GENOME-WIDE ASSOCIATION STUDIES OF PREMATURE OVARIAN FAILURE (LITERATURE REVIEW)

Sribna V. O., Voznesenskaya T. Yu., Blashkiv T. V.

LITERATURE REVIEWS

Scentific article

Genome-wide association study (GWAS) is a field of biomedical research related to the study of associations between genomic variants and phenotypic traits. GWAS is to identify genetic risk factors in order to make a reasonable prediction of susceptibility to the disease, as well as to identify the biological basis of susceptibility to the disease to develop new strategies for prevention and treatment. It is known that 1,0-3,7% of the female population suffers from premature ovarian failure (POF) under the age of 40 and 0.1% under 30. Due to the fact that the etiology of most cases of POF is unclear, and a few decades ago few specific genetic causes of POF were known, the aim of this study was to collect data on full-genomic studies of associations of premature ovarian failure. Based on the analysis of the literature, the following generalizations can be made: GWAS is a modern powerful tool in identifying the causes of diseases, including POF, which require a personalized medical approach. Studies of this type usually compare the genomes of a group of sick people with different phenotypes with the genomes of the control group, which includes similar in age, sex and other characteristics of healthy people. With the help of GWAS it is possible to compare not only the genomes of patients, but also healthy people with different manifestations of the same phenotypic trait. The material for the study are DNA samples of the genome of each participant in the study, in which using microchips look for single nucleotide polymorphisms. If it is possible to identify variants of genomes (more precisely, a set of alleles), which are probably more common in people with this disease, it is said that this variant is associated (or associated) with the disease. Unlike methods that test one or more specific regions of the genome, GWAS uses the complete DNA sequence of the patient. It should be noted that this approach to research does not detect mutations that cause the disease, but only a greater or lesser significant correlation with the disease or other symptom. Today, due to the limited, as a rule, sample size, it is difficult to identify probable genetic candidates for POF. However, this type of research is developing rapidly in the world, its cost will decrease, and the possibility of using such research in medical practice in the near future for individual and accurate approach to the diagnosis of POF should be considered. Currently, the GWAS of the genome of patients with POF in Ukraine is relevant for the detection of known mutations in genes associated with this disease. Given the growing number of women worldwide with premature ovarian failure, the involvement of genomic DNA (GWAS) research from individuals representing major regions of Ukraine will provide data for medical research in a large, little-studied population

genome-wide association studies, premature ovarian failure, decreased ovarian reserve, ovarian aging, correction of ovarian aging, genetic factors of ovarian aging

