Skip to main content
SpringerLink
Log in

Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification

  • genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To develop a reliable preimplantation genetic diagnosis protocol for couples who both carry a mutant PKHD1 gene wishing to conceive children unaffected with autosomal recessive polycystic kidney disease (ARPKD).

Methods

Development of a unique protocol for preimplantation genetic testing using whole genome amplification of single blastomeres by multiple displacement amplification (MDA), and haplotype analysis with novel short tandem repeat (STR) markers from the PKHD1 gene and flanking sequences, and a case report of successful utilization of the protocol followed by successful IVF resulting in the birth of an infant unaffected with ARPKD.

Results

We have developed 20 polymorphic STR markers suitable for linkage analysis of ARPKD. These linked STR markers have enabled unambiguous identification of the PKHD1 haplotypes of embryos produced by at-risk couples.

Conclusions

We have developed a reliable protocol for preimplantation genetic diagnosis of ARPKD using single-cell MDA products for PKHD1 haplotyping.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Harris PC, Torres VE. Polycystic kidney disease. Annu Rev Med. 2009;60:321–37.

    Article  CAS  PubMed  Google Scholar 

  2. Dell KM, Sweeney WE, Avner ED. Polycystic kidney disease. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, editors. Pediatric nephrology. 6th ed. Heidelberg: Springer-Verlag; 2009. p. 849–88.

    Google Scholar 

  3. Sweeney WE, Avner ED. Molecular and cellular pathophysiology of Autosomal recessive polycystic kidney disease. Cell Tissue Res. 2006;326:671–85.

    Article  CAS  PubMed  Google Scholar 

  4. Dell KM, Avner ED (July 2008) Autosomal recessive polycystic kidney disease. In: GeneClinics: Online Clinical Genetic Information Resource; www.geneclinics.org

  5. Sweeney WE, Avner ED. Renal cystic disease: new insights for the clinician. Pediatr Clin North Am. 2006;53:889–909.

    Article  PubMed  Google Scholar 

  6. European Polycystic Kidney Disease Consortium. The polycystic kidney disease 1 gene encodes a 14kb transcript and lies within a duplicated region on chromosome 16. Cell. 1994;77:881–94.

    Article  Google Scholar 

  7. Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, et al. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science. 1996;272:1339–42.

    Article  CAS  PubMed  Google Scholar 

  8. Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, et al. The polycystic kidney disease (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet. 1995;10:151–60.

    Article  CAS  PubMed  Google Scholar 

  9. Ward CJ, Hogan MC, Rossetti S, Walker D, Sneddon T, Wang X, et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet. 2002;30:259–69.

    Article  PubMed  Google Scholar 

  10. Onuchic LF, Furu L, Nagasawa Y, Hou X, Eggermann T, Ren Z, et al. PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel ß-helix 1 repeats. Am J Hum Genet. 2002;70:1305–17.

    Article  CAS  PubMed  Google Scholar 

  11. Bick DP, Lau EC. Preimplantation genetic diagnosis. Pediatr Clin North Am. 2006;53(4):559–77.

    Article  PubMed  Google Scholar 

  12. Swanson A, Strawn E, Lau E, Bick D. Preimplantation genetic diagnosis: technology and clinical applications. WMJ. 2007;106(3):145–51.

    PubMed  Google Scholar 

  13. Spits C, Sermon K. PGD for monogenic disorders: aspects of molecular biology. Prenat Diagn. 2008;29(1):50–6.

    Article  Google Scholar 

  14. Fallon L, Harton GL, Sisson ME, Rodriguez E, Field LK, Fugger EF, et al. Preimplantation genetic diagnosis for spinal muscular atrophy type I. Neurology. 1999;53(5):1087–90.

    CAS  PubMed  Google Scholar 

  15. Xu K, Shi ZM, Veeck LL, Hughes MR, Rosenwaks Z. First unaffected pregnancy using preimplantation genetic diagnosis for sickle cell anemia. JAMA. 1999;281:1701–6.

    Article  CAS  PubMed  Google Scholar 

  16. Consugar MB, Anderson SA, Rossetti S, Pankratz S, Ward CJ, Torra R, et al. Haplotype analysis improves molecular diagnostics of autosomal recessive polycystic kidney disease. Am J Kidney Dis. 2005;45(1):77–87.

    Article  CAS  PubMed  Google Scholar 

  17. Bick SL, Bick BP, Wells BE, Roesler MR, Strawn EY, Lau EC. Preimplantation HLA haplotyping using tri-, tetra-, and pentanucleotide short tandem repeats for HLA matching. J Assist Reprod Genet. 2008;25:323–31.

    Article  PubMed  Google Scholar 

  18. Verlinsky Y, Rechitsky S, Verlinsky O, Chistokhina A, Sharapova T, Masciangelo C, et al. Preimplantation diagnosis for neurofibromatosis. Reprod Biomed Online. 2002;4(3):218–22.

    Article  PubMed  Google Scholar 

  19. Michaelides K, Tuddenham EGD, Turner C, Lavender B, Lavery SA. Live birth following the first mutation specific pre-implantation genetic diagnosis for haemophilia A. Thromb Haemost. 2006;95:373–9.

