Chromosones Abberation: disorder characterized by a morphological or numerical alteration in single or multiple chromosomes, affecting autosomes, sex chromosomes, or both

Normal: Euploid Cells

Abnormal

• Aneuploidy
• Is a somatic cell that does not contain a multiple of 23 chromosomes.
• Trisomy
• Is a cell that contains three copies of one chromosome, can survive.
• Example: Down Syndrome (aka Trisomy 21)
• Monosomy
• Is the presence of only one copy of any chromosome.
• Example: Turner Syndrome (aka XO)

What is an example of Trisomy

• Trisomy
• Is a cell that contains three copies of one chromosome.
• Example: Down Syndrome (aka Trisomy 21)

What is an example of Monosomy ?

Characterisitics?

• “sTerile”
  Females have only one X chromosome
• Turner Syndrome
• Characteristics include: absence of ovaries (sterile), short stature, webbing of the neck, widely spaced nipples, high number of spontaneously aborted fetuses, X chromosome that is usually inherited from the mother
• Occurs 1 in 2500 female births
• Teenagers receive estrogen.

Sex Chromosome Aneuploidy: Klinefelter Syndrome?

Chromosome?

Appearance?

What population is at increase risk?

• Individuals with at least one Y and two X chromosomes
• Characteristics include: male appearance, female like breasts (gynecomastia), small testes, sparse body hair
• 1 in 1000 male births
• Some individuals can be XXXY and XXXXY; will have male appearance; abnormalities will increase with each X; can also have an extra Y chromosome
• Disorder increases with the mother’s age

Abnormalities of Chromosomal Structure: Cri Du Chat

• disease is caused by a deletion of part of the short arm of chromosome 5
  • only 10% inheritance
• Means “cry of the cat” and describes the characteristic cry of the affected child.
• Other symptoms include:
  • low birth weight
  • severe intellectual disability
  • microcephaly (smaller than normal head size)
  • heart defects.

Elements of Formal Genetics

• The mechanisms by which an individual's set of paired chromosomes produces traits are the principles of genetic inheritance
• Explains the patterns of inheritance for traits and diseases that appear in families
• Traits caused by single genes are called mendelian traits
• Locus: Is the location occupied by a gene on a chromosome.
• Allele: Is one of several different forms of a gene at a locus.
  • an individual has one allele whose origin is paternal and one whose origin is maternal
• Homozygous: When genes are identical
• Heterozygous: When genes are different

Elements of Formal Genetics: Genotype vs Phenotype

What is the difference?

Genotype "genes"

• Actual genetic information carried by the individual
• All cells except the gametes of an individual have the same genotype.
• Not all genes are expressed in all cells.

Phenotype "physical"

• Expression of genes
• Appearance of the individual’s characteristics "outward appearance"

EX:

• infant who is born with an inability to metabolize the amino acid phenylalanine has the single-gene disorder known as phenylketonuria (PKU) and thus has the PKU genotype
  • If the condition is left untreated, abnormal metabolites of phenylalanine will begin to accumulate in the infant's brain and
    irreversible intellectual disability
  • ~Foods high in phenylalanine include proteins found in milk,
    dairy products, meat, fish, chicken, eggs, beans, and nuts~
• Intellectual disability is thus one aspect of the PKU
  phenotype

Elements of Formal Genetics: Dominant vs Recessive

• The allele whose effects are observable is said to be dominant= capital letter
• The allele whose effects are hidden is said to be recessive= lower case letter
• When one allele is dominant over another, the heterozygote genotype Aa has the same phenotype as the dominant homozygote AA. For the recessive allele to be expressed, it must exist in the homozygote form, aa.
• Alleles are either heterozygote or homozygote
• Alleles can be codominant; that is, both alleles are expressed.
• Carrier
  • Has a disease allele but is phenotypically normal, Can pass disease to offspring

What are 4 major types of genetic disease ?

single-gene diseases can be classified into four major modes of inheritance

1.Autosomal dominant

2.Autosomal recessive

3.X-linked dominant

4.X-linked recessive

Autosomal Dominant

Who is most likely to pass the gene, Male? Female? Equal?

Probability of offspring

Example

• Condition is expressed equally in males and females.
• Males and females are equally likely to pass the gene to his or her offspring.
• On average, half the children will be heterozygous and will express the disease, and half will be normal.
• No generational skipping occurs.
• The probability that an individual will develop a genetic
  disease is termed the recurrence risk.
• EX: Huntington disease, a neurologic disorder whose
  main features are progressive dementia and increasingly uncontrollable limb movements
  • Onset is age 40
• Examples include:
• Adult polycystic kidney disease
• Huntington’s chorea
• Familial hypercholesterolemia
• Marfan’s syndrome

Autosomal Recessive Inheritance

Who is most likely to pass the gene, Male? Female? Equal?

Probability of offspring

Example

• Condition is expressed equally in males and females.
• Abnormal allele is recessive
• Homozygous recessive child has the disorder.
• Heterozygous child No clinical signs of disease, Child is a carrier
• Consanguinity (marriage between related individuals) is sometimes present, especially in cases of rare recessive diseases.
• recurrence risk for the offspring of carrier parents is 25%.

Examples include:

• Cystic fibrosis
• Sickle cell anemia
• Phenylketonuria

Cystic fibrosis, the most common lethal recessive disease in white children

gene responsible for cystic fibrosis encodes a chloride ion channel in some epithelial cells.

Defective transport of chloride ions leads to a salt imbalance, which
results in secretions of abnormally thick, dehydrated mucus. Some digestive organs, particularly the pancreas, become obstructed, causing malnutrition, and the lungs become clogged with mucus, making them highly susceptible to bacterial infections

X-linked Dominant Disorders

Some genetic conditions are caused by mutations in genes located on the sex chromosomes, and this mode of inheritance is termed sex linked

• Heterozygous males and females affected
• Reduced penetrance in females
• males more commonly affected

Example:

• Fragile X syndrome
  

Most common genetic cause of cognitive deficits.

.X-Linked Recessive

• Occurs significantly more often in males than in females.
• Males only need 1 copy of the recessive allele (from mom) to express the disease.
• Females need 2 copies of the recessive allele (one from each parent) to express the disease.
• Heterozygous females are carriers.
• Inheritance may appear to skip generations.

Examples include:

• Hemophilia A
• Color blindness
• Duchenne muscular dystrophy: characterized by progressive
  muscle degeneration. Affected individuals usually are unable to walk by age 10 or 12 years. The disease affects the heart and respiratory muscles, and death caused by respiratory or cardiac failure usually occurs before age 20 years