Clinical Genetics Inheritance Patterns

Question 1

Genetic Variability

Answer 1

Genetic Variability are the differences in degree of the phenotype produced by the same genotype
**Evaluated with familial studies (twin studies)

Question 2

Incomplete or Partial Penetrance

Answer 2

Incomplete or Partial penetrance is a mutation which does not produce a mutant phenotype in everyone who inherits the mutant genotype
**any symptoms or no symptoms- not severity of symptoms. all or nothing

Question 3

Multifactorial Traits

Answer 3

Multifactorial Traits are phenotypes that are determined by multiple factors, both genetic and environmental

Question 4

Polygenic Traits

Answer 4

Polygenic traits are phenotypes that are determined by multiple genes

Question 5

Heterogeneity

diseases:

Answer 5

Heterogeneity are mutations of different genes and/or alleles that produces the same disease
diseases: cystic Fibrosis, Osteogenesis Imperfecta, SCIDS, Ehlers-Danlos Syndromes, Thalisemias, Congenital Deafness

Question 6

Pleiotropy

diseases:

Answer 6

Pleiotropy is a single gene that controls multiple traits

Cystic Fibrosis, Phenylketonuria, Hurler Syndrome, Achondroplasia, Neurofibromatosis

Question 7

polymorphism

Examples:

Answer 7

Polymorphism- multiple alleles for a gene in a population, eaach with an allelic frequency (q) above 5%
Example: Blood Groups (have alleles for A, B, or none)

Question 8

Marfan Syndrome
inheritance pattern:
mutations in _______ gene
Symptoms:

Answer 8

Marfan Syndrome
inheritance pattern: AD
mutations in fibrillin gene
Symptoms: Long and thin extremities, tall stature, arachnodactyly, myopia, aortic root dilation (risk for aortic aneurysms)

Question 9

Neurofibromatosis 1 (NF1)
gene product:
symptoms:

Answer 9

Neurofibromatosis is an example of pleiotropy (a single gene that controls multiple traits). It has the highest mutation rate observed in humans
NF1
gene product: neurofibromin
symptoms: neurofibromas. They can be sessile or pedunculated hyperpigmented Macules (Cafe Au Lait Spots)

Question 10

Codominance

Answer 10

Codominance are different alleles inducing independent effects on the phenotype
Example: Blood Groups

Question 11

Mitochondrial Inheritance:
Heteroplasmy-
Examples

Answer 11

Mitochondrial inheritance- Maternal inheritance- transmission from mothers to all children regardless of sex, never transmitted from fathers to any children.
Heteroplasmy- mixed intracellular populations of mitochondria with mutant and wild type genomes (symptoms can vary from generation to generation or during the lifetime of an individual)
Examples of Mitochondrial Inheritance:
LEBER HEREDITARY OPTIC NEUROPATHY (NADH dehydrogenase) blindness, Telangiectatic microangiopahy, vascular tortuosity
KEARN-SAYRE SYNDROME- (ox-phos complex genes) Retinal degeneration, Heart block, Short stature, diabetes, deafness, thyroid disease

Question 12

Anticipation

examples

Answer 12

A mutant phenotype that increases in severity each generation
Trinucleotide repeat expansion: Fragile X syndrome, Huntington, Myotonic Muscular Dystrophy

Question 13

Fragile X:
repeat:
normal:
affected:
inheritance:

Answer 13

Fragile X:

repeat: CGG
normal: 6-50
affected: 200+
inheritance: XD

Question 14

Huntington:
repeat:
normal:
affected:
inheritance:

Answer 14

Huntington:

repeat: CAG
normal: 6-35
affected: 36-120
inheritance: AD

Question 15

Myotonic Muscular Dystrophy
repeat:
normal:
affected:
inheritance:

Answer 15

Myotonic Muscular Dystrophy:

repeat: CTG
normal: 5-35
affected: >200
inheritance: AD

Question 16

Epigenic Imprinting

examples:

Answer 16

Epigenic Imprinting- a mutant genotype with a different phenotype depending on context (e.g. the sex of the patient)
Prader-willi and angelman Syndrome

Question 17

Prader-Willi Syndrome

Answer 17

Prader-Willi Syndrome: microdeletion on chromosome 15 from the father
Characterized by obesity, almond shaped eyes, hypopigmentation, behavior problems, hypogonadism

Question 18

Angelman Syndrome

Answer 18

Angelman Syndrome: Microdeletion on chromosome 15 from the MOTHER
characterized by: happy disposition, severe mental retardation, jerky and ataxic gate (puppet-like movement), elfin like features, absent speech

Question 19

What is genomic imprinting?

Answer 19

genomic imprinting is methylation of certain genes. the methylation prevents expression of the gene or portion of the gene.