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