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