Genetics E1- Patterns of Inheritance

Which pattern of inheritance?

• manifests in heterozygous state

• vertical pattern affects multiple generations

• confirmed w/ male to male transmission

Autosomal Dominant

What are examples of autosomal dominant conditions?

Neurofibromatosis type 1, huntingtons, marfans

With an autosomal dominant condition, what are the chances that the offspring would have the affected phenotype if an affected person mates with an unaffected person?

50%

What term refers to the difference in clinical manifestations between individuals in autosomal dominant disorders? (some have mild dz, some have severe)

Variable expressivity

What occurs when some individuals with a disease causing genotype do not develop the disease phenotype at all?

Reduced penetrance

What term describes an individual who carries the disease gene but shows no clinical features of the condition?

Non-penetrance

What is the proportion of people with a specific genotype who manifest a particular clinical characteristic or phenotype, expressed as a percentage?

Penetrance

What kind of pedigree pattern is observed with autosomal recessive inheritance?

Horizontal; only 1 generation affected; M=F

With an autosomal recessive condition, what are the chances that the offspring would be affected if both parents are asymptomatic, heterozygous carriers?

25% chance of being affected, 25% chance of inheriting neither mutant allele, and 50% chance of being an asx carrier

With an autosomal recessive condition, what are the chances that the offspring would be affected if one parent is affected and one parent is a carrier?

50% will be affected, 50% will be carriers

With an autosomal recessive condition, what are the chances that the offspring would be affected if both parents are affected?

100% will be affected

With an autosomal recessive condition, what are the chances that the offspring would be affected if one parent is affected and one is an unaffected non carrier?

100% will be asymptomatic carriers

What term refers to a recessive trait that mimics dominant transmission?

Pseudodominance

When does pseudodominance occur?

One parent is affected / homozygous recessive (aa) & one parent is asx carrier / heterozygous (Aa) → 50% offspring affected, 50% asx carriers

What term refers to mating between persons biologically related as second cousins or greater, which therefore increases the likelihood of having 2 copies of a harmful allele?

Consanguinity

What type of inheritance?

• carried on X chromosome

• usually manifests only in males

• transmitted from carrier females to their sons → affected males transmit to carrier daughters

X-linked recessive inheritance

If a male with an X-linked recessive condition has offspring, who would be at risk for inheriting the same condition?

Male grandchildren through carrier daughters

What is an example of an X-linked recessive condition?

Duchenne muscular dystrophy

What type of inheritance?

• heterozygous females & males w/ variant allele on their single X chromosome manifest the disease

• no father to son transmission

• F > M

X-linked dominant inheritance

What are examples of X-linked dominant conditions?

Rett syndrome, x-linked hypophosphatemia (vitamin D resistant rickets)

With an X-linked dominant condition, which offspring would be affected if the father has the condition?

100% of daughters, 0% of sons

With an X-linked dominant condition, which offspring would be a affected if the mother has the condition?

50% of daughters, 50% of sons

What type of inheritance?

• only males affected

• affected males must transmit to their sons

• H-Y histocompatibility antigen

Y-linked inheritance / Holandric inheritance

How is mitochondrial DNA inherited?

Exclusively transmitted through the maternal line (mitochondria comes exclusively from the egg during conception)

Which has a higher rate of spontaneous variation, mitochondrial DNA or nuclear DNA?

Mitochondrial DNA

What is homoplasmy?

mtDNA is identical across different mitochondria (MC)

What is heteroplasmy?

2 populations of mtDNA exist due to a variant in the mtDNA of an individual

What type of inheritance consists of disorders that demonstrate familial clustering but don’t have a recognized pattern of mendelian inheritance?

Ex: DM, cancer, CAD, mental health diseases

Multifactorial inheritance

What are genome-wide association studies?

Models showing certain disease states are caused by multiple “bad” genes & adverse environmental factors (T2DM, schizophrenia, RA, etc)