[CYTOGENETICS] Pedigree Analysis

Sheldon Reed

In 1947, "Genetic counseling" was coined by ________, a geneticist who advises physician on how to explain heredity to patients with single-gene diseases

Thyroid Cancer

Fast to diagnose and manage

Karyotyping Amniocentesis

Genetic Testing technique

15-20th week of pregnancy

Week to do Amniocentesis and Karyotyping

If beyond this, the volume of the fluid may not be enough

Beyond this, the fetus may be at risk of injury; Beyond this, too late to act on the detected fetal problem

Pedigree Analysis

Genetic analysis method to determine disease family history

Genetic counselor deduce dominance and distinguish autosomal from X-linked inheritance

True

T/F;

The clues in the pedigree have to be interpreted differently depending on whether one of the contrasting phenotypes is a rare disorder or whether both phenotypes of a pair are common morphs of a polymorphism

Pedigree Chart

Family tree, with standard genetic symbols

Shows inheritance patterns

Autosomal Dominant

One mutated allele causes the disease Each affected person usually has one affected parent Appears in every generation of an affected family (Vertical)

Marfan syndrome

Achondroplasia

Huntington disease

Myotonic dystrophy

Autosomal Recessive

Two mutated alleles needed to cause the disease Parents are usually unaffected heterozygotes Not typically seen in every generation (Horizontal).

Beta thalassemia

Cystic fibrosis

Homocystinuria

X-linked Dominant

Females are more frequently affected than males no male-to-male transmission

Rett syndrome

Hypophosphatemia

X-linked Recessive

Males are more frequently affected than females

Both parents of an affected daughter must be carriers. Fathers cannot pass X-linked traits to their sons

Hemophilia

Duchenne Muscular Dystrophy

Mitochondrial

Only females can pass on mitochondrial conditions to their children (maternal inheritance)

Both males and females can be affected

Can appear in every generation of a family

LHON: Leber's hereditary optic neuropathy

Y-linked inheritance pattern

Trait is always passed from father to son without skipping a generation

Mitochondrial inheritance

The trait is passed from generation to generation

No skipping of generation

Mom → both children (male or female)

Autosomal

The trait is located between Chromosomes 1 to 22

X-linked

A trait found in the X chromosome

Autosomal Dominant

Approximately half of everybody

Males and females affected

All generations

Autosomal Recessive

Rare

Skips generations

Males and females affected

Consanguinity 0=O

X-linked dominant (sex-linked dominant)

Some females can have it

All generations (no skipped generations)

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

X-linked recessive (sex-linked recessive)

Rare

Males predominantly have it

Generally skips generations

Males generally get it from unaffected mothers

Y-linked

All males, all the time, all generations (must be direct descendent of the family)

Mitochondrial or Maternal

Every child of affected mother is affected

AUTOSOMAL RECESSIVE TRAIT

Traits caused by genes on autosomes and requiring two allele copies to influence a phenotype are autosomal recessive.

AUTOSOMAL RECESSIVE TRAIT

Several disorders are autosomal recessive, including cystic fibrosis, Tay-Sachs disease, and maple syrup urine disease

AUTOSOMAL RECESSIVE TRAIT

Most people with these diseases have heterozygous parents who do not have the condition but carry a causal allele

AUTOSOMAL RECESSIVE TRAIT

Most people with these diseases have heterozygous parents who do not have the condition but carry a causal allele.

AUTOSOMAL RECESSIVE TRAIT

These carriers can unknowingly impart the disease to their children, which partially explains why autosomal recessive diseases are more common than their dominant counterparts.

AUTOSOMAL RECESSIVE TRAIT

Comparing generations on a pedigree can reveal whether an autosomal trait is dominant or recessive. Neither parent has the trait, but one child inherits it. Thus, it must be recessive

PHENYLKETONURIA

A human metabolic disease caused by a mutation in a gene encoding a phenylalanine- processing enzyme, which leads to mental retardation if not treated; inherited as an autosomal recessive phenotype.

AUTOSOMAL DOMINANT TRAIT

These are requiring only one copy of the determining allele to influence phenotype

Freckles and polydactylism (extra fingers or toes) are examples

Such as Huntington's disease, afflict ~50% of offspring with one affected parent.

AUTOSOMAL DOMINANT TRAIT

Many of these diseases do not cause symptoms until later in life and or after reproductive age.

AUTOSOMAL DOMINANT TRAIT

Children can inherit these diseases from unknowingly affected parents, highlighting the importance of analyzing family history

HUNTINGTON'S DISEASE

an autosomal dominant genetic disorder that affects the central nervous system of human beings.

This disease typically shows up when a person reaches their mid 30's or 40's, with no earlier signs or symptoms.

The nerve cells of an affected individual quickly degenerate in certain parts of the brain, which leads to symptoms that include dementia, loss of memory, and severely decreased mental capacity, muscle rigidity, and loss of bodily function and muscle coordination.

Usually shortens an affected persons lifespan, with the average person dying 15-20 years after onset of the disease, making the life expectancy around 50-60 years of age

X-LINKED RECESSIVE

The trait is rare in a pedigree.

Trait skips generations.

Affected fathers DO NOT pass to their sons.

Males are more often affected than females

X-LINKED RECESSIVE

Genders affected

males must receive defective gene from carrier mother

carrier mother's sons have 50% of having disease

affected males give copy to all of their daughters

X-LINKED RECESSIVE

Hemophilia

X-LINKED RECESSIVE

Red-green color blindness

Hemophilia

X-linked ichthyosis

X-LINKED DOMINANT

Trait is common in pedigree.

Affected fathers pass to ALL of their daughters, but not their sons

Does not skip generations

Genders affected (male and female at equal frequency)

Y-LINKED INHERITANCE

Inheritance of genes on the Y chromosome

Since only males normally have a Y chromosome, Y-linked genes can

only be transmitted from father to son

Also called holandric inheritance

MITOCHONDRIAL

Genders affected - male and females at equal frequency

Generations affected - does not skip generations

Pathology

> defects in electron transport/oxidative phosphorylation process

> presents as neuropathies/myopathies

> neurons and muscle cells require high amounts of energy and depend on mitochondria

Autosomal recessive inheritance

X-linked recessive

Autosomal Dominant

Autosomal Recessive

X-linked recessive

Mitochondrial Dominant

Y-Linked Dominant