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Genetic testing in renal disease

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Abstract

A revolution is happening in genetics! The decoding of the first genome in 2003 was a large international collaborative effort that took about 13 years at a cost of around $2.7 billion. Now, only a few years later, new technology allows the sequencing of an entire genome within a few weeks—and at a cost of less than $10,000. The vaunted $1000 genome is within reach. These extraordinary advances will undoubtedly transform the way we practice medicine. But, like any new technology, it carries risks, as well as benefits. As physicians, we need to understand the implications in order to best utilise these advances for our patients and to provide informed advice. In this review, our aim is to explain these new technologies, to separate the hype from the reality and to address some of the resulting questions and implications. The practical objective is to provide a simple overview of the available technologies and of purpose to which they are best suited.

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References

  1. Wright CF, Hall A, Zimmern RL (2010) Regulating direct-to-consumer genetic tests: what is all the fuss about? Genet Med. doi:10.1097/GIM.0b013e3181f69dd2

    Google Scholar 

  2. Kleta R, Bernardini I, Ueda M, Varade WS, Phornphutkul C, Krasnewich D, Gahl WA (2004) Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr 145:555–560

    Article  PubMed  Google Scholar 

  3. Kleta R, Kaskel F, Dohil R, Goodyer P, Guay-Woodford LM, Harms E, Ingelfinger JR, Koch VH, Langman CB, Leonard MB, Mannon RB, Sarwal M, Schneider JA, Skovby F, Sonies BC, Thoene JG, Trauner DA, Gahl WA (2005) First NIH/office of rare diseases conference on cystinosis: past, present, and future. Pediatr Nephrol 20:452–454

    Article  PubMed  Google Scholar 

  4. Bockenhauer D (2008) Diabetes insipidus. In: Geary DF, Schaefer F (eds) Comprehensive pediatric nephrology. Mosby Elsevier, Philadelphia, pp 489–498

    Chapter  Google Scholar 

  5. Hoekstra JA, van Lieburg AF, Monnens LA, Hulstijn-Dirkmaat GM, Knoers VV (1996) Cognitive and psychosocial functioning of patients with congenital nephrogenic diabetes insipidus. Am J Med Genet 61:81–88

    Article  PubMed  CAS  Google Scholar 

  6. Grantham JJ (2008) Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med 359:1477–1485

    Article  PubMed  CAS  Google Scholar 

  7. Mekahli D, Woolf AS, Bockenhauer D (2010) Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms. Pediatr Nephrol 25:2275–2282

    Article  PubMed  Google Scholar 

  8. Horikawa Y, Iwasaki N, Hara M, Furuta H, Hinokio Y, Cockburn BN, Lindner T, Yamagata K, Ogata M, Tomonaga O, Kuroki H, Kasahara T, Iwamoto Y, Bell GI (1997) Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 17:384–385

    Article  PubMed  CAS  Google Scholar 

  9. Bingham C, Bulman MP, Ellard S, Allen LI, Lipkin GW, Hoff WG, Woolf AS, Rizzoni G, Novelli G, Nicholls AJ, Hattersley AT (2001) Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease. Am J Hum Genet 68:219–224

    Article  PubMed  CAS  Google Scholar 

  10. Adalat S, Woolf AS, Johnstone KA, Wirsing A, Harries LW, Long DA, Hennekam RC, Ledermann SE, Rees L, van't Hoff W, Marks SD, Trompeter RS, Tullus K, Winyard PJ, Cansick J, Mushtaq I, Dhillon HK, Bingham C, Edghill EL, Shroff R, Stanescu H, Ryffel GU, Ellard S, Bockenhauer D (2009) HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 20:1123–1131

    Article  PubMed  CAS  Google Scholar 

  11. Bingham C, Ellard S, van't Hoff WG, Simmonds HA, Marinaki AM, Badman MK, Winocour PH, Stride A, Lockwood CR, Nicholls AJ, Owen KR, Spyer G, Pearson ER, Hattersley AT (2003) Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation. Kidney Int 63:1645–1651

