Human Genetics Ch. 13.1-13.4

1. Human GeneticsCh. 13.1-13.4

2. Why Study Our DNA? • Learn the effects of mutations • Understand how genetic diseases are generated • Propose possible treatments for genetic diseases • Identify causes of genetic diseases • Unfortunately, inheritance is mostly NON-Mendelian • The alleles for traits are passed on and expressed in complex ways

3. Genetic Linkages • What is Mendel’s Principle of Independent Assortment? • Genes are separated independently into gametes and thus offspring • We have only 23 chromosomes, why is complete independent assortment impossible? • 100,000 of genes and only 23 chromosomes to be condensed into; some genes have to share the same chromosome • Genes on the same chromosome are linked genes • In order to study inheritance of multiple genes, we are going to have to map out what genes are on what chromosomes

4. Mapping A Chromosome • Morgan and Sturtevant; 1900’s • Cross-breeding fruit flies; Drosophilamelanogaster (model genetic studies organism) • pr+pr+vg+vg+ red eyes; long wings • “+” = wild type (normal/dominate) • prprvgvg purple eyes; vestigial wings • Expected 1:1:1:1 ratio (all combinations of eye color and wing type) • Got almost 1:1 of parental phenotypes (Red/Long: Purple/Vestigial • Small percent were Red/Vestigial or Purple/Long (recombinant phenotype)

5. Mapping A Chromosome • Why a near 1:1 of the parental phenotypes? • Genes are linked; eye color and wing type are on the same chromosome • Why the small percent of recombinant phenotype? • Crossing Over during meiosis; Genes must have been switched on homologous chromatids • If two sections of a chromosome are switching places, than what can you conclude about the percent of genes you would see switched in an organism? • The further away the genes are from each other on the chromosome the more likely they will get switched

6. Recombinant Frequencies • Of the F1 generation; 305 had recombinant phenotypes of the 2,839 total progeny (offspring). What is the recombinant frequency? • 10.7% (305/2,839 *100) • Sturtevant brilliantly deduced that recombinant frequencies between multiple linked genes could be use to map out the locations of genes on their chromosome • <1% - 50%; Why is 50% the max? • Progeny get either parental chromosomes or recombinant chromosomes (50%) • Linkage map

7. Linkage Map • Written in mu (map units) or cM (centimorgan); map shows relative location based on other known alleles • Map of alleles a, b, and c: • a-b 9.6% = 9.6 mu • b-c 2% = 2 mu • a-c 8% = 8 mu • a must be far from b and c must be between them, but much closer to b • 9.6 mu (a-b)– 2 mu (c-b)= 7.6 mu(a-c) • Why the inconsistency? • a is pretty far from c and b so there may be a double cross over sometimes • What can we conclude about genes more the 50 mu apart? • They follow independent assortment (no linkage) because 50% is highest possible recombinant frequency

8. The Amazing Drosophila • Genes linked to sex chromosomes also discovered through fruit flies • Doing a F2 cross Morgan expect the normal 3:1 but instead he got all females with red eyes and 50% males with white or red eyes • What does this tell us? • Eye color is sex linked; X chromosome • Males have a 50% of getting Xw+ or Xw; females all get at least one Xw+ so they all have red eyes • X-linked recessive all males progeny of a XrXr x YXRget Xr

9. Sex-Linked Genes • Any genes located on the sex determining chromosomes • X or Y in humans • Mapped through male/female dependent inheritance • All other 22 chromosomes are called autosomes (automatically inherited) • Y Chromosome • Sex-determining genes; SRY gene makes females into males while an embryo • Maybe fading from existence; may be getting smaller • XY heterogametic • X Chromosome • Mostly codes for non-sex related traits (ex. Color vision) • XX homogametic

10. Too Many Xs! • Why do females need two Xs? • They Don’t! Two X chromosomes would mean double the genetic material necessary • What does the body do with the X chromosome? • It randomly shuts one X down • Creates a Barr body dense mass of inactive chromatin • They are copied and passed on in mitosis but are never used for proteins • How can this show us X-recessive traits? • Dominate X might be randomly deactivated so the X recessive is randomly present in cells • Female calico cats have a mix of orange and black fur but males are always black or orange

11. Following Sex-linked Traits • Pedigree map of parents and offspring in a family over generations • ⃝ female •  males •  has trait •  carrier; has gene but not trait • Hemophilia platelets numbers so low person often bleeds to death from little body damage • X-linked recessive gene • Rare for XhXh why? • Most males with the disease do not reproduce • Lead to the Russian Revolution

12. Chromosomal Mutations • Major change in a chromosome's structure or the number of chromosomes in a gamete • 4 Types: • Deletion • Duplication • Translocation • Inversion

13. Deletions and Duplications • Deletion section of chromosome is lost • Cri-du-chat (cat’s cry) • Deletion from Chromosome 5 causes mental retardation and malformed larynx • Cry sounds like cat meow • Duplication section is inserted to a homolog that already has that section • Why can two copies allow the slow testing of mutations? • One mutated copy tests adaptation but organism basically functions normally • Hemoglobin in humans has evolved this way

14. Translocation and Inversion • Translocation section attached to non-homolog • Typically reciprocal (two chromosomes each have translocation) • Philadelphia Chromosome translocation of 9 and 12; causes uncontrolled growth in white blood cells (leukemia) • Inversion section attached to original chromosome but in the reverse order • Genes lose function or produce harmful/beneficial new versions

15. Non-Disjunction • Euploidy normal amount of chromosomes • Aneuploidy missing or extra amount of chromosomes • Monoploids, triploids, tetraploids, ….polyploids • Most miscarriages (baby deaths before birth) are aneuploidy • Trisomy 21 and 18 develop but live short and difficult lives • X and Y polyploidy survive… • XYY? • Extra Y’s just mean more male characteristics; no essential genes • XXY and XXX? • Barr bodies turn off extra Xs

16. Human Inheritance Patterns • Autosomal Recessive • RR no trait • Rr carriers • rr show the trait • CF Cystic Fibrosis • 1:4,000 births in US • Lose Cl- channel transport efficiency • Build up of thick mucus blocks lungs and promotes disease • PKU Phenylketonuria • 1:15,000 births in US • Enzyme cannot break phenylalanine into tyrosine • Build up causes brain damage • Must be medicated and restrict diet

17. Human Inheritance Patterns • Autosomal Dominate • RR have trait • Rr have trait • rr no trait • Dwarfism Achondroplasia • 1:25,000 births worldwide • Only heterozygous survive embryo development • Defective cartilage leads to short arms and legs; large heads; regular sized body

18. Human Inheritance Patterns • X-Linked Recessive • XX no trait • XXr carries • XrXr have trait • DMD Duchenne muscular dystrophy • Muscle tissue degrades; most cannot walk or need crutches • Dystrophin is defective; protein anchor in muscle cells; results in tearing • X-Linked Dominate • XX have trait • XX have trait • XrXr no trait • Extremely rare in humans • Teeth discoloration

19. Genetic Disease Testing • YOUR TURN! • Write a 2 page essay (12 size arial font, normal margins) on 3 methods used today to test for genetic diseases • Two may come from your book • One MUST come from an outside source • You essay should have details in how the process works and the pro and cons (good and bad parts) • Essay is due 12/13, in print

20. Homework • Actual: • Essay on Genetic Screening • Fruit Fly Lab • Apply Evolutionary Thinking (p.280) • Suggested: • Test Your Knowledge (Ch. 13) • Design the Experiment (Ch. 13) • Test on Ch. 11, 12, and 13 on Thursday