TOPIC 26: Inheritance Patterns – Recognize Various Inheritance Patterns
OFFICIAL ABP TOPIC:
Recognize various inheritance patterns
BACKGROUND
Understanding inheritance patterns is essential for recognizing genetic disorders, diagnosing affected individuals, and providing accurate genetic counseling to families. Inheritance patterns describe how genetic traits or diseases are passed from parents to offspring.
MENDELIAN INHERITANCE PATTERNS
Mendelian inheritance describes traits caused by single-gene variants that follow predictable patterns of inheritance.
|
INHERITANCE PATTERN |
KEY FEATURES |
CLUES FOR RECOGNITION |
EXAMPLES |
|
Autosomal Dominant |
50% risk for offspring of affected parent |
Multiple generations affected |
Huntington disease, Marfan syndrome, familial hypercholesterolemia |
|
Autosomal Recessive |
25% risk for offspring of two parents who are unaffected carriers |
Skips generations; consanguinity more common |
Cystic fibrosis, sickle cell anemia, phenylketonuria |
|
X-Linked Recessive |
Male predominance; carrier females may show mild symptoms |
No father-to-son transmission; affected males born to carrier mothers |
Hemophilia A and B, Duchenne muscular dystrophy, red-green color blindness, G6PD deficiency |
|
X-Linked Dominant |
Males often more severely affected; all daughters of affected fathers inherit the trait |
Females more commonly affected than males |
Rett syndrome, vitamin D-resistant rickets, X-linked hypophosphatemic rickets |
|
Y-Linked |
Only males affected; father transmits to all sons |
Rare; associated with male infertility |
Azoospermia |
NON-MENDELIAN INHERITANCE PATTERNS
Non-Mendelian inheritance patterns deviate from classic Mendelian laws due to unique mechanisms.
|
PATTERN |
MECHANISM |
CLUES FOR RECOGNITION |
EXAMPLES |
|
Mitochondrial |
Variants in mitochondrial DNA; inherited exclusively from mother |
Maternal transmission only; variable severity due to heteroplasmy |
MELAS syndrome, Leber hereditary optic neuropathy, maternally inherited deafness |
|
Anticipation |
Trinucleotide repeat expansions in causative genes |
Earlier onset or increasing severity in successive generations |
Myotonic dystrophy, Fragile X syndrome, Huntington disease |
|
Genomic Imprinting |
Parent-specific gene silencing due to epigenetic modifications (e.g., DNA methylation) |
Phenotype depends on parent of origin |
Prader-Willi syndrome (paternal), Angelman syndrome (maternal), Beckwith-Wiedemann syndrome |
|
Mosaicism |
Post-fertilization mutations lead to genetically distinct cell populations |
Milder or segmental phenotypes; apparent lack of family history |
McCune-Albright syndrome (somatic), hemophilia A (germline), Proteus syndrome |
RECOGNIZING INHERITANCE PATTERNS
1. Obtain family history:
- Construct a 3-generation pedigree.
- Identify patterns of affected individuals across generations.
2. Identify clues for inheritance:
- Affects successive generations with 50% of offspring → Likely autosomal dominant.
- Parents healthy but 25% of offspring affected → Suggests autosomal recessive.
- Male predominance → Consider X-linked recessive.
- Affected father passes trait to all daughters → Suggests X-linked dominant.
- Affected mother passes trait to all offspring → Consider mitochondrial transmission.
- Increasing severity in successive generations → Possible anticipation.