    Article  PubMed  CAS  Google Scholar 

  12. Lindner TH, Njolstad PR, Horikawa Y, Bostad L, Bell GI, Sovik O (1999) A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta. Hum Mol Genet 8:2001–2008

    Article  PubMed  CAS  Google Scholar 

  13. Adalat S, Bockenhauer D, Ledermann SE, Hennekam RC, Woolf AS (2010) Renal malformations associated with mutations of developmental genes: messages from the clinic. Pediatr Nephrol 25:2247–2255

    Article  PubMed  Google Scholar 

  14. Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F (2004) Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 15:722–732

    Article  PubMed  Google Scholar 

  15. Buscher AK, Kranz B, Buscher R, Hildebrandt F, Dworniczak B, Pennekamp P, Kuwertz-Broking E, Wingen AM, John U, Kemper M, Monnens L, Hoyer PF, Weber S, Konrad M (2010) Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 5:2075–2084

    Article  PubMed  Google Scholar 

  16. Bockenhauer D, Carpentier E, Rochdi D, van't Hoff W, Breton B, Bernier V, Bouvier M, Bichet DG (2009) Vasopressin type 2 receptor V88M mutation: molecular basis of partial and complete nephrogenic diabetes insipidus. Nephron Physiol 114:p1–p10

    Article  PubMed  Google Scholar 

  17. Sadeghi H, Robertson GL, Bichet DG, Innamorati G, Birnbaumer M (1997) Biochemical basis of partial nephrogenic diabetes insipidus phenotypes. Mol Endocrinol 11:1806–1813

    Article  PubMed  CAS  Google Scholar 

  18. Bross P, Corydon TJ, Andresen BS, Jorgensen MM, Bolund L, Gregersen N (1999) Protein misfolding and degradation in genetic diseases. Hum Mutat 14:186–198

    Article  PubMed  CAS  Google Scholar 

  19. Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ (2004) Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304:600–602

    Article  PubMed  CAS  Google Scholar 

  20. Muller D, Kausalya PJ, Bockenhauer D, Thumfart J, Meij IC, Dillon MJ, van't Hoff W, Hunziker W (2006) Unusual clinical presentation and possible rescue of a novel claudin-16 mutation. J Clin Endocrinol Metab 91:3076–3079

    Article  PubMed  Google Scholar 

  21. Bernier V, Morello JP, Zarruk A, Debrand N, Salahpour A, Lonergan M, Arthus MF, Laperriere A, Brouard R, Bouvier M, Bichet DG (2006) Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 17:232–243

    Article  PubMed  CAS  Google Scholar 

  22. Bockenhauer D, Cruwys M, Kleta R, Halperin LF, Wildgoose P, Souma T, Nukiwa N, Cheema-Dhadli S, Chong CK, Kamel KS, Davids MR, Halperin ML (2008) Antenatal Bartter's syndrome: why is this not a lethal condition? Q J Med 101:927–942

    Article  CAS  Google Scholar 

  23. Bockenhauer D, van't Hoff W, Dattani M, Lehnhardt A, Subtirelu M, Hildebrandt F, Bichet DG (2010) Secondary nephrogenic diabetes insipidus as a complication of inherited renal diseases. Nephron Physiol 116:p23–p29

    Article  PubMed  CAS  Google Scholar 

  24. Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Tryggvason K, Scambler P (2002) 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

    Article  PubMed  CAS  Google Scholar 

  25. Weber S, Gribouval O, Esquivel EL, Moriniere V, Tete MJ, Legendre C, Niaudet P, Antignac C (2004) NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence. Kidney Int 66:571–579

    Article  PubMed  CAS  Google Scholar 

  26. Katsanis N, Ansley SJ, Badano JL, Eichers ER, Lewis RA, Hoskins BE, Scambler PJ, Davidson WS, Beales PL, Lupski JR (2001) Triallelic inheritance in Bardet–Biedl syndrome, a Mendelian recessive disorder. Science 293:2256–2259

    Article  PubMed  CAS  Google Scholar 

  27. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R (2008) SLCO1B1 variants and statin-induced myopathy—a genome-wide study. N Engl J Med 359:789–799

