Laurier V, Stoetzel C, Muller J et al. (2006) Pitfalls of homozygosity mapping: an extended consanguineous Bardet‐Biedl syndrome family with two mutant genes (BBS2, BBS10), three mutations, but no triallelism. European Journal of Human Genetics 14: 1195–1203.

Leppert M, Baird L, Anderson KL et al. (1994) Bardet‐Biedl syndrome is linked to DNA markers on chromosome 11q and is genetically heterogeneous. Nature Genetics 7: 108–112.

Li JB, Gerdes JM, Haycraft CJ et al. (2004) Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell 117: 541–552.

Lowe SL, Wong SH and Hong W (1996) The mammalian ARF‐like protein 1 (Arl1) is associated with the golgi complex. Journal of Cell Science 109(Pt 1): 209–220.

Macklin MT (1936) The Laurence‐Moon Biedl syndrome: a genetic study. The Journal of Heredity 27.

Mykytyn K, Braun T, Carmi R et al. (2001) Identification of the gene that, when mutated, causes the human obesity syndrome BBS4. Nature Genetics 28: 188–191.

Mykytyn K, Mullins RF, Andrews M et al. (2004) Bardet‐Biedl syndrome type 4 (BBS4)‐null mice implicate Bbs4 in flagella formation but not global cilia assembly. Proceedings of the National Academy of Sciences of the USA 101: 8664–8669.

Mykytyn K, Nishimura DY, Searby CC et al. (2003) Evaluation of complex inheritance involving the most common Bardet‐Biedl syndrome locus (BBS1). American Journal of Human Genetics 72: 429–437.

Mykytyn K, Nishimura DY, Searby CC et al. (2002) Identification of the gene (BBS1) most commonly involved in Bardet‐Biedl syndrome, a complex human obesity syndrome. Nature Genetics 31: 435–438.

Nauli SM, Alenghat FJ, Luo Y et al. (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nature Genetics 33: 129–137.

Nishimura DY, Fath M, Mullins RF et al. (2004) Bbs2‐null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. Proceedings of the National Academy of Sciences of the USA 101: 16588–16593.

Nishimura DY, Searby CC, Carmi R et al. (2001) Positional cloning of a novel gene on chromosome 16q causing Bardet‐Biedl syndrome (BBS2). Human Molecular Genetics 10: 865–874.

Nishimura DY, Swiderski RE, Searby CC et al. (2005) Comparative genomics and gene expression analysis identifies BBS9, a new Bardet‐Biedl syndrome gene. American Journal of Human Genetics 77: 1021–1033.

Ou G, Blacque OE, Snow JJ, Leroux MR and Scholey JM (2005) Functional coordination of intraflagellar transport motors. Nature 436: 583–587.

Ou G, Koga M, Blacque OE et al. (2007) Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles. Molecular Biology of the Cell 18: 1554–1569.

Pan X, Ou G, Civelekoglu‐Scholey G et al. (2006) Mechanism of transport of IFT particles in C. elegans cilia by the concerted action of kinesin‐II and OSM‐3 motors. The Journal of Cell Biology 174: 1035–1045.

Park TJ, Haigo SL and Wallingford JB (2006) Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and hedgehog signaling. Nature Genetics 38: 303–311.

Polychonapos D, Tsipas D and Leanis D (1963) Laurence‐Moon‐Bardet‐Biedl syndrome. Acta Neurol Psychiat Hel 2.

Reymond A, Meroni G, Fantozzi A et al. (2001) The tripartite motif family identifies cell compartments. The EMBO Journal 20: 2140–2151.

Rosenbaum JL and Witman GB (2002) Intraflagellar transport. Nature Reviews. Molecular Cell Biology 3: 813–825.

Ross AJ, May‐Simera H, Eichers ER et al. (2005) Disruption of Bardet‐Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nature Genetics 37: 1135–1140.

Sayer JA, Otto EA, O'Toole JF et al. (2006) The centrosomal protein nephrocystin‐6 is mutated in joubert syndrome and activates transcription factor ATF4. Nature Genetics 38: 674–681.

Schachat AP and Maumenee IH (1982) Bardet‐Biedl syndrome and related disorders. Archives of Ophthalmology 100: 285–288.

Sheffield VC, Carmi R, Kwitek‐Black A et al. (1994) Identification of a Bardet‐Biedl syndrome locus on chromosome 3 and evaluation of an efficient approach to homozygosity mapping. Human Molecular Genetics 3: 1331–1335.

