1) Gene mutations and chromosomal abnormalities can cause a variety of genetic disorders and diseases. 2) A single base pair change in DNA can cause mutations like sickle cell anemia, while errors in meiosis can result in aneuploidies including extra or missing chromosomes. 3) Examples of genetic disorders include Tay-Sachs disease, cystic fibrosis, Huntington's disease, and Down syndrome which is caused by trisomy 21. These disorders alter genes and result in physical or mental impairments.

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 .

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 ?.

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 )