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  • 1. Gene defect/ chromosome mutations
  • 2. Essential terms
    • Mutation
    • Variation
    • Aneuploidy
    • Euploidy
    • Poluploidy
    • Monosomy
    • Trisomy
    • Non disjunction
    • Sex linked
    • Autosomal D/R
    • Monogenic
    • Polygenic
  • 3.
    • Any form of modification =
    • chromosomal mutation/aberration .
  • 4.  
  • 5.
    • A Change in a Single DNA Base Can Cause a Mutation
  • 6. Eg. Sickle cell anaemia
      • A mutation caused a GAG codon to change into a GUG codon in the gene for one of the protein chains of hemoglobin
      • mutation replaced the glutamic acid a2 with valine
      • Conseqences = hemoglobin stick together and causes damage to RBC = anemia
      • The mutation also gives some resistance to malaria in individuals with one sickle gene and one normal gene
  • 7. Inborn errors of metabolism
    • Most mutations are harmful
    • Caused by chemical and physical agents which damage DNA (UV light, x-rays, many carcinogenic & mutagenic chemicals)
    • Approx. 600 genetic diseases known
    • Gene therapy = correcting defective gene
  • 8. Autosomal recessive
    • PKU = lacks the ability to synthesize an enzyme to convert the amino acid phenylalanine into tyrosine
    • Built up phenylalanine and abnormal breakdown products in the urine and blood.
    • Affects the CNS = mental impairment.
    • 1 in 15,000 infants suffers from this problem.
    • PKU sufferers are placed on a diet low in phenylalanine sufficient for metabolic needs
  • 9. Autosomal recessive
    • Tay-Sachs Disease = degeneration of the nervous system.
    • Lack the ability to make the enzyme N-acetyl-hexosaminidase, which breaks down the ganglioside lipid. This lipid accumulates in lysosomes, casuing death to brain cells.
    • Symptoms manifest after birth.
    • Rarely survive past five years of age.
    • 1 in 300,000 births) in general pop, but 1 in 3600 births among Jews
    • One in 28 American Jews is thought to be a carrier
  • 10. Autosomal recessive
    • Albenism = the lack of pigmentation in skin, hair, and eyes
    • 1) the lack of enzyme along the melanin-producing pathway;
    • or 2) the inability of the enzyme to enter the pigment cells and convert the amino acid tyrosine into melanin.
  • 11. Autosomal dominant
    • Huntington’s disease - progressive destruction of brain cells.
    • The disease usually does not manifest until after age 20-30.
    • Polydactly is the presence of a sixth digit common with this trait.
  • 12. Sex linked
    • Red-green colorblindness. 8% M, 0.04% F. X.
    • Hemophilia- defective blood clotting protein
    • Muscular dystrophy- DMD. 1 in 35,000. Muscle wasting disease.
  • 13. Variation in number
    • Random error during the prod. of gametes.
    • Non disjunction= disruption of the normal distribution of chr to gametes.
    • Consequent of this failure of separation = variety of autosomal aneploid conds. Eg 47XXY, 45X
  • 14. Sex determination
    • XX , XY
    • Hormones affect phenotypic expression
    • All individuals have genes to develop into either sex. Depends on sex chromosome and meiosis.
    • Meiosis = creates genetic variability and ensures genetic consistency. Depends on fertilization.
  • 15. Y chromosome
    • Fewer genes.
    • PAR (pseudoautosomal regions)
    • MSY (male specific region of Y)
    • SRY (sex determining region of Y) sex determination
    • SRY encodes a gene product that triggers the gonadal tissue to form testes. Product = TDF
    • SRY present = testes and testosterone forms
    • SRY absent= gonads develop as ovaries
  • 16. Susceptible genes
    • contribute risk, but don’t cause it.
    • influence the age of onset, rate of progression, or help to protect against it
    • Different alleles may be associated with different degrees of susceptibility, or risk.
    • The APOE gene on chromosome 19
    • An individual who has two copies of one variant allele of APOE is more likely to develop Alzheimer disease at an earlier age than an individual with a different APOE genotype.
  • 17. Variation in chromosome number
    • Aneuploidy = gain or loss one or more chr.
    • Monosomy = 2n – 1. eg. 45X
    • Trisomy = 2n + 1.
    • Euploidy = complete haploid set of chr (x)
    • Polypliody = more than 2 sets of chr.
    • Triploid = 3 sets
    • Tetraploid = 4 sets.
  • 18. Klinefelter syndrome
    • Aneuploidy = Extra X chromosome (XXY).
    • 2 in 1000 male births. Lower incidence that 47XXY
    • Sex ? Intersexuality
    • Male genitalia and internal ducts but testes rudimentary and X produce sperm.
    • Tall, long arms/legs, large hands/ feet.
    • Gynecomastia and rounded hips.
    • Intelligence below normal range.
    • Y chromosome determines maleness.
  • 19. Other abnormal karyotypes
    • 48 XXXY
    • 48 XXYY
    • 49XXXXY
    • 49XXXYY
    • All are similar phenotypically to 47XXY.
    • The greater number of X chromomes, the greater the manifestations.
  • 20. XXX karyotype
    • 47XXX. 1 in 1200 female.
    • Extra X chr appears to disrupt the balance of gen info needed for female developmt.
    • Some may be normal, others may have underdeveloped sex chrtc, sterility and mental impairment.
    • 48XXXX
    • 49XXXXX.
  • 21. 47 XYY karyotype
    • Additional Y chromosome.
    • Tall – over 6 feet.
    • In the past -Incarcerated – predispositon to criminal acts, personality disorders and subnormal intelligence.
    • High numbers in mental institutions.
    • Now –studies shows there is little consistent correlation between extra Y chromosome and behaioral problem.
  • 22. Monosomy
    • Turner syndrome 45X.
    • 1 in 2000 female births.
    • Female genitalia and internal ducts, ovaries rudimentary.
    • Short stature, broad chest, skin flaps back of the neck, underdeveloped breasts.
    • Sex ?.
  • 23.  
  • 24. Partial monosomy
    • Segmental deletions cri-du-chat syndrome.
    • 1 in 50,000 births
    • Loss of small part of chr 5 = 46-5p.
    • Anatomical malformations – GI and cardiac complications, often mentally challenged.
    • Abnormal glottis and larynx develop. = infant cry
    • Longer the deletion = greater the impact of physical, psychomoter and mental skills.
  • 25. Trisomy
    • 1866 J. Landon Down = Down syndrome
    • Trisomy 21 (47 +21). ND of chr 21.
    • 1 in 800 live births.
    • Extra chromosome maternal? > in ageing mum.
    • 12- 14 cht. Physical, psychomoter and mental develop. Impairment.
    • Mongoloid appearance = flat face, round head, short, short, broad hands
    • Short life span
    • Prone to RTI, heart malformations, > leukemia, alzheimer
    • Early diagnosis – Amniocentesis and CVS.
  • 26. Other trisomy
    • Patau syndrome = Trisomy 13
    • 1 in 19,000 births.
    • Mentally challenged, partially deaf, clrft palate, congenital malformation of most organ system.
    • Average survival rate = 3 mths.
    • Edwards syndrome = Trisomy 18
    • Infants smaller than average newborn.
    • Congenital malf, death within 4 mths. (Pneumo )