mendelian

describes a trait that is    attributable to a single nuclear gene

      ( A single gene disorder is a disorder                   

            due to one or a pair of mutant

                alleles at a single locus. )              

Compound Heterozygote

-individual or genotype having two different mutant alleles at the same locus

Autosomal Recessive 

Usual occurrence/recurrence risk: 25%.

- Transmission pattern: horizontal.

   Affecteds seen in sibs, not earlier

   generations

- Sex ratio: males and females equally

   affected.

- Consanguinity sometimes a factor. 

Homozygotes for AD conditions

- Homozygotes are usually more severely

  affected

- Some produce lethals

ex. Familial hypercholesterolemia

Five waysDominant mutations have effects :

- a gain of function : increased gene dosage,

  e.g., a duplication; or prolonged protein

  activity (slower degradation)

- a loss of function: haploinsufficiency

- the protein’s acquisition of toxic effects

- the protein’s acquisition of a new function

- a dominant negative effect

Haploinsufficiency

- results when there is a mutation of one allele and the contribution of the normal allele is insufficient to prevent disease.

ex. Waardenburg Syndrome

                    dominant negative    

A disease causing allele which  disrupts the function of the  normal allele in the same cell; seen, for example, in collagen mutations in osteogenesis imperfecta

Autosomal Dominant 

- Usual occurrence/recurrence risk: 50%.

- Transmission pattern: vertical. Affecteds

   seen in multiple generations.

- Sex ratio: males and females equally

   affected.

- Father-son transmission of trait is seen.

X-Linked Dominant Inheritance

gain of a new function

a1-antitrypsin:

     Normally an inhibitor of elastase

     Point mutation at position 358 causes the molecule to be an inhibitor of thrombin.

     Result: severe bleeding disorder