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Microarray Analysis of a Large Number of Single-Nucleotide Polymorphisms in Individual Human Spermatozoa

  • Chapter
The Genetics of Male Infertility

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Abstract

Genetic studies in humans have been limited by various factors, including small family size and diploidy of the human genome. The ability to use individual spermatozoa as subjects has significantly facilitated these studies. However, because each sperm usually contains only one copy of the genome and the sensitivity of the available detection methods was low, single sperm could not be used for large-scale genetic analysis. After a series of enhancements, a high-throughput genotyping system has been developed. With this system, more than 1000 genetic markers consisting of single-nucleotide polymorphisms (SNPs) in a single sperm genome can be amplified to a detectable amount in a single tube. Sequences amplified from different polymorphic loci are then resolved by hybridizing these sequences to the corresponding probes spotted on a microarray. The allelic sequences of each SNP are then discriminated by the commonly used allele-specific single-base-extension assay with dideoxyribonucleotides labeled with different fluorescent dyes. Using single sperm cells as subjects, the highly sensitive and high-throughput multiplex genotyping system was used to analyze the physical structure of the human immunoglobulin heavy chain variable region that contains highly repetitive sequences and may not be easily analyzed with conventional methods. This system was also used to understand the contribution of meiotic recombination to haplotype structure formation in the human genome. The system may have various applications including study of genetic factors underlying male infertility.

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Authors and Affiliations

  1. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Honghua Li PhD

  2. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Xiangfeng Cui BS

  3. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Danielle M. Greenawalt PhD

  4. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Guohong Hu PhD

  5. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Nyam-Osor Chimge PhD

  6. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Sreemanta Pramanik PhD

  7. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Minjie Luo PhD

  8. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Hui-Yun Wang MD, PhD

  9. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Irina V. Tereshchenko MD, PhD

  10. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Marco A. Azaro PhD

  11. Department of Biometrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Yong Lin PhD

  12. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Qifeng Yang MD, PhD

  13. Department of Computer Science, University of Maryland, Baltimore County, Baltimore, MD

    James Y. Li BS

  14. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Yi Chu MS

  15. Department of Cellular and Molecular Physiology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA

    Zhenwu Lin PhD

  16. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Richeng Gao MS

  17. Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Li Shen MS

  18. Department of Molecular Biology, Princeton University, Princeton, NJ

    Christina J. DeCoste PhD

  19. Department of Biometrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ

    Weichung J. Shih PhD

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  1. Honghua Li PhD
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  17. Li Shen MS
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  18. Christina J. DeCoste PhD
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Editor information

Editors and Affiliations

  1. Departments of Surgery (Urology), Obstetrics and Gynecology, and Physiology, University of Utah School of Medicine, Salt Lake City, UT

    Douglas T. Carrell PhD

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Li, H. et al. (2007). Microarray Analysis of a Large Number of Single-Nucleotide Polymorphisms in Individual Human Spermatozoa. In: Carrell, D.T. (eds) The Genetics of Male Infertility. Humana Press. https://doi.org/10.1007/978-1-59745-176-5_4

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