Genes & Genetic Mutations

Genetics Basics

23 pairs of chromosomes, 46 total

22 are autosomes, and 1 pair is the sex chromosomes

• Aneuploidy: the presence of, or absence of one or more chromosomes
    * Trisomy: three copies of one chromosome
    * Monosomy: only one copy of any chromosome, is often lethal

%%★ It is better to have extra than less ★%%

• Nondisjunction: cause aneuploidy; failure of homologous chromosomes to separate normally during mitosis/meiosis

Autosomal Aneuploidy

• ==Cause of aneuploidy = nondisjunction ==
• Do not involve the sex chromosomes
• Abnormal amount of chromosomes (ex: 45 or 47)
• Ex: Down syndrome (trisomy 21)

Sex Chromosome Aneuploidy

• Involves the sex chromosomes
• Abnormal amount of X chromosomes
    * Ex: Turner (X) or Klinefelter (XXY or XXXY)

Autosomal Dominant

• ==Does NOT skip generations==
• ==NO CARRIERS==
    * Affected offspring produced by normal parent and affected heterozygous parent
    * Half of offspring normal; half will express disease
• Only affects structural changes
• Usually develops later in life, usually people afflicted have already had children
    * Ex: Huntington, neurofibromatosis, marfan’s

Autosomal Recessive

• ^^Skips generations; has CARRIERS ^^
• Most cases, both parents of affected individuals are heterozygous carriers
    * Recurrence risk for offspring is 25%
      * 50% carriers
      * 25% normal
    * Males and females equally affected
• Ex: Cystic fibrosis, sickle cell anemia, PKU, Tay-Sachs
• Most don’t live past the age of 20yrs

Sex-Linked Inheritance

• Most X-Linked disorders are recessive
• Mother → Son
    * 50% risk of being affected
• Father → All of his daughters affected
    * Ex: Hemophilia

==Down Syndrome==

• AUTOSOMAL ANEUPLOIDY
• Trisomy 21
• Caused by nondisjunction
• More commonly caused by increased maternal age ( >35yrs)
• Presents:
    * Flat facial profile
    * Congenital heart disease
    * Growth failure
    * Range of mental retardation

$Turner Syndrome (45 X)$

• SEX CHROMOSOME ANEUPLOIDY
• Affects females only
• One X chromosome
• Characteristics:
    * Short stature
    * No menstrual cycles
    * High number of aborted fetuses
    * Usually inherited from mother

$Klinefelter Syndrome (47 XXY)$

• SEX CHROMOSOME ANEUPLOIDY
• Affects males only
• At least 2 Xs and 1 Y
• Characteristics:
    * Tall stature
    * Gynecomastia
    * Wide hips
    * Long arms & legs
    * Have Barr bodies

^^Huntington Disease^^

• AUTOSOMAL DOMINANT
• Chromosome 4
• Characteristics:
    * Chorea
    * Doesn’t skip generations
    * Severe degeneration of the basal ganglia and cerebral cortex; depletion of GABA
    * 5 year time frame of survival

^^Neurofibromatosis^^

• AUTOSOMAL DOMINANT
• aka von Recklinghausen disease
• Characteristics:
    * Cafe au lait spots
    * Neurofibromas
    * Located on chromosome 17

%%Cystic Fibrosis%%

• AUTOSOMAL RECESSIVE
• Most common in Caucasians
• Impacts the lungs and digestive system
• Defective CFTR gene
    * Lifespan ~20-25yrs

%%Sickle Cell%%

• AUTOSOMAL RECESSIVE
• Most common in African Americans
• Deoxygenation and dehydration causes a sickle shape in RBCs

@@Hemophilia@@

• SEX/X-LINKED RECESSIVE
• Serious bleeding disorders
• Involve gene deletions or point mutations
• First signs by 3-4 yrs
    * Hemophilia A (VIII deficiency)
    * Hemophilia B (IX deficiency)
    * Hemophilia C (XI deficiency)

Punnett Square for X-Linked Recessive

Normal father, carrier mother; most common route