    Article  PubMed  CAS  Google Scholar 

  28. Bitner-Glindzicz M, Pembrey M, Duncan A, Heron J, Ring SM, Hall A, Rahman S (2009) Prevalence of mitochondrial 1555A– > G mutation in European children. N Engl J Med 360:640–642

    Article  PubMed  Google Scholar 

  29. Rovin BH, McKinley AM, Birmingham DJ (2009) Can we personalize treatment for kidney diseases? Clin J Am Soc Nephrol 4:1670–1676

    Article  PubMed  Google Scholar 

  30. Takada K, Arefayene M, Desta Z, Yarboro CH, Boumpas DT, Balow JE, Flockhart DA, Illei GG (2004) Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis. Arthritis Rheum 50:2202–2210

    Article  PubMed  CAS  Google Scholar 

  31. Gipson DS, Trachtman H, Kaskel FJ, Radeva MK, Gassman J, Greene TH, Moxey-Mims MM, Hogg RJ, Watkins SL, Fine RN, Middleton JP, Vehaskari VM, Hogan SL, Vento S, Flynn PA, Powell LM, McMahan JL, Siegel N, Friedman AL (2011) Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life. Kidney Int 79(6):678–85

    Google Scholar 

  32. Howie AJ (2010) Problems with 'focal segmental glomerulosclerosis'. Pediatr Nephrol. doi:10.1007/s00467-010-1701-0

    PubMed  Google Scholar 

  33. Thor A (2001) HER2–a discussion of testing approaches in the USA. Ann Oncol 12[Suppl 1]:S101–S107

    Article  PubMed  Google Scholar 

  34. Saif MW, Shah M (2009) K-ras mutations in colorectal cancer: a practice changing discovery. Clin Adv Hematol Oncol 7(45–53):64

    Google Scholar 

  35. van Krieken JH, Jung A, Kirchner T, Carneiro F, Seruca R, Bosman FT, Quirke P, Flejou JF, Plato Hansen T, de Hertogh G, Jares P, Langner C, Hoefler G, Ligtenberg M, Tiniakos D, Tejpar S, Bevilacqua G, Ensari A (2008) KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch 453:417–431

    Article  PubMed  Google Scholar 

  36. Hunt JL (2008) Molecular testing in solid tumors: an overview. Arch Pathol Lab Med 132:164–167

    PubMed  CAS  Google Scholar 

  37. Plesec TP, Hunt JL (2009) KRAS mutation testing in colorectal cancer. Adv Anat Pathol 16:196–203

    Article  PubMed  CAS  Google Scholar 

  38. Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA (2010) Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med 362:1181–1191

    Article  PubMed  CAS  Google Scholar 

  39. Edghill EL, Oram RA, Owens M, Stals KL, Harries LW, Hattersley AT, Ellard S, Bingham C (2008) Hepatocyte nuclear factor-1beta gene deletions—a common cause of renal disease. Nephrol Dial Transplant 23:627–635

    Article  PubMed  CAS  Google Scholar 

  40. Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C (2007) Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet 81:1057–1069

    Article  PubMed  CAS  Google Scholar 

  41. Moreno-De-Luca D, Mulle JG, Kaminsky EB, Sanders SJ, Myers SM, Adam MP, Pakula AT, Eisenhauer NJ, Uhas K, Weik L, Guy L, Care ME, Morel CF, Boni C, Salbert BA, Chandrareddy A, Demmer LA, Chow EW, Surti U, Aradhya S, Pickering DL, Golden DM, Sanger WG, Aston E, Brothman AR, Gliem TJ, Thorland EC, Ackley T, Iyer R, Huang S, Barber JC, Crolla JA, Warren ST, Martin CL, Ledbetter DH (2010) Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet 87:618–630

