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Variants in Deleted in AZoospermia-Like (DAZL) are correlated with reproductive parameters in men and women

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Abstract

Qualitative and quantitative defects in human germ cell production that result in infertility are common and determined at least in part by genetic factors [Matzuk and Lamb, Nat Cell Biol 4(Suppl):s41–s49, 2002]. Yet, very few genes that are associated with germ cell defects in humans have been identified. In this study, we examined whether variants of the Deleted in AZoospermia-Like (DAZL) gene are associated with measures of germ cell production in three distinct populations of men and women. We identified 95 sequence variants in DAZL and further analyzed twelve single nucleotide polymorphisms (SNPs) that were present across ethnicities. We found that seven of the twelve SNPs were associated with at least one of the parameters studied (age at premature ovarian failure or menopause, total sperm count, or total motile sperm count). Surprisingly, many alleles exhibited opposing effects in men and women, which may be a result of different genetic requirements in male and female germ cells. Single SNP and haplotype analysis suggested that SNPs in the DAZL gene may act jointly to affect common reproductive characteristics in the human population.

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Acknowledgments

We thank Anne Chang, Nicole Morison, and Vladimir Bakalov for technical assistance, Vanessa Angeles, Rhoda Chang, Anthony Dobson, Mark Fox, Joanna Gonsalves, Kehkooi Kee, Fred Moore, and Cory Nicholas for helpful comments and criticisms, and the UCSF GCF personnel for assistance with sequencing and analysis. This work was supported by fellowships from the National Science Foundation and Achievement Rewards for College Scientists to JYT, and by grants from the Sandler Family Foundation, the Searle Scholar Program and the National Institutes of Child Health and Human Development (R01 HD37095 and R01 HD047721-01A1) to RARP.

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology, and Reproductive Sciences, Department of Urology, Program in Human Embryonic Stem Cell Biology, Center for Reproductive Sciences, University of California at San Francisco, San Francisco, CA, 94143, USA

    Joyce Y. Tung, Mitchell P. Rosen, Paul J. Turek, Marcelle I. Cedars & Renee A. Reijo Pera

  2. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA

    Lawrence M. Nelson

  3. Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, 94143, USA

    John S. Witte

  4. OB/gyn Epidemiology Center, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Daniel W. Cramer

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  1. Joyce Y. Tung
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  2. Mitchell P. Rosen
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  3. Lawrence M. Nelson
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  4. Paul J. Turek
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  5. John S. Witte
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  6. Daniel W. Cramer
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  7. Marcelle I. Cedars
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  8. Renee A. Reijo Pera
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Correspondence to Renee A. Reijo Pera.

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Joyce Y. Tung and Mitchell P. Rosen have contributed equally

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Tung, J.Y., Rosen, M.P., Nelson, L.M. et al. Variants in Deleted in AZoospermia-Like (DAZL) are correlated with reproductive parameters in men and women. Hum Genet 118, 730–740 (2006). https://doi.org/10.1007/s00439-005-0098-5

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