Genomics can improve reproduction in several ways: 1) Tools like PCR, microarrays, and next generation sequencing can detect single gene disorders and polygenic disorders from genomes. 2) Non-invasive preimplantation testing from maternal blood and preimplantation genetic testing of embryos can screen for inherited disorders and aneuploidies before pregnancy. 3) In vitro fertilization with preimplantation genetic testing allows transferring only unaffected embryos and avoiding genetic diseases for conditions like cancers and blood disorders.

1. How Genomics can
Improve Reproduction
2018
Hesham Al-Inany, PhD
kaainih@yahoo.com

4. Short arm ( p )
………………………
Long arm ( q )

5. Genome
A genome is all the DNA in the cell,
including its genes in a very complex
sequence.
Many genes are co-expressed

7. Tools
PCR : detection of single gene disorder.
Micro-array (DNA chips) specially used
for polygenic disorders
NGS: most advanced

9. Interpretation of CGH array

11. ComparisonComparison courtesy of Dr. Tony Gordon, Genesis
Genetics

12. • NIPT(Non invasive prenatal testing)
•asinglematernal blood draw
••PGT(Preimplantation genetic Testing)
•~70%-80% of total testing
•PGD
•Screensfor inherited disorders
such asCystic Fibrosis
•20-30% of total testing

13.  NIPT measures circulating cell-free DNA (cffDNA)
from placenta present in maternal blood
 Comprises ~10% of DNA in maternal blood
 Increases with gestational age
 As early as 9 weeks gestation
(NIPT)

14. Fetal
cfDNA
(20%)
Maternal
cfDNA
Chromosomes: 1 2 3
……
21 Trisomy 21
VS
CountingNOT TO SCALE
10% more
Chr21
cfDNA in
T21

15. Increased maternal age
 Increased risk on Combination or triple
test
 Anxiety for invasive procedure (AC /
CVS)
Indications

16. PGTPGT
Avoidance of miscarriageAvoidance of miscarriage ??
Avoidance of aneuploidy at birthAvoidance of aneuploidy at birth YESYES
Improved live birth rate....Improved live birth rate.... NONO (?)(?)
Avoidance of genetic diseaseAvoidance of genetic disease YESYES

17. Miscarriagerateafter PGT do not increasewith
age
*SART, ** Harton et al. (2013) Fertil Steril
PGS **
No PGS *
Maternal age

19. Does PGT help increase pregnancy rate in
IVF?
21 April 20173rt GANNA Annual Meeting
19
Moniek Twisk et al., Hum
Reprod; 20013

20. So How to use it ?
Doctors successfully screened embryos for
gene mutation linked to early onset
Alzheimer's disease JAMA, 2002

21. IVF + PGT
Transfer only unaffected embryos
affected affectedaffected

22. Families with Cancer
Familial Adenomatous Polyposis
(FAP)
Multiple Endocrine Neoplasia 2
Breast cancer (BRCA1 and BRCA2
genes )
Hereditary non-polyposis colorectal
cancer
All these cancers are autosomal
dominant traits

23. Reality : Two IVF-PGS children without BRCA1 mutation

24. Other applications:
Thalassemia
Found most
frequently in the
Mediterranean

25. Haemophilia
(a) Bleeding around elbow. (b) A retinal bleed. (c) Repeated bleeds into joints
produce severe arthritis.

26. Using FISH for PGS of
X-linked disorders
Three colour FISH
X ( green)
Y (red)
Chromosome 18 to
control for normal
diploidy
Male
Female

28. 10 oocytes
8 fertilized
5 survive biopsy
6 cleave to 8-16 cell
1 no diagnosis
1 aneuploid
2 males
1 embryo for replacement
Practical realities
Attrition of embryos
Practical realities
Attrition of embryos
Example for a sex linked disorder
e.g. Haemophilia / Duchenne MD

29. IVF associated risks
- high cost
- risk of not getting pregnant
- increased risk of a multiple birth
- risk of OHSS (Difficult to balance
adequate egg numbers and the risk of
OHSS ).

30. Conclusion
It is just a step to the future