    Article  PubMed  CAS  Google Scholar 

  42. Shinawi M, Cheung SW (2008) The array CGH and its clinical applications. Drug Discov Today 13:760–770

    Article  PubMed  CAS  Google Scholar 

  43. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30:e57

    Article  PubMed  Google Scholar 

  44. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467

    Article  PubMed  CAS  Google Scholar 

  45. Schuster SC (2008) Next-generation sequencing transforms today's biology. Nat Methods 5:16–18

    Article  PubMed  CAS  Google Scholar 

  46. Kleta R, Romeo E, Ristic Z, Ohura T, Stuart C, Arcos-Burgos M, Dave MH, Wagner CA, Camargo SR, Inoue S, Matsuura N, Helip-Wooley A, Bockenhauer D, Warth R, Bernardini I, Visser G, Eggermann T, Lee P, Chairoungdua A, Jutabha P, Babu E, Nilwarangkoon S, Anzai N, Kanai Y, Verrey F, Gahl WA, Koizumi A (2004) Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder. Nat Genet 36:999–1002

    Article  PubMed  CAS  Google Scholar 

  47. Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M, Tobin J, Lieberer E, Sterner C, Landoure G, Arora R, Sirimanna T, Thompson D, Cross JH, van't Hoff W, Al Masri O, Tullus K, Yeung S, Anikster Y, Klootwijk E, Hubank M, Dillon MJ, Heitzmann D, Arcos-Burgos M, Knepper MA, Dobbie A, Gahl WA, Warth R, Sheridan E, Kleta R (2009) Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 360:1960–1970

    Article  PubMed  CAS  Google Scholar 

  48. Landoure G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi Y, Taye AA, Kong L, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Caterina MJ, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ (2009) Mutations in TRPV4 cause Charcot–Marie–Tooth disease type 2 C. Nat Genet 42:170–174

    Article  PubMed  Google Scholar 

  49. St Hilaire C, Ziegler SG, Markello T, Brusco A, Groden C, Gill F, Carlson-Donohoe H, Lederman RJ, Chen MY, Yang D, Siegenthaler MP, Arduino C, Mancini C, Freudenthal B, Stanescu H, Zdebik AA, Chaganti RK, Nussbaum R, Kleta R, Gahl WA, Boehm M (2011) N5TE mutations and arterial calcifications. N Engl J Med 364:432–442

    Article  PubMed  CAS  Google Scholar 

  50. The Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678

    Google Scholar 

  51. Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, Voinescu C, Patel N, Pearce K, Hubank M, Stephens HA, Laundy V, Padmanabhan S, Zawadzka A, Hofstra JM, Coenen MJ, den Heijer M, Kiemeney LA, Bacq-Daian D, Stengel B, Powis SH, Brenchley P, Feehally J, Rees AJ, Debiec H, Wetzels JF, Ronco P, Mathieson PW, Kleta R (2011) Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med 364:616–626

    Article  PubMed  CAS  Google Scholar 

  52. Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW, Oleksyk T, McKenzie LM, Kajiyama H, Ahuja TS, Berns JS, Briggs W, Cho ME, Dart RA, Kimmel PL, Korbet SM, Michel DM, Mokrzycki MH, Schelling JR, Simon E, Trachtman H, Vlahov D, Winkler CA (2008) MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 40:1175–1184

    Article  PubMed  CAS  Google Scholar 

  53. Kao WH, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, Li M, Coresh J, Patterson N, Tandon A, Powe NR, Fink NE, Sadler JH, Weir MR, Abboud HE, Adler SG, Divers J, Iyengar SK, Freedman BI, Kimmel PL, Knowler WC, Kohn OF, Kramp K, Leehey DJ, Nicholas SB, Pahl MV, Schelling JR, Sedor JR, Thornley-Brown D, Winkler CA, Smith MW, Parekh RS (2008) MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 40:1185–1192

    Article  PubMed  CAS  Google Scholar 

  54. Seri M, Cusano R, Gangarossa S, Caridi G, Bordo D, Lo Nigro C, Ghiggeri GM, Ravazzolo R, Savino M, Del Vecchio M, d'Apolito M, Iolascon A, Zelante LL, Savoia A, Balduini CL, Noris P, Magrini U, Belletti S, Heath KE, Babcock M, Glucksman MJ, Aliprandis E, Bizzaro N, Desnick RJ, Martignetti JA (2000) Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet 26:103–105

    Article  PubMed  CAS  Google Scholar 

  55. Kelley MJ, Jawien W, Ortel TL, Korczak JF (2000) Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. Nat Genet 26:106–108