1. Rossetti R, Ferrari I, Bonomi M, Persani L. Genetics of primary ovarian insufficiency. Clinical Genetics. 2017;91:183-198. DOI: 10.1111/ cge.12921.
2. Wittenberger M, Hagerman R, Sherman S, McConkie-Rosell A, Welt C, Rebar R, et al. The FMR1 premutation and reproduction. Fertil Steril. 2007;3:456-465. DOI: doi.org/10.1016/j.fertnstert.2006.09.004.
3. Visscher P, Brown M, McCarthy M, Yang J. Five years of GWAS discovery. Am J Hum Genet. 2012;90(1):7-24. DOI: 10.1016/j. ajhg.2011.11.029.
4. Abecasis G, Auton A, Brooks L, DePristo M, Durbin R. 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;1(491):56-65. DOI: doi.org/10.1038/nature11632.
5. Burke W, Khoury M, Stewart A, Zimmern R, Bellagio Group. The path from genome-based research to population health: development of an international public health genomics network. Genet Med. 2006;8(7):451-458. DOI: doi.org/10.1097/01.gim.0000228213.72256.8c.
6. Bush W, Moore J. Chapter 11: Genome-wide association studies. PLoS Comput Biol. 2012;8(12):e1002822. DOI: 10.1371/journal. pcbi.1002822.
7. Oleksyk O, Shchubelka K, Wolfsberger W. Genome wide search for associations in patients with acromegaly in the Ukrainian population. Endocrinology. 2019;24(2):146-152. DOI: doi.org/10.31793/1680-1466.2019. 24-2.146.
8. Oleksyk T, Wolfsberger W, Weber A, Shchubelka K, Oleksyk O, Levchuk O, et al. Genome diversity in Ukraine. GigaScience. 2021;10(1):1- 14. DOI: doi.org/10.1093/gigascience/giaa159.
9. Qin Y, Jiao X, Simpson J, Chen Z. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update. 2015;21:787-808. DOI: 10.1093/humupd/dmv036.
10. Kang H, Lee S, Kim M, Song J, Bae S, Kim N, et al. Parathyroid hormone-responsive B1 gene is associated with premature ovarian failure. Hum Reprod. 2008;6:1457-1465. DOI: 10.1093/humrep/den086.
11. Knauff E, Blauw H, Pearson P, Kok K, Wijmenga C, Veldink J, et al. Copy number variants on the X chromosome in women with primary ovarian insufficiency. Fertil Steril. 2011;5:1584-1588. DOI: 10.1016/j.fertnstert.2011. 01.018.
12. Pyun J, Cha D, Kwack K. LAMC1 gene is associated with premature ovarian failure. Maturitas. 2012;4:402-406. DOI: 10.1016/j. maturitas.2012.01.011.
13. Zhao S, Li G, Dalgleish R, Vujovic S, Jiao X, Li J. Transcription factor SOHLH1 potentially associated with primary ovarian insufficiency. Fertil. Steril. 2015;103:548-553. DOI: 10.1016/j.fertnstert.2014.11.011.
14. Heddar A, Dessen P, Flatters D, Misrahi M. Novel STAG3 mutations in a Caucasian family with primary ovarian insufficiency. Mol. Genet. Genomics. 2019;294:1527-1534. DOI: 10.1007/s00438-019-01594-4.
15. de Vries L, Behar D, Smirin-Yosef P, Lagovsky I, Tzur S, Basel-Vanagaite L. Exome sequencing reveals SYCE1 mutation associated with autosomal recessive primary ovarian insufficiency. J Clin Endocrinol Metab. 2014;99:2129-2132. DOI: 10.1210/jc.2014-1268.
16. Smirin-Yosef P, Zuckerman-Levin N, Tzur S, Granot Y, Cohen L, Sachsenweger J, et al. A biallelic mutation in the homologous recombination repair gene SPIDR is associated with human gonadal dysgenesis. J Clin Endocrinol Metab. 2017;102:681-688. DOI: 10.1210/jc.2016- 2714.
17. Zangen D, Kaufman Y, Zeligson S, Perlberg S, Fridman H, Kanaan M. XX ovarian dysgenesis is caused by a PSMC3IP/HOP2 mutation that abolishes coactivation of estrogen-driven transcription. Am J Hum Genet. 2011;89:572-579. DOI: 10.1016/j.ajhg.2011.09.006.
18. Zhe J, Chen S, Chen X, Liu Y, Li Y, Zhou X. A novel heterozygous splice-altering mutation in HFM1 may be a cause of premature ovarian insufficiency. J Ovarian Res. 2019;12:61. DOI: 10.1186/s13048-019-0537-x.
19. Carlosama C, Elzaiat M, Patino L, Mateus H, Veitia R, Laissue P. A homozygous donor splice-site mutation in the meiotic gene MSH4 causes primary ovarian insufficiency. Hum Mol Genet. 2017;26:3161-3166. DOI: 10.1093/hmg/ddx199.
20. Cannavo E, Sanchez A, Anand R, Ranjha L, Hugener J, Adam C, et al. Regulation of the MLH1-MLH3 endonuclease in meiosis Nature. 2020;586(7830):618-622. DOI: 10.1038/s41586-020-2592-2.
21. Wood-Trageser M, Gurbuz F, Yatsenko S, Jeffries E, Kotan L, Surti U. MCM9 mutations are associated with ovarian failure, short stature, and chromosomal instability. Am J Hum Genet. 2014;95:754-762. DOI: 10.1016/j.ajhg.2014.11. 002.
22. Desai S, Wood-Trageser M, Matic J, Chipkin J, Jiang H, Bachelot A. MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency. J Clin Endocrinol Metab. 2017;102:576-582. DOI: 10.1210/jc.2016-2565.
23. Qin Y, Guo T, Li G, Tang T, Zhao S, Jiao X. CSB-PGBD3 mutations cause premature ovarian failure. PLoS Genet. 2015;11:e1005419. DOI: 10.1371/ journal.pgen.1005419.
24. Weinberg-Shukron A, Renbaum P, Kalifa R, Zeligson S, Ben-Neriah Z, Dreifuss A. A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis. J Clin Invest. 2015;125:4295-4304. DOI: 10.1172/JCI83553.
25. Zhao M, Feng F, Chu C, Yue W, Li L. A novel EIF4ENIF1 mutation associated with a diminished ovarian reserve and premature ovarian insufficiency identified by whole-exome sequencing. J. Ovarian Res. 2019;12:119. DOI: 10.1186/s13048-019-0595-0.
26. Jiao X, Ke H, Qin Y, Chen Z-J. Molecular genetics of premature ovarian insufficiency. Trends Endocrinol. Metabol. 2018;29:795-807. DOI: 10.1016/j. tem.2018.07.002.
27. Jaillard S, Bell K, Akloul L, Walton K, McElreavy K, Stocker W. New insights into the genetic basis of premature ovarian insufficiency: Novel causative variants and candidate genes revealed by genomic sequencing. Мaturitas. 2020;141:9-19. DOI: 10.1016/j.maturitas.2020.06.004.

«Bulletin of problems biology and medicine» Issue 1 (163), 2022 year, 71-74 pages, index UDK 616-021: 616.092

10.29254/2077-4214-2022-1-163-71-74