Human Genetics

• Man is considered to be an awkward subject for genetic investigation
• Reasons man is an awkward subject for genetic investigation

  • Long life cycle
  • Low number of progeny
  • No desire to be exposed to rigorous experimental conditions
• Analysis of inheritance of traits

  Pedigree analysis or family history
• Common Pattern of Inheritance:

  Autosomal Dominance


  Due to a dominant allele, never skips a generation, e.g. free earlobes
• Common Pattern of Inheritance:

  Autosomal Recessive


  both sexes affected equally, skips a generation, ex. inability to roll tongue
• Sex-linked Dominance


  Affected husband with unaffected wife will have an affected daughter, e.g. defective enamel of the teeth
• Sex-linked Dominance Genotypes


  • Female: affected - XEXE, XEXe, unaffected - XeXe
  • Male: affected - XEY, unaffected - XeY
• Sex-linked Recessive


  Affected wife with unaffected husband will have an affected son, e.g. colorblindness
• Sex-linked Recessive Inheritance


  Male: affected - XhY normal - XHY

  Female: affected - XhXh normal - XHXH, XHXh
• Sex-influenced


  Trait has greater expressivity in one sex, e.g. pattern baldness
• Sex-influenced Baldness Genotypes


  • Female: Bald - BB Non-bald - Bb, bb
  • Male: Bald - BB, Bb, Non-bald - bb
• Chromosomal Aberrations


  • Autosomal: Down's Syndrome, D trisomy Syndrome, E trisomy
  • Sexual Anomalies: Klinefelter's Syndrome, Double Y or Jacob's Syndrome, Turner's Syndrome, Triplo X Syndrome, Hermaphroditism
  • Structural Changes: Cri-du-chat syndrome, Philadelphia chromosome
• Down's Syndrome


  22 IIA + I21 or 22, XX, XY, slanting narrow eyes, saddle nose, large ridged tongue, flattened face, happy, affectionate disposition, low IQ (25-74)
• Chromosome 21


  • Smallest of the human chromosomes, chromosomal imbalance is less severe hence individual survives, oocyte of female arrested at prophase I, one secondary oocyte is released per ovulation, finish meiosis I and II if fertilized, the longer the time the oocyte is arrested there could be non-disjunction
• Down's Syndrome

  Non-disjunction at anaphase I or anaphase II
• D trisomy Syndrome


  22 IIA + I13, 14, 15, 1 in 10,000 births, life expectancy 0 – 1000 days; ave. 131 days, anomalies in the eyes, brain, heart
• E trisomy


  22 IIA + I 16,17, 18, ave. 239 days
• Edward's Syndrome - trisomy 18


  80% are female, multiple congenital malformations in all organs, clenched fists, elongated skull, low set ears
• Klinefelter's Syndrome


  22 IIA + XXY, under developed males, small testis, no spermatogenesis, sterile, no body hair, enlarged breast, high pitched voice, socially inadequate, dependent, submissive, rambling talkativeness
• Double Y or Jacob's Syndrome


  22 IIA + XYY, anti-social, aggressive, with criminal tendencies, unusual sex taste including homosexuality, exceptionally tall, acne scarred face, epileptic
• Turner's Syndrome


  22 IIA + XO, webbed neck, sexually infantile, short stature
• Triplo X Syndrome


  22 IIA + XXX, menstrual irregularities, premature menopause, secondary amenorrhea, sub normal mental abilities
• Hermaphroditism


  22 IIA + X y, with testicular and ovarian tissues, with congenital anomalies
• Muscular Dystrophy


  Duchenne or Becker, deletion in X (frameshift), gene for dystrophin, progressive deterioration of muscles
• Cri-du-chat syndrome


  French for "cat cry", terminal deletion in the short arm of chromosome 5, small head, multiple organ deformities
• Philadelphia chromosome


  t (22q; 9q), chronic myelogenous leukemia
• Republic Act No. 9288 (Newborn Screening Act of 2004)
• Newborn Screening


  Find out if the baby has hidden rare disorders, done 24 hr after birth or on the 3rd day, can detect inborn errors of metabolism, Expanded Newborn Screening
• Congenital hypothyroidism (CH)


  Absence of thyroid hormones, essential to growth of brain and body, may suffer mental retardation, hormone treatment
• Congenital adrenal hyperplasia (CAH)


  Severe salt loss, dehydration, abnormally high levels of male sex hormones in both boys and girls
• Galactosemia


  Can't synthesize gal-1 p uridyl transferase, can't utilize galactose as a source of energy, liver and brain damage
• Phenylketonuria


  Can't synthesize phenylalanine hydroxylase, brain damage, mental retardation, albinism
• Glucose 6 phosphatase dehydrogenase deficiency (G6PD)


  Leads to anemia, yellow discoloration of the skin, other health problems if exposed to certain drugs, food and chemicals
• Other Genetic Disorders


  • Sickle cell anemia
  • Thalassemia
  • Congenital cataract
• Sickle cell anemia


  Substitution of valine for glutamic acid, hemoglobin S
• Thalassemia


  Persistence of fetal hemoglobin, homozygote will have hypochromic anemia, marrow hyperplasia, heterozygote - mild hypochromic microcyte anemia
• Congenital cataract


  Mutation in the crystallin gene protein in the lens of the eyes, improper folding of protein
• Schizophrenia


  Loss of the ability to organize thoughts and perception, psychosis includes delusions and hallucinations, display inappropriate emotional responses, 10% commit suicide, 17-27 years old (male), 20-37 years old (female), 80 % concordance in identical twins, 54 % concordance in fraternal twins, susceptibility genes on chromosomes 1, 4, 6, 9, and 11
• Environmental Risk Factors for Schizophrenia

  • Maternal malnutrition
  • Borna virus infection
  • Fetal oxygen deprivation
  • Birth complications
  • Psychoactive drug use
  • Traumatic brain injury
  • Herpes infection at birth
• Anorexia nervosa


  Psychological disorder, perceives oneself as obese, starves intentionally, death risk, 15-21%