Mendelian Pedigree patterns

• Autosomal dominant

• Autosomal recessive

• X-Linked recessive

• X-linked dominant

• Y-linked

Autosomal dominant (3.2A)

• Marfan’s syndrome, Neurofibromatosis, Huntington Disease, Retinoblastoma

• An affected person usually has at least one affected parent.

• Affects either sex.

• Transmitted by either sex.

• A child of affected x unaffected mating has a 50% chance of being affected.

Autosomal recessive (3.2B)

• Cystic fibrosis, Phenylketonuria, Tay-Sachs• Affected people are usually born to unaffected

parents.• Parents of affected people usually asymptomatic

carriers.• There is an increased incidence of parental

consanguinity.• Affects either sex.• After birth of an affected child each subsequent

child has 25% chance of being affected.

X-linked recessive (3.2C)

• Hemophilia, Lesch-Nyhan• Affects mainly males.• Affected males are usually born to

unaffected parents; the mother is typically an asymptomatic carrier and may have affected male relatives.

• Females may be affected if father is affected and mother is a carrier.

• No male to male transmission.

X-linked dominant (3.2D)

• Vitamin D resistant rickets.• Affects either sex, but more females than males.• Females are often more mildly and more

variably affected than males.• The child of an affected female, regardless of

sex, has a 50% chance of being affected.• For an affected male, all daughters and no sons

are affected.

Y-linked inheritance (3.2E)

• Affects only males.

• Affected males always have an affected father unless there is a new mutation.

• All sons of an affected man are affected.

Mitochondrial diseases

• Typical pattern for hearing loss.

• Atypical Leber’s hereditary optic atrophy.

Complications to basic pedigrees

• Typical pattern for blood group O (3.13).• AD with nonpenetrance in II2 (3.14).• AD with variable expression (3.17).• Genetic imprinting (3.18).• X-linked dominant incontinentia pigmenti (3.19).• X-linked recessive with inbreeding (3.20).• A new AD mutation, mimicking recessive (3.21).

Complications to basic pedigrees

• Typical pattern for blood group O (3.13).– Appears as a dominant pattern

Complications to basic pedigrees

• AD with nonpenetrance in II2 (3.14).

Complications to basic pedigrees

• AD with variable expression (3.17).– Waardenburg syndrome– Shading 1st quad = hearing loss– Shading of 2nd quad = different colored eyes– Shading of 3rd quad = white forelock– Shading of 4th quad = premature graying of

hair

Complications to basic pedigrees

• Genetic imprinting (3.18).– AD glomus tumors manifest only when gene s

inherited from father (A).

– AD Beckwith-Wiedemann syndrome manifests only when gene is inherited from mother (B).

Complications to basic pedigrees

• X-linked dominant incontinentia pigmenti (3.19).– Affected males abort spontaneously.

Complications to basic pedigrees

• X-linked recessive with inbreeding (3.20).– Inbreeding gives an affected female and

apparent male to male transmission.

Complications to basic pedigrees

• A new AD mutation, mimicking recessive (3.21).

Huntington Age of Onset

• Probability that an individual carrying the disease gene will have developed symptoms by a given age (A).

• Risk that a healthy child of an affected parent carries the disease gene at a given age (B).

New Mutation in X-linked recessive DMD

• III1 has the grandparental X which acquired a mutation at some point.– III1 caries a new mutation– II1 is a germinal mosaic (risk for children, but

not sisters)– II1 was the result of a single mutation,

standard recurrence risk or X-linked recessives, sister free of risk.

– I1 was a germinal mosaic, all the sisters have a significant risk, which is hard to quantify.

Germinal Mosaic

• AD adenomatous polyposis– Normal = bottom band, mutant = upper bands

– Females II2 and II3 are carriers of high risk allele.

– High risk chromosome is blue, II2 shows mosaic expression while III4 does not.

Hardy-Weinberg Law

• p2 + 2pq + q2 = 1.0

• p + q = 1.0

Incidence

• Autosomal recessive– q2

• Autosomal dominant– p2 + 2pq

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