Cytogenetics - Lesson 9

Pedigree Analysis and Genetic Counseling

Sheldon Reed in 1947

Person who coined Genetic Counseling

Sheldon Reed

Geneticist who advises physician on how to explain heredity to patients with single-gene diseases

1971

When the first batch of trained genetic counselors were trained

1. Family history of cancer

2. Family history of multifactorial disease

3. Family history of abnormal chromosomes

4. Elevated risk of single-gene disease

Reasons for patient to see a Genetic Counselor

1. Family history assessment

2. Pedigree construction and identifying family members who are at risk

3. Genetic testing (including karyotyping) and discussion of results and treatments

Involvements of Genetic Counseling

Karyotype

Genetic testing technique that tests for abnormalities of chromosomes

Aminocentesis

Genetic testing technique that samples amniotic fluid to screen for abnormalities in a fetus

Pedigree Analysis

Genetic testing technique that determines disease family history

X

In Pedigree Analysis, Genetic Counselor deduce dominance and distinguish autosomal from _-linked inheritance

1. If a trait is dominant or recessive

2. Autosomal or sex chromosome a trait is linked to

3. Genotypes of family members

4. Probabilities of phenotypes in future generations

Analyzing pedigrees can reveal

Males

Squares

Females

Circles

Presence of a trait

Shaded squares or circles

Roman numerals

Rows are generations labeled with ____

Unknown Sex

Triangles

Carrier Female

Circle with Dot

Autosomal Dominant

One mutated allele causes the disease

Autosomal Dominant

Appears in every generation of an affected family (vertical)

Autosomal Dominant

Each affected person usually has one affected parent

Autosomal Dominant

Marfan Syndrome

Autosomal Dominant

Achondroplasia

Autosomal Dominant

Huntington Disease

Autosomal Dominant

Myotonic Dystrophy

Autosomal Recessive

Two mutated alleles cause disease

Autosomal Recessive

Parents are usually unaffected heterozygotes

Autosomal Recessive

Not typically seen in every generation (horizontal)

Autosomal Recessive

Beta Thalassemia

Autosomal Recessive

Cystic Fibrosis

Autosomal Recessive

Homocystinuria

X-Linked Dominant

Females are more frequently affected than males

X-Linked Dominant

No male-to-male transmission

X-Linked Dominant

Rett Syndrome

X-Linked Dominant

Hypophosphatemia

X-Linked Recessive

Males are more frequently affected than females

X-Linked Recessive

Both parents of an affected daughter must be carriers

X-Linked Recessive

Father cannot pass X-linked traits to their sons

X-Linked Recessive

Hemophilia

X-Linked Recessive

Duchenne Muscular Dystrophy

Mitochondrial

Only females can pass on conditions (maternal inheritance)

Mitochondrial

Both males and females can be affected

Mitochondrial

Can appear in every generation of a family

Mitochondrial

Leber’s Hereditary Optic Neuropathy (LHON)

Autosomal Dominant

Approximately half of everybody

Autosomal Recessive and X-Linked Recessive

Rare

Autosomal Recessive

Consanguinity

X-Linked Dominant

Males get it from affected mothers and give it to their daughters

X-Linked Recessive

Males generally get it from unaffected mothers

Y-Linked

All males, all the time, all generations

Mitochondrial

Every child of affected mother is affected

Algorithm

Autosomal Recessive

Tay-Sachs Disease

Autosomal Recessive

Maple Syrup Urine Disease

Phenylketonuria (PKU)

Metabolic disease caused by a mutation in a gene encoding phenylalanine which leads to mental retardation
Autosomal Recessive

Autosomal Dominant

Freckles

Autosomal Dominant

Polydactylism

50 to 60 years

Life expectancy of Huntington Disease

Huntington Disease

Affects central nervous system

X-Linked Recessive

Affected father do not pass disease to their sons

X-Linked Recessive

Defects in enzymatic genes

X-Linked Recessive and Dominant

Presents usually after puberty

Manifesting Heterozygotes

Affected with just one defective copy if normal X chromosome is inactivated to Barr body

X-Linked Recessive

Red-Green Color Blindness

X-Linked Recessive

X-Linked Ichthyosis

X-Linked Dominant

Affected fathers pass to all of daughters but not their sons

X-Linked Dominant

Incontinentia Pigmenti (skin lesions)

X-Linked Dominant

X-Linked Rickets (bones soften or deform)

Holandric Inheritance

Also known as Y-Linked Inheritance

Mitochondrial

Defects in electron transport or oxidative phosphorylation process

Mitochondrial

Presents as neuropathies or myopathies

Mitochondrial

Variable expression due to heteroplasmy