Genetics of ovarian failure-New Life India

929 views

Published on

Newlife India has done research on Genetics of ovarian failure. Maire Peter has done the research on the same. By virtue of the extenssive reasearch we are able to give best results on IVF treatments.

Published in: Health & Medicine, Technology
0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
929
On SlideShare
0
From Embeds
0
Number of Embeds
5
Actions
Shares
0
Downloads
88
Comments
0
Likes
3
Embeds 0
No embeds

No notes for slide

Genetics of ovarian failure-New Life India

  1. 1. PRESENTS Genetics of Ovarian Failure By: Maire Peters 1
  2. 2. Age at natural menopause • Menopause is the cessation of reproductive function of the human ovaries. • The median age at menopause – in Europe from 50.1 to 52.8 years, – in North America from 50.5 to 51.4 years, – in Latin America from 43.8 to 53 years, – in Asia from 42.1 to 49.5 years. 2
  3. 3. Premature menopause • Premature ovarian failure/primary ovarian insufficiency (POF/POI) is a cause of female infertility due to the loss of normal ovarian function in women before the age of 40 years. • POI affects approximately 1 in 10,000 women by age 20; 1 in 1,000 women by age 30; 1 in 100 women by age 40. • Early menopause (EM) is defined as menopause occurring at 40-45 years of age. EM occurs in 510% of women. 3
  4. 4. Mechanisms leading to POI 4 Persani L et al. J Mol Endocrinol 2010;45:257-279
  5. 5. Causes of POI ≈ 25% FOXL2 FSHR ≈ 10% POI ≈5% ≈ 20% ≈ 65% Figure adapted from Shelling 2010 5
  6. 6. X chromosome defects X chromosome defects Frequency of POI Frequency in POI Turner’s syndrome 100% 4-5% Normal FMR1 premutation 13-26% 15% (familial) 3% (sporadic) 7-54 CGG repeats Translocations, deletions 55-200 CGG repeats 80-100% Premutation BMP15 variants 0-10% Full mutation Unknown 1.5% more than 200 repeats 6
  7. 7. Autosomal defects Autosomal defects Frequency in POI Complex diseases: galactosemia (GALT), BPES (FOXL2), mitochondrial (POLG), ovarian leukodystrophy (EIF2B) Rare FSH/LH resistance (FSHR and LHR) <1% INHA variants unknown GDF9 variants ≈1% NOBOX, FIGLA unknown Each single gene is responsible for less than 1-6% of POI. 7
  8. 8. Genes involved in POI pathogenesis 8 Persani L et al. J Mol Endocrinol 2010;45:257-279
  9. 9. GWASs in POI Ethnicity Sample size (cases/controls) Replication Region SNP Reference Korean 24/24 98/218 - - Pyun et al., 2012 Chinese 391/895 400/800 8q22.3 8 SNPs Qin et al., 2012 European 99/235 60/90 - - Knauff et al., 2009 GWAS – Genome-wide association study 9
  10. 10. Genes associated with age at natural menopause Function Genes Related genes DNA repair EXO1, HELQ, UIMC1, TLK1, POLG, PRIM1 FAM175A, FANCI Immune function NLRP11, BAT2 IL11 X-chromosome inactivation ASH2L EIF4EBP1 Hormonal regulation - FSHB Known binding partner for FMR1 TDRD3 Various functions RHBDL2, FNDC4, MCM8, SYCP2L, TMEM150B EIF2B4 These 17 variants explain 2.5–4.1% of the population variation in menopausal age (Stolk et al., 2012). 10
  11. 11. Genetics of early menopause • EM has a substantial genetic component. • A woman whose mother had an EM has a 6-fold increased risk of having EM. • Large GWAS with sample size of 3,500 cases (women with menopause before 45 years of age) and 13,500 controls (Perry et al., 2013). • For all 17 variants associated with age at natural menopause, the allele that was associated with younger menopause age was also associated with increased risk of EM and POI (Perry et al., 2013). 11
  12. 12. Genetics of early menopause • Combining the effect of the 17 variants shows a larger effect on EM risk than smoking. • It is hypothesized that EM and POI represent the tail of the menopause distribution, with individuals carrying more age at menopauselowering variants having increased risk of EM and POI (Perry et al., 2013). 12
  13. 13. Future perspectives The discovery of additional genetic components involved in the determination of menopause age should make it possible to predict the onset of menopause, enabling women to make informed reproductive choices. 13
  14. 14. Thank you for your attention 14

×