    Article  PubMed  CAS  Google Scholar 

  56. Freedman BI, Kopp JB, Langefeld CD, Genovese G, Friedman DJ, Nelson GW, Winkler CA, Bowden DW, Pollak MR (2010) The apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African Americans. J Am Soc Nephrol 21:1422–1426

    Article  PubMed  CAS  Google Scholar 

  57. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329:841–845

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Child Health, University College London, London, UK

    Detlef Bockenhauer & Robert Kleta

  2. Centre for Nephrology, University College London, London, UK

    Detlef Bockenhauer, Alan J. Medlar & Robert Kleta

  3. North East Thames Regional Genetics Service Laboratories, Great Ormond Street Hospital for Children NHS Trust, London, UK

    Emma Ashton & Nick Lench

  4. Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK

    Detlef Bockenhauer

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  1. Detlef Bockenhauer
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  2. Alan J. Medlar
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  3. Emma Ashton
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  4. Robert Kleta
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Correspondence to Detlef Bockenhauer.

Glossary

Allele

refers to forms of DNA sequence. A SNP typically has two alleles: A vs. T or C vs. G. A gene can have many alleles, defined by several sequence variations within the sequence of the gene. In early genetics, allele referred to a variant of a gene that resulted in a certain phenotype, such as eye colour or blood group.

Amplicon

a stretch of DNA defined by the location of the two olgonucleotide primers used in the PCR. The stretch of DNA flanked by the primers will be amplified by PCR.

Compound heterozygous

refers to a situation in a recessive diseases, where the mutation found on one allele is different from that found on the other allele.

Exome

refers to the stretches of DNA in the genome that are actually protein-coding. It makes up only about 1% of the entire genome, but harbours approximately 85% of all disease-causing mutations. Whole-exome sequencing is becoming increasingly common for the identification of mutations in rare single-gene disorders, but is likely to be replaced by whole genome sequencing in the future.

Genotype

the genetic makeup of an individual. This can refer to a single nucleotide variation (e.g. A vs. T or C vs. G) or the combination of many such variations, for instance as determined by a SNP array.

Homozygous

if the two alleles in an individual are identical by descent. This can be for a single nucleotide (e.g. a SNP) or larger stretches of DNA (e.g. a gene).

Heterozygous

if the two alleles in an individual are different.

Linkage

describes the tendency of two loci to be inherited (linked) together when assessed across generations of a family. Loci in close physical proximity tend to be inherited together. Two loci are considered linked if they are co-inherited more often than by chance alone.

Linkage disequilibrium

describes the tendency of alleles to be inherited together when assessed across the population. It describes the difference between the observed allelic frequencies and what we would expect given truly random inheritance. The more commonly two alleles are inherited together, the stronger they are in linkage disequilibrium. In contrast to linkage, which reflects physical proximity only, linkage disequilibrium can also reflect other factors. For instance, two genes on separate chromosomes can be in linkage disequilibrium if they are functionally interdependent and evolved under the same constraints.

Locus

a physical location on a chromosome of a gene or DNA sequence.

Missense mutation

a mutation that results in a change of the encoded amino acid; for example, from lysine to threonine.

Nonsense mutation

a mutation that results in a premature stop codon.

Re-sequencing

refers to the multiple sequencing of individual DNA fragments common in next-generation sequencing. In contrast to conventional (Sanger) DNA sequencing, where each stretch of DNA is sequenced only once.

Risk allele

the allele of a SNP that is associated with a given disease. Genome-wide association studies investigate which form of a SNP (e.g. A or T) is associated with the disease. The associated form is called the risk allele.

SNP

single ucleotide polymorphism. Variation of a single nucleotide in the genome. SNPs are typically considered non-pathogenic and by definition have a frequency of >1% in the general population.

SNP array

a microarray or chip to determine the genotype of many SNP simultaneously. SNP arrays vary in size and may contain between 10,000 to >1,000,000 SNPs.

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Bockenhauer, D., Medlar, A.J., Ashton, E. et al. Genetic testing in renal disease. Pediatr Nephrol 27, 873–883 (2012). https://doi.org/10.1007/s00467-011-1865-2

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