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In Silico Analysis of Functional SNPs in Genes of Complete Androgen Insensitivity Syndrome (CAIS): A Retrospective, Case–Control Study

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Abstract

Background

Complete androgen insensitivity syndrome (CAIS) is one of the categories of androgen insensitivity syndrome (AIS) described as complete failure of the cell to react to androgens with external genitalia of a normal female. People with AIS condition are genetically male, with XY karyotype in each cell, but their bodies are unable to respond to male sex hormones (called androgens). It is associated with infertility as well as develo** cancerous conditions. The genetic association of CAIS involves polymorphism of genes such as NR5A1, SOX9, SRD5A2, CBX2, GATA4, and SRY. Their mutation and participation in genetics of CAIS can be studied by Single Nucleotide polymorphism (SNP) analysis which is a way to detect genetic variations. SNP in coding region leads to synonymous and non-synonymous mutations. Hence, this study highlights analysis of SNPs associated with CAIS. Our aim is to study SNP analysis of NR5A1, SOX9, SRD5A2, CBX2, GATA4, SRY genes in Complete Androgen Insensitivity Syndrome.

Methods

SIFT and Polyphen analysis was performed for all the genes and samples were subjected for PCR-SSCP technique.

Results

SNPs were analyzed for the genes associated with CAIS. Benign and damaging SNPs were identified. DNA Samples were amplified using PCR technique and they will be analyzed using Single-strand conformation polymorphism (SSCP).

Conclusions

As SNPs have decreased stability, damaging and benign character, they can be used as candidate hallmarks in study of Complete Androgen Insensitivity Syndrome.

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References

  1. Dong Y, Yi Y, Hu H, Zhang R, et al. A novel mutation in the SRY gene of a Chinese 46, XY female patient with unilateral mixed germ cell tumor. J Reprod Contracept. 2016;27:82–8.

    Google Scholar 

  2. Hornig NC, Holterhus PM. Molecular basis of androgen insensitivity syndromes. Mol Cell Endocrinol. 2021;523: 111146.

    Article  CAS  PubMed  Google Scholar 

  3. Tadokoro R, Bunch T, Schwabe JW, Hughes IA, Murphy JC. Comparison of the molecular consequences of different mutations at residue 754 and 690 of the androgen receptor (AR) and androgen insensitivity syndrome (AIS) phenotype. Clin Endocrinol. 2009;71:253–60.

    Article  CAS  Google Scholar 

  4. Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA. Androgen insensitivity syndrome. Best Pract Res Clin Endocrinol Metab. 2015;29:569–80.

    Article  CAS  PubMed  Google Scholar 

  5. Infante JB, Alvelos MI, Bastos M, Carrilho F. Lemos MC Complete androgen insensitivity syndrome caused by a novel splice donor site mutation and activation of a cryptic splice donor site in the androgen receptor gene. J Steroid Biochem Mol Biol. 2016;155:63–6.

    Article  CAS  PubMed  Google Scholar 

  6. Hughes IA, Werner R, Bunch T, Hiort O. Androgen insensitivity syndrome. Semin Reprod Med. 2012;30(05):432–42.

    Article  CAS  PubMed  Google Scholar 

  7. Wu JY, McGown IN, Lin L, Achermann JC, et al. A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46, XY patients with disorders of sex development. Clin Endocrinol. 2013;78:545–50.

    Article  CAS  Google Scholar 

  8. Fabbri HC, de Andrade JG, Soardi FC, de Calais FL, et al. Cys65Tyr mutation in NR5A1 gene in three 46, XY siblings with normal testosterone levels and their mother with primary ovarian insufficiency. BMC Med Genet. 2014;15:1.

    Article  Google Scholar 

  9. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4:1073–81.

    Article  CAS  PubMed  Google Scholar 

  10. Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013;76(1):7–20.

    Google Scholar 

  11. Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res. 2001;11:863–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ng PC, Henikoff S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31:3812–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ng PC, Henikoff S. Predicting the effects of amino acid substitutions on protein function. Annu Rev Genomics Hum Genet. 2006;7:61–80.

    Article  CAS  PubMed  Google Scholar 

  14. Rajasekaran R, Sudandiradoss C, Doss CG, Sethumadhavan R. Identification and in silico analysis of functional SNPs of the BRCA1 gene. Genomics. 2007;90:447–52.

    Article  CAS  PubMed  Google Scholar 

  15. Jääskeläinen J. Molecular biology of androgen insensitivity. Mol Cell Endocrinol. 2012;352:4–12.

    Article  PubMed  Google Scholar 

  16. Wang S, Xu H, An W, Zhu D, Li D. Mutational analysis of the androgen receptor gene in two Chinese families with complete androgen insensitivity syndrome. Exp Ther Med. 2016;11:2277–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Suntharalingham JP, Buonocore F, Duncan AJ, Achermann JC. DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best Pract Res Clin Endocrinol Metab. 2015;29:607–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nowacka-Woszuk J, Nizanski W, Klimowicz M, Switonski M. Normal male chromosome complement and a lack of the SRY and SOX9 gene mutations in a male pseudohermaphrodite dog. Anim Reprod Sci. 2007;98:371–6.

    Article  CAS  PubMed  Google Scholar 

  19. Beale JM, Creighton SM. Long-term health issues related to disorders or differences in sex development/intersex. Maturitas. 2016;94:143–8.

    Article  PubMed  Google Scholar 

  20. Hines M, Ahmed SF, Hughes IA. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome. Arch Sex Behav. 2003;32:93–101.

    Article  PubMed  Google Scholar 

  21. Lanciotti L, Cofini M, Leonardi A, Bertozzi M, et al. Different clinical presentations and management in complete androgen insensitivity syndrome (CAIS). Int J Environ Res Public Health. 2019;16(7):1268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank the management of Vellore Institute of technology for providing excellent facilities to carry out this study.

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Authors and Affiliations

  1. Assistant professor at Symbiosis Institute of Health Sciences (SIHS), Symbiosis International (Deemed University), Mulshi, Lavale, Maharashtra, 412115, India

    Shalaka S. Ramgir

  2. Quality Assurance-Executive, GLR Laboratories Pvt. Ltd., Chennai, Tamilnadu, 600068, India

    Sivakumar Annamalai

  3. Associate Professor, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamilnadu, 632014, India

    V. G. Abilash

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  1. Shalaka S. Ramgir
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Correspondence to Shalaka S. Ramgir.

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All processes executed in research regarding human individuals had been approved by the Institutional ethical community, Vellore Institute of Technology, Vellore, India.

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Informed consent was obtained from all the individual participants included in this study.

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Shalaka Sudhir Ramgir is an Assistant professor; Sivakumar Annamalai is an Quality Assurance-Executive; Abilash V.G. is an associate professor.

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Ramgir, S.S., Annamalai, S. & Abilash, V.G. In Silico Analysis of Functional SNPs in Genes of Complete Androgen Insensitivity Syndrome (CAIS): A Retrospective, Case–Control Study. J Obstet Gynecol India 74, 136–143 (2024). https://doi.org/10.1007/s13224-023-01876-3

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