    CAS  PubMed  Google Scholar 

  20. Sanchez-Garcia JF, Fallardo D, Ramirez L, Vidal F. Multiple fluorescent analysis of four short tandem repeats for rapid haemophilia A molecular diagnosis. Thromb Haemost. 2005;94(5):1099–103.

    CAS  PubMed  Google Scholar 

  21. Spits C, De Rycke M, Verpoest W, Lissens W, Van Steirteghem A, Liebaers I, et al. Preimplantation genetic diagnosis for Marfan syndrome. Fertil Steril. 2006;86(2):310–20.

    Article  PubMed  Google Scholar 

  22. Christofidou C, Sofocleous C, Vrettou C, Destouni A, Traeger-Synodinos J, Kekou K, et al. PGD for X-linked and gender-dependent disorders using a robust, flexible single-tube PCR protocol. Reprod Biomed Online. 2009;19(3):418–25.

    Article  CAS  PubMed  Google Scholar 

  23. Spits C, De Rycke M, Van Ranst N, Joris H, Verpoest W, Lissens W, et al. Preimplantation genetic diagnosis for neurofibromatosis type 1. Mol Hum Reprod. 2005;11(5):381–7.

    Article  CAS  PubMed  Google Scholar 

  24. Malcov M, Ben-Yosef D, Schwartz T, Mey-Raz N, Azem F, Lessing JB, et al. Preimplantation genetic diagnosis (PGD) for Duchenne muscular dystrophy (DMD) by triplex-nested PCR. Prenat Diagn. 2005;25:1200–5.

    Article  CAS  PubMed  Google Scholar 

  25. Gigarel N, Frydman N, Burlet P, Kerbrat V, Tachdjian G, Fanchin R, et al. Preimplantation genetic diagnosis for autosomal recessive polycystic kidney disease. Reprod Biomed Online. 2008;16(1):152–8.

    Article  CAS  PubMed  Google Scholar 

  26. Handyside AH, Robinson MD, Simpson RJ, Omar MB, Shaw M-A, Grudzinskas JG, et al. Isothermal whole genome amplification from single and small numbers of cells: a new era for preimplantation genetic diagnosis of inherited disease. Mol Hum Reprod. 2004;10(10):676–72.

    Article  Google Scholar 

  27. Hellani A, Coskun S, Benkhalifa M, Thakhi A, Sakati N, Al-Odaib A, et al. Multiple displacement amplification on single cell and possible PGD applications. Mol Hum Reprod. 2004;10(11):847–52.

    Article  CAS  PubMed  Google Scholar 

  28. Spits C, Le Caignec C, De Rycke M, Van Haute L, Van Steirteghem A, Liebaers I, et al. Optimization and evaluation of single-cell whole-genome multiple displacement amplification. Hum Mutat. 2006;27(5):496–503.

    Article  CAS  PubMed  Google Scholar 

  29. Spits C, Le Caignec C, De Rycke M, Van Haute L, Van Steirteghem A, Liebaers I, et al. Whole-genome multiple displacement amplification from single cells. Nat Protoc. 2006;1(4):1965–70.

    Article  CAS  PubMed  Google Scholar 

  30. Renwick PJ, Lewis CM, Abbs S, Ogilvie CM. Determination of the genetic status of cleavage-stage human embryos by microsatellite marker analysis following multiple displacement amplification. Prenat Diagn. 2007;27:206–15.

    Article  CAS  PubMed  Google Scholar 

  31. Ren Z, Zhou C, Xu Y, Deng J, Zeng H, Zeng Y. Mutation and haplotype analysis for Duchenne muscular dystrophy by single cell multiple displacement amplification. Mol Hum Reprod. 2007;13(6):431–6.

    Article  CAS  PubMed  Google Scholar 

  32. Ren Z, Zeng H-T, Xu Y-W, Zhuang G-L, Deng J, Zhang C, et al. Preimplantation genetic diagnosis for Duchenne muscular dystrophy by multiple displacement amplification. Fertil Steril. 2009;91(2):359–64.

    Article  CAS  PubMed  Google Scholar 

  33. Glentis S, SenGupta S, Thornhill A, Wang R, Craft I, Harper JC. Molecular comparison of single cell MDA products derived from different cell types. Reprod BioMed Online. 2009;19:89–98.

    Article  CAS  PubMed  Google Scholar 

  34. Qubbaj W, Al-Aqeel AI, Al-Hassnan Z, Al-Duraihim A, Awartani K, Al-Rejjal R, et al. Preimplantation genetic diagnosis of Morquio disease. Prenat Diagn. 2008;28(10):900–3.

    Article  CAS  PubMed  Google Scholar 

  35. Burlet P, Frydman N, Gigarel N, Kerbrat V, Tachdjian G, Feyereisen E, et al. Multiple displacement amplification improves PGD for fragile X syndrome. Mol Hum Reprod. 2006;12(10):647–52.

