Inheritance Patterns

What are these symptoms of?

Short, webbed neck

Decreased range of motion in the cervical spine

Low-set hairline

Klippel-Feil Syndrome

What Klippel-Feil Syndrome characterised by

congenital fusion of any 2 of the 7 cervical vertebrae

What causes Klippel-Feil Syndrome

Mutations in the GDF6, GDF3, or MEOX1 genes

Is Huntington Disease inherited in an autosomal dominant/recessive pattern

Dominant

Huntington Disease Symptoms

Progressive neuronal loss - disease onset usually occurs in 30’s or 40’s

Huntington Disease cause

mutation in the HTT gene (a repeat - the more repeats, the earlier the onset or more severe phenotype)

• 27-35 premutation (risk for children)

• 36-39 at risk (incomplete penetrance)

• 40+ = HD

Select the non-hereditary, congenital diseases from the following list:

• Cystic Fibrosis

• Toxoplasmosis

• Sickle Cell Anaemia

• Cerebral Palsy

• Type 1 Diabetes

Toxoplasmosis

Cerebral Palsy

Rank these concepts in order of first appearance

• The concept of DNA

• The concept of genes

• The concept of inheritance

The concept of inheritance

The concept of genes

The concept of DNA

Autosomal inheritance

Not sex dependent

(Allele located on one of the 22 autosomes)

What does each symbol mean on a pedigree chart

Finding out the pattern of inheritance, what 2 questions must you ask?

Are the parents affected/carriers?

Does it affect both genders?

What pattern of Mendelian Inheritance is this?

Autosomal Dominant

What pattern of Mendelian Inheritance is this?

Sex linked mendelian inheritance

What is a dichotomous trait

Yes/No - You have it or you don’t

What is a Polygenic/Multifactorial trait

Character is determined by a large number of genes and the interaction of expression of those genes with the environment (not Mendelian)

Give examples of dichotomous traits

Height

Shoe size

Eye colour

Intelligence

Incomplete penetrance

Penetrance = probability of a genotype/trait being expressed

Incomplete = phenotype only expressed in a fraction (%) of the population with the genotype

Variable expressivity

Variation in phenotypic expression when penetrance is complete

A range of symptoms displayed in individuals with the same fully penetrant genotype

Variable expressivity is the norm among genetic diseases and is particularly common for disorders that affect multiple organ systems

Clinical Case (Osteogenesis imperfecta (OI))

Rachel’s mother had 10 leg bone fractures as a child, is 4ft 11 inches tall, is very double-jointed and has had blue/grey sclera since birth

Rachel is 26, 5 ft 7, has never had a fracture and has normal colour eyes

Rachel’s daughter is 4, has already had 2 fractures, is slightly double-jointed and has normal colour eyes

All three females are heterozygous for the same dominant mutation in the COL1A1 gene.

What phenomenon best explains the genotype phenotype correlation seen in Rachel?

Incomplete penetrance

Clinical Case (Osteogenesis imperfecta (OI))

Rachel’s mother had 10 leg bone fractures as a child, is 4ft 11 inches tall, is very double-jointed and has had blue/grey sclera since birth

Rachel is 26, 5 ft 7, has never had a fracture and has normal colour eyes

Rachel’s daughter is 4, has already had 2 fractures, is slightly double-jointed and has normal colour eyes

All three females are heterozygous for the same dominant mutation in the COL1A1 gene.

What phenomenon best explains the genotype-phenotype correlation seen between Rachel’s child and her grandmother?

Variable expressivity

Familial Hypercholesterolemia, is a genetic disorder with a dominant pattern of inheritance that is associated with mutations in the LDLR gene on Chr19

Roberto 35 - Heterozygous for LDLR mutation

Elevated LDL cholesterol 350mg/dL

Skin lesions (xanthelasmata) present on eyelids and under the eyes

Recently had a mild MI

His twin sons (age 2) have symmetrical xanthomas on their knees and elbows

Blood LDL cholesterol level 1.2g/dL

Homozygous for LDLR mutation

What phenomenon of inheritance explains the phenotype of Roberto’s condition?

Congenital

Present at birth.

(Not necessarily hereditary)