18 Mendelian Inheritance in Humans Flashcards
What is a Mendelian/monogenic disease?
Only one gene is involved
What is a multifactorial disease?
Many genes are involved
How many Mendelian characters are known in humans?
Over 6000
Not all are diseases
What are the uses of pedigrees?
- To infer mode of inheritance
- Genetic counselling
How are males and females shown on pedigrees?
Females - Circle
Males - Square
Sex unknown - Diamond
What are the 5 basic mendelian patterns?
Autosomal dominant
Autosomal recessive
X-linked recessive
X-linked dominant
Y-linked - no opportunity for dominant or recessive
What are the characteristics of an autosomal dominant disease?
- Affected person usually has at least one affected parent
- Affects and transmitted by either sex
- 50% chance a child gets disease between unaffected + affected (heterozygous) parents
What are examples of autosomal dominant phenotypes?
Achondroplasia - form of dwarfism
Polydactyly
Hairy mid-digit
Widow’s peak
Mendel’s peas
What are the characteristics of an autosomal recessive disorder?
- Affected offspring usually have unaffected parents that are carriers
- Affects either sex
- Often in pedigrees with inbreeding
- 1/4 chance of being affected and 1/2 chance of being carrier if both parents carriers
What are examples of autosomal recessive conditions?
Albinism
Sickle cell anaemia
Cystic fibrosis
Attached ear lobes
What is cystic fibrosis?
Most common autosomal recessive condition in Europeans
- Affects lungs - increased mucus secretion
- Median survival ~50 years
Why might the CF allele have been advantageous in the past?
Heterozygotes for cystic fibrosis may have had a selective advantage through resistance to cholera, typhoid or other diseases
What causes cystic fibrosis?
Affected people have two inactive copies of the CFTR gene
Δ 508 mutation results in a 3bp deletion and a non-functional protein - chloride channel
What are the characteristics of X-linked recessive disorders?
- Affects mainly males
- 0.5 probability that male offspring from a female carrier will be affected
- Females only affected if father affected and mother is carrier
- Often linked through maternal lines of the family
What are examples of X-linked recessive disorders?
Duchenne muscular dystrophy
Red-green colour blindness
Haemophilia
What are the characteristics of X-linked dominant disorders?
- Affect either sex
- Affected males always have affected female offspring but no affected male offspring
Why are there very few examples of X-linked dominant disorders?
e.g. Hypophosphatemia
- Vit D resistant rickets
Selection is very good at removing these disorders from the population
What is X chromosome inactivation?
In each cell of females one X is randomly inactivated
- Occurs early in development
- Daughter cells have the same X inactivated
What are the characteristics of Y-linked disorders?
- Affects only males
- All sons of an affected man are affected
