Human Genetics

1. Human Genetics Chapter 14

2. Quick Chromosome Review • What are chromosomes made of? • DNA & PROTEINS • When are chromosomes visible? • CELL DIVISION • What does it mean to be diploid? • Have two sets of chromosomes • One from mom & one from dad! • Which cells are not diploid? Why? • Gametes: haploid sperm (23) haploid egg (23) • They must combine to form a diploid zygote (46)!

3. Sex Chromosomes • Determine an individual’s gender • Two chromosomes within the genome • XX – Female • All human eggs carry an X chromosome (23, X) • X chromosome has > 1200 genes • XY – Male • About half of sperm cells carry an X, the other half carry a Y (23, X or 23, Y) • Y chromosome is much smaller and has only about 140 genes • mostly associated with male sex determination and sperm development

4. Autosomal Chromosomes • Remaining 44 human chromosomes • Humans have 46 total chromosomes • 44 autosomal chromosomes (22 pairs) • 2 sex chromosomes • To correctly label a karyotype or summarize the number of chromosomes in a human cell: • 46, XX (females); 46, XY (males)

5. Human Pedigrees • Chart that shows relationships within a family • Shows presence or absence of a trait and how it is passed on through a family • used for any species • used to infer genotypes of family members • can determine if allele is dominant, recessive, autosomal, or sex-linked • used to determine who in a family is at risk for genetic conditions by genetic researchers or counselors

6. Human Pedigree Children are placed from oldest  youngest Key explains what trait is!

7. ff ff Ff ff Ff Ff • Steps: • Identify all people who have the trait. • For the purpose of this class all traits will be given to you. In other instances, you would have to determine whether or not the trait is autosomal dominant, autosomal recessive, or sex-linked. • In this example, all those who have the trait are homozygous recessive. • Can you correctly identify all genotypes of this family? • F- Normal • f- cystic fibrosis Key: affected male affected female unaffected male unaffected female

8. PKU P- Unaffected p- phenylketonuria Key: affected male affected female unaffected male unaffected female Pp Pp Pp pp PP or Pp pp pp Pp Pp

9. H-huntington’s disease h-Unaffected Key: affected male affected female unaffected male unaffected female hh Hh hh Hh hh Hh hh Hh hh

10. Sex-Linked Inheritance Colorblindness Key: affected male affected female unaffected male unaffected female XCY XcXc XcY XCXc XcY XCXc XcY

11. Karyotypes • To look at the human genome, biologists photograph human chromosomes during mitosis (usually metaphase) • Cut them out and arrange them into a picture called a karyotype • Shows the complete diploid set of chromosomes grouped together in pairs • Arranged in order of decreasing size

12. Normal Human Male (46, XY)

13. Normal Human Female (46, XX)

14. X Chromosome Inactivation • Females have an extra X chromosome • Most of genes in one of X chromosomes turned off • Forms dense region in nucleus called a Barr body • Same process in other mammals • i.e. calico cats

15. Human Genetic Disorders • Review: what is a mutation? • Change in DNA sequence • Changes proteins by altering amino acid sequence! • Can directly affect the phenotype expressed! • Many genetic disorders are caused by changes in an individual gene!

16. Sickle Cell Disease • Caused by a defective allele for a protein in hemoglobin • Causes hemoglobin molecules to stick together and form sickle shape • More rigid and get stuck in capillaries • Results in loss of blood flow and damage to cells, tissues, and organs

17. Cystic Fibrosis • Known as CF • Results from deletion of just three bases in gene for a protein called CFTR • Protein is destroyed and doesn’t work as a transport protein, so proper ions aren’t transported across cell membrane • Recessive trait – need two copies of defective allele for CF • Serious digestive problems and thick, heavy mucus clogs lungs and breathing passageways

18. Huntington’s Disease • Caused by dominant allele for a protein found in brain cells • Mental deterioration, uncontrollable movements, appears in middle age Dominant, Autosomal

19. Genetic Advantages • How do fatal alleles remain in the gene pool? • Heterozygous individuals often show genetic advantages in certain situations • Those heterozygous for sickle-cell are highly resistant to malaria • Those heterozygous for CF had an advantage in medieval times and were resistant to Typhoid Fever

20. Chromosomal Disorders • Errors can occur in meiosis • Homologous chromosomes can fail to separate during Anaphase I • Nondisjunction • Results in gametes with an abnormal number of chromosomes • Trisomy = 3 copies of a chromosome • Down syndrome = Trisomy 21 • Mild to severe mental retardation • High frequency of birth defects

21. Male: 47, XY, +21Female: 47, XX, +21 Trisomy 21

22. Klinefelter’s Syndrome, 47 XXY Sex Chromosome Disorders • Turner’s Syndrome • Nondisjunction of X chromosome • Female inherits only one X chromosome • Results in sterility and reproductive organs do not develop properly • Klinefelter’s syndrome • Males inherit extra X chromosome • Interferes with meiosis and usually causes sterility • No cases of babies born without X! • Necessary for survival of embryo XXY

23. Human Genome Project • Launched in 1990 • Main goal: sequence 3 billion base pairs of human DNA and identify all human genes • Completed in 2003 • Completed genomes of many other organisms while working through human genome • 40% of our proteins have strong similarity to proteins in many of those organisms (fruit fly, worms, yeast)

24. Human Genome Project • Only about 2% of genome encodes instructions for synthesis of proteins • Large areas of chromosomes with very few genes • Pinpointed genes and associated particular sequences in those genes with diseases and disorders • Identified about three million locations where single-base DNA differences occur in humans • Help us find sequences associated with diabetes, cancer, and other health problems

25. HGP: What now? • Ethical, legal, social issues • Who owns and controls genetic information? • How does genetic privacy relate to medical privacy? • May 2008: Genetic Information Nondiscrimination Act • Prohibits US insurance companies and employers from discriminating on basis of information derived from genetic tests • Still don’t understand as many as 50% of the human genes thus far discovered