Spina bifida and genetics by Margo Whiteford

Spina Bifida and Genetics Margo Whiteford Vice President IF

What Is A Gene?

DNA

What Is A Gene? ‘A recipe for the production of proteins used in the formation and the function of the body as it goes throughout life’

Chromosomes

Genetic Code

A C

T G

G

Sponge Cake Ingredients

4ozs Margarine 4ozs Caster sugar 6ozs Flour 2eggs

Method

Mix all the ingredients together and bake in an oven at 200C for 45 mins

Sponge Cake Ingredients

4ozs Margarine 4ozs Caster sugar 2ozs Flour 2eggs

Method

Mix all the ingredients together and bake in an oven at 200C for 45 mins

Perfect Baby Ingredients

ATT GCC TAC CTC GGG CTA ATC CTG AAT CGT CAT AGT CCG TAT

Method

CTG AAT CAG GGT CCG CTA GAG GGC TAC TTT AGC

Perfect Baby Ingredients 1 head 1 body 2 arms 2 legs

Method

Take a mother and father and mix together with a lot of love

Spelling mistake in recipe? or something else?

Family History

Family History

Family History

Family History

Family History

Multifactorial

Genetic Factors

Nongenetic Factors

What Are The Genetic Factors?

Genetic Factors

Perfect Baby Ingredients

ATT GCC TAC CTC GGG CTA ATC CTG AAT CGT CAT AGT CCG TAT

Method

CTG AAT CAG GGT CCG CTA GAG GGC TAC TTT AGC

Family History

Perfect Baby Ingredients

ATT GCC TAC CTC GGG CTA ATC CTG AAT CGT CAT GAT CCG TAT

Method

CTG AAT CAG GGT CCG CTA GAG GGC TAC TTT AGC

Family Studies

Genetic Factors

Mouse Models

Curly Tail

Nutrition

Obesity

Nongenetic Factors

Maternal Illness

Medication

The Folic Acid Story • Dietary factors recognised 1970’s • Folic Acid required for new cell formation

The Folic Acid Story • Dietary factors recognised 1970’s • Folic Acid required for new cell formation • MRC Trial 1991

Methyl Transferases Substrate

Methylated Product (eg methylated lipids, proteins, DNA etc)

S-Adenosylmethionine

S-Adenosylhomocysteine Cystathionine

Hydrolase ATP

Cystathionine Synthase (vit B6)

Homocysteine Methionine Synthase (Vit B12)

5-Methyl tetrahydrofolate

5,10 Methylene tetrahydrofolate reductase

Methionine

Tetrahydrofolate

5,10 Methylene tetrahydrofolate Folic Acid

Purines

The Folic Acid Story • Dietary factors recognised 1970’s • Folic Acid (vitamin B9) required for new cell formation • MRC Trial 1991 • Must be taken pre-conception • Now recommended for the general population (0.4mg) • 4mg if :-previously affected child/pregnancy affected by spina bifida

Methyl Transferases Substrate

Methylated Product (eg methylated lipids, proteins, DNA etc)

S-Adenosylmethionine

S-Adenosylhomocysteine Cystathionine

Hydrolase ATP

Cystathionine Synthase (vit B6)

Homocysteine Methionine Synthase (Vit B12)

5-Methyl tetrahydrofolate

5,10 Methylene tetrahydrofolate reductase

Methionine

Tetrahydrofolate

5,10 Methylene tetrahydrofolate Folic Acid

Purines

Inositol • Carbohydrate • Required for a number of signalling and secondary messenger molecules, including gene expression • PONTI Study

Vitamin B12 Irish and Canadian studies have shown that women with low vitamin B12 levels have a higher risk of having a child with a neural tube defect

The Future?

Exome Sequencing