Slavotinek AM, Searby C, Al‐Gazali L et al. (2002) Mutation analysis of the MKKS gene in McKusick‐Kaufman syndrome and selected Bardet‐Biedl syndrome patients. Human Genetics 110: 561–567.

Slavotinek AM, Stone EM, Mykytyn K et al. (2000) Mutations in MKKS cause Bardet‐Biedl syndrome. Nature Genetics 26: 15–16.

Smaoui N, Chaabouni M, Sergeev YV et al. (2006) Screening of the eight BBS genes in Tunisian families: no evidence of triallelism. Investigative Ophthalmology & Visual Science 47: 3487–3495.

Smith UM, Consugar M, Tee LJ et al. (2006) The transmembrane protein meckelin (MKS3) is mutated in Meckel‐Gruber syndrome and the wpk rat. Nature Genetics 38: 191–196.

Stearns T, Willingham MC, Botstein D and Kahn RA (1990) ADP‐ribosylation factor is functionally and physically associated with the golgi complex. Proceedings of the National Academy of Sciences of the USA 87: 1238–1242.

Stern C (1960) Principles of Human Genetics, pp. 240–375. San Francisco, CA: W.H. Freeman and Co.

Stoetzel C, Laurier V, Davis EE et al. (2006) BBS10 encodes a vertebrate‐specific chaperonin‐like protein and is a major BBS locus. Nature Genetics 38: 521–524.

Stoetzel C, Muller J and Laurier V (2007) Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate‐specific branch of chaperonin‐related proteins in Bardet‐Biedl syndrome. American Journal of Human Genetics 80.

Takada T, Iida K, Sasaki H, Taira M and Kimura H (2005) Expression of ADP‐ribosylation factor (ARF)‐like protein 6 during mouse embryonic development. The International Journal of Developmental Biology 49: 891–894.

Tobin JL and Beales PL (2007) Bardet‐Biedl syndrome: beyond the cilium. Pediatric Nephrology (Berlin, Germany) 22:926–936.

Torayama I, Ishihara T and Katsura I (2007) Caenorhabditis elegans integrates the signals of butanone and food to enhance chemotaxis to butanone. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 27: 741–750.

Torban E, Kor C and Gros P (2004) Van Gogh‐like2 (strabismus) and its role in planar cell polarity and convergent extension in vertebrates. Trends in Genetics 20: 570–577.

White DR, Ganesh A, Nishimura D et al. (2007) Autozygosity mapping of Bardet‐Biedl syndrome to 12q21.2 and confirmation of FLJ23560 as BBS10. European Journal of Human Genetics 15: 173–178.

Yen HJ, Tayeh MK, Mullins RF et al. (2006) Bardet‐Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function. Human Molecular Genetics 15: 667–677.

Young TL, Penney L, Woods MO et al. (1999a) A fifth locus for Bardet‐Biedl syndrome maps to chromosome 2q31. American Journal of Human Genetics 64: 900–904.

Young TL, Woods MO, Parfrey PS et al. (1999b) A founder effect in the Newfoundland population reduces the Bardet‐Biedl syndrome I (BBS1) interval to 1 cM. American Journal of Human Genetics 65: 1680–1687.

Young TL, Woods MO, Parfrey PS et al. (1998) Canadian Bardet‐Biedl syndrome family reduces the critical region of BBS3 (3p) and presents with a variable phenotype. American Journal of Medical Genetics 78: 461–467.

Further Reading

Beales PL (2005) Lifting the lid on pandora's box: the Bardet‐Biedl syndrome. Current Opinion in Genetics & Development 15: 315–323.

Blacque OE and Leroux MR (2006) Bardet‐Biedl syndrome: an emerging pathomechanism of intracellular transport. Cellular and Molecular Life Sciences 63: 2145–2161.

Katsanis N, Lupski JR and Beales PL (2001) Exploring the molecular basis of Bardet‐Biedl syndrome. Human Molecular Genetics 10: 2293–2299.

Marshall WF (2007) What is the function of centrioles? Journal of Cellular Biochemistry 100: 916–922.

Oti M and Brunner HG (2007) The modular nature of genetic diseases. Clinical Genetics 71: 1–11.

Pan J, Wang Q and Snell WJ (2005) Cilium‐generated signaling and cilia‐related disorders. Laboratory Investigation: A Journal of Technical Methods and Pathology 85: 452–463.

Singla V and Reiter JF (2006) The primary cilium as the cell's antenna: signaling at a sensory organelle. Science (New York) 313: 629–633.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Liu, Yangfan, Zaghloul, Norann A, and Katsanis, Nicholas(Sep 2007) Bardet‐Biedl Syndrome, an Oligogenic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020227]