Slide 1

Three Parent BabiesPrepared ByRicha Khatiwada

1

Three-parent baby a child in which the vast majority of DNA(nuclear) comes from the mother and father and a small amount of DNA (mitochondrial) comes from a female donor.

First three parent baby was born in Mexico in 2016 as a way of dodging inherited genetic disease.

Second three parent baby was born in Ukraine in 2017, designed to remedy infertility.INTRODUCTION2

MITOCHONDRIA Generate energy Passed from mother to child Contains 37 genes Mutation can lead to fatal inherited diseases No cure or effective treatment

3

MITOCHONDRIAL DISEASES Caused bymutations, acquired or inherited, in mitochondrial DNA (mtDNA) or in nuclear genes that code for mitochondrial components.

As mtDNA is copied when mitochondria proliferate, they can accumulate random mutations, a phenomenon calledheteroplasmy.

Mitochondrial DNA mutations occur frequently, due to the lack of the error checking capability that mtDNA has.

4

FATAL ONESLeber's hereditary optic neuropathy(LHON) Degeneration ofretinalganglion cells(RGCs) and theiraxons Acute or subacute loss of central vision

Leigh syndrome Psychomotor regression Results in death within two to three years

Pearson syndromeAnemia Pancreas issues Lead to diabetes5

CYTOPLASMIC TRANSFER

Originally developed in the 1980s Mixture of mitochondrial genetic material From 1996 to 2001, Cohen performed the procedure 37 times, producing 17 babies for 13 couples. Boost" the eggs of older women who wanted to conceive but were having problemsThree children born through the technique were found to have developmental disorders (2 cases ofTurner's syndromeand one case ofpervasive developmental disorder.

6

PRONUCLEAR TRANSFER7

Contd Pronuclear transfer is the first mitochondrial replacement technique (MRT) developed in mouse embryos in 1983.

In Ukraine (2017) this technique was used in the birth of a baby boy.

Baby's mother had been through four unsuccessful rounds of conventional IVF.

She had embryonic arrest.

Embryo from pronuclear arrest avoided the condition.

8

SPINDLE TRANSFER

9

Contd First three parent baby boy was born in Mexico in 2016 using spindle transfer techniqe.

The boys mother carries genes forLeigh syndrome.

Around a quarter of hermitochondria have the disease-causing mutation. While she is healthy, Leigh syndrome was responsible for the deaths of her first two children.

Spindle transfer was done to create five embryos, only one of which developed normally. This embryo was implanted in the motherand the childwas born nine months later.10

POLAR BODY TRANSFERPolar bodyis a small cell with very little cytoplasm that is created when an egg cell divides.

The polar body can be used either in spindle transfer or pronuclear transfer.

It was first published in 2014.

It is considered promising as there is a greatly reduced chance for transmitting mitochondria from the recipient because polar bodies contain very few mitochondria, and it does not involve extracting material from the recipient's egg.11

12

MICE TRIALS

13

14Contd One study in mice found that when donated mitochondrial DNA wasnt a close match for the mothers original mitochondrial DNA, it led to accelerated aging of cells, metabolic disorders and obesity.

Since mitochondrial DNA doesnt change much with each generation, any complications from a genetic mismatch would eventually be passed on to the child's future children too.

FACTS The average number of births per year among women at risk for transmitting mtDNA disease is estimated to approximately 150 in theUnited Kingdomand 800 in theUnited States.

Prior to the development of MRT, and in places where it is not legal or feasible, the reproductive options for women who are at risk for transmitting mtDNA disease and who want to prevent transmission were using an egg from another woman, adoption, or childlessness.

In 2015 MRT was made legal in the United Kingdom.15

MRT involvespreimplantation genetic screeningof the mother,preimplantation genetic diagnosisafter the egg is fertilized, andin vitro fertilization. It has all the risks of those procedures.

A bit of cytoplasm (including mitochondria) is usually transferred along with the pronuclei.

As nuclear DNA codes for mitochondrial proteins, there is a theoritical risk of adverse "mito-nuclear" interactions.

There is a risk ofepigeneticmodification to DNA in the nucleus and mitochondria.

RISKS16

17

ETHICAL ISSUES Opponents argue that scientists are "playing God" and that children with three genetic parents may suffer both psychological and physical damage.

Using human embryos for in vitro research is controversial, as embryos are created specifically for research and the financial compensation of egg donors.

Implications for identity is another ethical concern with psychological and emotional impacts on a child's life regarding of a person's sense of identity.

It is also seen as destroying embryos.18

19REFERENCESBodkin, H. (12:09). Three-parent baby born to infertile couple in world first. The Telegraph. Retrieved from http://www.telegraph.co.uk/science/2017/01/18/three-parent-baby-born-infertile-couple-world-first/

Dockrill, P. (n.d.). World-First in Ukraine as three-Parent Baby Born to an Infertile Couple. Retrieved March 1, 2017, from http://www.sciencealert.com/world-first-in-ukraine-as-three-parent-baby-born-to-an-infertile-couple

Exclusive: Worlds first baby born with new 3 parent technique. (n.d.). Retrieved March 1, 2017, from https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/

Hamilton, G. (2015). The hidden risks for three-person babies. Nature News, 525(7570), 444. https://doi.org/10.1038/525444a

20Lebers hereditary optic neuropathy. (2017, February 18). In Wikipedia. Retrieved from https://en.wikipedia.org/w/index.php?title=Leber%27s_hereditary_optic_neuropathy&oldid=766084280

Mitochondrial disease. (2017, January 21). In Wikipedia. Retrieved from https://en.wikipedia.org/w/index.php?title=Mitochondrial_disease&oldid=761200224

Mitochondrial replacement therapy. (2017, February 28). In Wikipedia. Retrieved from https://en.wikipedia.org/w/index.php?title=Mitochondrial_replacement_therapy&oldid=767841023

Reference, G. H. (n.d.). Leigh syndrome. Retrieved March 2, 2017, from https://ghr.nlm.nih.gov/condition/leigh-syndrome

Saey, T. H. (2017, February 21). Three-parent babies explained. Retrieved March 1, 2017, from https://www.sciencenews.org/article/three-parent-babies-explained?mode=topic&context=49Contd

21

THANK YOU