    Article  CAS  PubMed  Google Scholar 

  36. Obradors A, Fernández E, Rius M, Oliver-Bonet M, Martínez-Fresno M, Benet J et al (2009) Outcome of twin babies free of Von Hippel-Lindau disease after a double-factor preimplantation genetic diagnosis: monogenetic mutation analysis and comprehensive aneuploidy screening. Fertil Steril 91(3):933.e1–7. [Epub 2009 Jan 10]

    Google Scholar 

  37. Dean FB, Hosono S, Fang L, Wu X, Faruqi AF, Bray-Ward P, et al. Comprehensive human genome amplification using multiple displacement amplification. Proc Natl Acad Sci USA. 2002;99:5261–6.

    Article  CAS  PubMed  Google Scholar 

  38. Hellani A, Sammour A, Johansson L, El-Sheikh A. Delivery of a normal baby after preimplantation genetic diagnosis for non-ketotic hyperglycinaemia. Reprod BioMed Online. 2008;16(6):893–7.

    Article  CAS  PubMed  Google Scholar 

  39. Lledo B, Ten J, Rodriguez-Arnedo D, Llacer J, Bernabeu R. Preimplantation genetic diagnosis of X-linked retinoschisis. Reprod BioMed Online. 2008;16(6):886–92.

    Article  PubMed  Google Scholar 

  40. Hellani A, Abu-Amero K, Azouri J, Al-Sharif H, Barblet H, El-Akoum S. Pregnancy after preimplantation genetic diagnosis for brachydactyly type B. Reprod Biomed Online. 2009;18(1):127–31.

    Article  PubMed  Google Scholar 

  41. Benson G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 1999;27(2):573–80.

    Article  CAS  PubMed  Google Scholar 

  42. Brownstein MJ, Carpten JD, Smith JR. Modulation of non-templated nucleotide addition by Taq DNA polymerase: primer modifications that facilitate genotyping. BioTechniques. 1996;20:1004–10.

    CAS  PubMed  Google Scholar 

  43. Altarescu G, Geva TE, Brooks B, Margalioth E, Levy-Lahad E, Renbaum P. PGD on a recombinant allele: crossover between the TSC2 gene and ‘linked’ markers impairs accurate diagnosis. Prenat Diagn. 2008;28(10):929–33.

    Article  CAS  PubMed  Google Scholar 

  44. Li Y, Kim H-J, Zheng C, Chow WHA, Lim J, Keenan B, et al. Primase-based whole genome amplification. Nucleic Acids Res. 2008;36(13):e79. Epub 2008 Jun 17.

    Article  PubMed  Google Scholar 

  45. Hellani A, Abu-Amero K, Azouri J, El-Akoum S. Successful pregnancies after application of array-comparative genomic hybridization in PGS-aneuploidy screening. Reprod BioMed Online. 2008;17(6):841–7.

    Article  CAS  PubMed  Google Scholar 

  46. Handyside AH, Harton GL, Mariani B, Thornhill AR, Affara N, Shaw M-A et al (2009 Oct. 25) Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes. J Med Genet. [Epub ahead of print]

  47. Kumar G, Garnova E, Reagin M, Vidali A. Improved multiple displacement amplification with phi29 DNA polymerase for genotyping of single human cells. BioTechniques. 2008;44(7):879–90.

    Article  CAS  PubMed  Google Scholar 

  48. Chow JF, Yeung WS, Lau EY, Lam ST, Tong T, Ng EH, Ho PC (2009) Singleton birth after preimplantation genetic diagnosis for Huntington disease using whole genome amplification. Fertil Steril 92(2):828.e7–10. [Epub 2009 Jun 9].

    Google Scholar 

Download references

Acknowledgments

The excellent support of our colleagues Barbara Szlendakova, Amy Granlund, Dr. Peter vanTuinen, Brent Wells, Sarah Bick and Bridget Lawler are gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Eduardo C. Lau, Marleen M. Janson, Ellis D. Avner & David P. Bick

  2. Children’s Research Institute, Children’s Hospital and Health System of Wisconsin, TBRC Room C2450, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Eduardo C. Lau, Marleen M. Janson, Ellis D. Avner & David P. Bick

  3. Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Eduardo C. Lau, Marleen M. Janson & David P. Bick

  4. Reproductive Medicine Clinic, Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, Milwaukee, WI, 53226, USA

    Mark R. Roesler & Estil Y. Strawn

  5. Comprehensive Renal Disease Program, Children’s Hospital of Wisconsin, Milwaukee, WI, 53226, USA

    Ellis D. Avner

  6. Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Estil Y. Strawn & David P. Bick

Authors
  1. Eduardo C. Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marleen M. Janson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark R. Roesler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ellis D. Avner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Estil Y. Strawn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David P. Bick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eduardo C. Lau.

Additional information

Capsule Preimplantation Genetic Diagnosis of Autosomal Recessive Polycystic Kidney Disease using Multiple Displacement Amplification and Haplotype Analysis of PKHD1 Gene with Linked Short Tandem Repeat Markers

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lau, E.C., Janson, M.M., Roesler, M.R. et al. Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification. J Assist Reprod Genet 27, 397–407 (2010). https://doi.org/10.1007/s10815-010-9432-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-010-9432-5

Keywords

Search

Navigation