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