spina bifida and genetics by margo whiteford

Spina  Bifida  and  Gene,cs  

Margo  Whiteford  President  IF  

What  Is  A  Gene?  

DNA  

What  Is  A  Gene?  

‘A  recipe  for  the  produc,on  of  proteins  used  in  the  forma,on  and  the  func,on  of  the  body  as  it  goes  throughout  life’  

Chromosomes  

Gene,c  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  

Gene,c  Factors  

Non-­‐gene,c  Factors  

Mul,factorial  

Gene,c  Factors  

What  Are  The  Gene,c  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  

Gene,c  Factors   Mouse  Models  

Family  Studies  

Curly  Tail  

Non-­‐gene,c  Factors  

Nutri,on   Maternal  Illness  

Obesity   Medica,on  

The  Folic  Acid  Story  

•  Dietary  factors  recognised  1970’s  •  Folic  Acid  required  for  new  cell  forma,on    

The  Folic  Acid  Story  

•  Dietary  factors  recognised  1970’s  •  Folic  Acid  required  for  new  cell  forma,on    

Methylated  Product  

(eg  methylated  lipids,  proteins,  DNA  etc)  

Substrate  

Methyl  Transferases  

S-­‐Adenosylmethionine  

ATP  

Methionine  

Tetrahydrofolate  

Folic  Acid  

Purines  

5,10  Methylene  tetrahydrofolate  reductase  

5-­‐Methyl  tetrahydrofolate  

Homocysteine  

Hydrolase  

S-­‐Adenosylhomocysteine  

Cystathionine  Synthase  (vit  B6)  

Cystathionine  

5,10  Methylene  tetrahydrofolate  

Methionine  Synthase  (Vit  B12)  

The  Folic  Acid  Story  

•  Dietary  factors  recognised  1970’s  •  Folic  Acid  required  for  new  cell  forma,on  •  MRC  Trial  1991    

The  Folic  Acid  Story  

•  Dietary  factors  recognised  1970’s  •  Folic  Acid  (vitamin  B9)  required  for  new  cell  forma,on  

•  MRC  Trial  1991  •  Must  be  taken  pre-­‐concep,on  •  Now  recommended  for  the  general  popula,on  (0.4mg)  

•  4mg  if  :-­‐  previously  affected  child/pregnancy                    affected  by  spina  bifida  

Methylated  Product  

(eg  methylated  lipids,  proteins,  DNA  etc)  

Substrate  

Methyl  Transferases  

S-­‐Adenosylmethionine  

ATP  

Methionine  

Tetrahydrofolate  

Folic  Acid  

Purines  

5,10  Methylene  tetrahydrofolate  reductase  

5-­‐Methyl  tetrahydrofolate  

Homocysteine  

Hydrolase  

S-­‐Adenosylhomocysteine  

Cystathionine  Synthase  (vit  B6)  

Cystathionine  

5,10  Methylene  tetrahydrofolate  

Methionine  Synthase  (Vit  B12)  

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