Mechanisms of Inheritance

Autosomal Mendel

Independent assortment

Autosomal Linkage

Genes on same chromosome.

Epistasis

Genes in pathways

Y-Linked

Only males have Y

X-Linked

Males have one X vs females with XX.

X-inactivation

Random X silencing.

Mitochondrial

Mitochondria has its own, small set of dna.

Mitochondrial dna is only passed on from the mother.

• Mitochondria only exists in the egg cell; father does not pass on mitochondrial dna.

Six Modes of Inheritance

Autosomal Dominant Mendel

Affects both genders equally.

Autosomal Recessive

Affects both genders equally.

Y-Linked

Affects only males.

Mitochondrial

Affects all children of an affected mother.

X-Linked Dominant

More likely to affect females because they have two copies of X.

X-Linked Recessive

More likely to affect males because they only have one X chromosome.

Pedigrees

A generation chart.

Circles

Females

Squares

Males

Filled-In

An affected individual.

Instead of guessing at two possible alleles, can use underscore to denote either/or.

Interpreting

Ask

• Are males/females affected evenly?
• Does the affected condition skip generations?
  • If it does, means the condition is most likely recessive.
  • Unaffected generations are likely carries of the condition.
• What are the parent/child relationships?

Hemizygous

Sex gene males only have one X copy.

Step 1: Does sex matter?

• Look at the affected individuals' sexes:
  • If only one sex (predominantly) is affected → Likely X-linked recessive, x-linked dominant OR Y-linked (first check y-linked because you can easily check all father → son transmission)
  • If both sexes equally affected (roughly) → Likely autosomal recessive, autosomal dominant or mitochondrial (first check mitochondrial because you can easily check. Affected mother = all children affected; affected father = no children affected)

Step 2: Does it skip generations?

(Focus on transmission between biologically related people - parents to offspring)

• Skips generations (affected → unaffected → affected):
  • Pattern: Affected grandparent → unaffected parent → affected grandchild
  • This indicates RECESSIVE inheritance
  • Carriers (heterozygotes) don't show the trait
  • Don’t forget to consider generation 1 too!!
• Does NOT skip generations (appears in every generation):
  • Affected individuals in EVERY generations
  • This indicates DOMINANT inheritance
  • Even one copy of the allele causes the trait to appear

Step 3: Check parent-offspring relationships by testing genotypes to confirm the pattern

The genotypes of affected individual are different in dominant vs recessive patterns (versus mitochondrial and y-linked are mostly presence vs absence)

For RECESSIVE patterns:

• Affected genotype
  • Autosomal recessive = aa
  • X-linked recessive = XaXa OR XaY
• Unaffected genotype
  • Autosomal recessive = Aa or AA (aka A_)
  • X-linked recessive = XAXa OR XAXA (aka XAX_) OR XAY

For DOMINANT patterns:

• Affected genotype
  • Autosomal dominant = Aa or AA (aka A_)
  • X-linked dominant = XAXa OR XAXA (aka XAX_) OR XAY
• Unaffected genotype
  • Autosomal dominant = aa
  • X-linked dominant = XaXa OR XaY

The unaffected vs affected genotypes are opposite when comparing dominant and recessive patterns!