L27 Single Gene Disorders Flashcards
Define ‘consanguineous’.
People descended from the same ancestor.
A genetic study on a large consanguineous Pakistani family with a family history of Familial hypercholesterolemia (FH) identified what?
A common insertion mutation was identified in exon 17 of the LDLR gene.
c.2416_2417InsG
Familial Hypercholesterolemia is an example of what type of point mutation?
Insertion mutation
Cystic fibrosis is an example of what type of point mutation?
Deletion mutation
The majority of cystic fibrosis patients in Western Europe harbour a deletion mutation. What is this mutation?
Phenylalanine (F) is deleted from position 508 in the protein. UUU codon CFTR gene on chr 7.
What causes Duchenne Muscular Dystrophy?
A deletion mutation in an intron induces aberrant splicing of the DMD gene - causing Duchenne Muscular Dystrophy.
What is a homozygote?
An individual with 2 identical alleles for a specific trait.
What is a heterozygote?
An individual 2 different alleles for a specific trait.
Define ‘autosomal’.
Refers to the 44 non-sex chromosomes.
How can you tell whether or not an autosomal gene is dominant?
Look at the family tree: if all affected children have an affected parent then you know it is dominant. If not, it is recessive.
How can you tell whether or not an autosomal dominant gene is X-linked or not?
If affected males all have affected mothers, or affected females all have affected fathers then it is X-linked. Otherwise, it is not X-linked.
What is the chance of inheriting an autosomal dominant gene?
1 in 2
True or false: Recessive gene inheritance can produce an affected individual born to unaffected parents.
True
Why can’t males inherit X-linked mutations from their father?
Because males always receive the Y chromosome from their father.
In what type of mutation is the characteristic not manifested in a heterozygote?
Recessive mutations
Males pass on X-linked mutations to their __?__
Daughters
Females pass on X-linked mutations to their __?__
Sons and daughters
Define ‘genetic heterogeneity’.
Different mutation in the same gene can lead to different diseases
What condition is caused by the following mutation?
FGFR-3 Gene
P250R
(P=proline, R=arginine)
Muenke’s syndrome
What condition is caused by the following mutation?
FGFR-3 Gene
G308R
(G=glycine, R=arginine)
Achondroplasia
Achondroplasia is caused by a ‘gain of function’ mutation.
Explain how this causes stunted growth in affected patients.
Mutation in the FGFR3 gene (fibroblast growth factor receptor (type 3)) promotes unregulated conversion of cartilage to bone - growth plates ossify prematurely, limiting growth.
What is xeroderma pigmentosum (XP)?
Mutations in any of 8 different genes that affect DNA-damage repair.
Causes hypersensitivity to sunlight, often resulting in carcinomas.
In addition to the mutation, what other factors influence the phenotype of single gene disorders?
Penetrance (determined by genetic and environmental factors)
Expressivity (variance in the severity of the symptoms)
Phenocopy (environmental modification mimics genetic disease)
Environmental effects
What is phenylketonuria?
A genetic disease that means phenylalanine cannot be broken down by the body. But it can be regulated by maintaining a low phenylalanine diet.
Example of how environmental factors affect the phenotype of single gene disorder
