Genetics

1. Genetics

2. Genetics Molecular Genetics:study of the structure and function of chromosomes and genes Heredity:transmission of characteristics from parents to offspring Trait:two contrasting choices Genotype:genetic makeup of organism (TT, Tt, tt) Phenotype:what is physically observed (tall, short) Heterozygous:two different alleles (Tt); hybrid Homozygous:two identical alleles (TT, tt); purebred

3. Gregor Mendel • Austrian Monk, born in 1822 • University of Vienna • Job at monastery was to teach science and tend the garden • Major study done on characteristics of pea plants

4. Pollination • Pollination:pollen grains from male part of plant fertilize the egg from the female portion of the plant • Self-Pollination:pollen and egg from same plant; all offspring characteristics the same as parent (Pea Plants) • Cross- Pollination:pollen and eggs from different plants; offspring characteristics formed from a combination of parental genes

5. Parts of the Flower • Male: • Stamen:anther + filament • Anther:produces pollen grains • Filament:holds up anther • Female: • Stigma:top of pistil, sticky to catch pollen • Style:tube leading from stigma to ovary • Ovary:contains ovules • Ovules:when fertilized will become seeds

6. Pea Plants • Closed petals • Always self-pollination • Purebred:if allowed to self-pollinate, all offspring identical to parents • EX:all short, tall • Experiment:Mendel prevented self-pollination by removing stamen and using a paint brush to transfer pollen grains to stigma • Results • Hybrids:produced by crossing parents with different characteristics

7. Experiment • Dominant Traits:characteristic that when present is always expressed • Recessive Traits:masked by dominant trait; only appears if there are two copies • P-Generation:purebred parent generation; produce offspring identical to themselves • Ex:Mendel found: tall/tall produced only tall, short/short only short • F1- Generation:first filial generation; produced by cross-pollination • Ex:Mendel found tall/short produced tall plants • F2- Generation:second filial generation; offspring of crossed F1 • Ex:tallF1/tallF1 = tall and short plants

8. Parent Generation TT or tt F1 Generation TT x tt Punnett Squares • A diagram to aid in predicting the probability that certain traits will be inherited. • Monohybrid Cross:Punnett square involving only one trait (2x2) F2 Generation:Tt x Tt T T T t Genotypic Ratio: 1:2:1 Genotypic Ratio: 4:0 Tt t t T t Phenotypic Ratio: 3:1 Phenotypic Ratio: 4:0 tall

9. Mendel's Conclusions • Gene:individual factors that do not blend with one another; control traits in living things • Allele:each alternative for a gene; genes/chromsomes occur in pairs; Ex: T and t • Law of Segregation:Alleles are segregated (separated) during meiosis. Only one allele from parent is present in gamete. Occurs during anaphase when chromatids separate. • Law of Independent Assortment:factors for different traits are separated during meiosis; dominant traits are not necessarily inherited together

10. Testcross • How can you tell if a phenotypically dominant organism is homozygous or heterozygous? • Cross with a recessive • If homozygous: offspring will all be dominant. • If heterozygous: offspring will be both dominant and recessive.

11. Gene Interactions

12. Gene Interactions • Complete Dominance:when one allele totally masks the other allele • Dominant trait occurs with TT or Tt, recessive only tt • Ex:Tall plants, rolling tongue upwards, crossing hands • Ratio when crossing two heterozygous: 3:1

13. Gene Interactions • Incomplete Dominance:occurs when two or more alleles influence the phenotype; when heterozygous, results in a third BLENDED phenotype • Ex:Red and white flowers = pink • Ratio: 1:2:1

14. Gene Interactions • Codominance:occurs when both alleles for a gene are expressed in a herterozygous offspring; DO NOT BLEND, both are equally dominant • Ex: Roan Horse • Ratio: 1:2:1

15. Sickle Cell Anemia • Recessive • Defective Hemoglobin on RBCs • Anemia (loss of blood cells) • Damage to brain, heart, lungs • Primarily in African Americans; 1/10 in US is a carrier

16. Cystic Fibrosis • Recessive • Point mutation stops production of a protein in the lungs and pancreas • Prevents cells from transporting Cl- ions out of the cell • Lung Congestion • Abnormally thick mucus lining in lungs • Chronic Bacterial Infections (pneumonia) • Treated with antibiotics, lung transplant, and new genetic engineering treatments

17. Tay Sachs • Recessive • Lack of enzyme hexosaminidase A (hex A), which breaks down fatty acids in brain in nervous tissue • Symptoms appear at 4-6 months • Death by 5 years • Found primarily in those descendants of Ashkenazi Jews • 1/30 American Jews carry the gene

18. Huntington's Disorder • Autosomal- Dominant • Lethal • Begins around ages 35-45 • First symptoms; mild forgetfulness and irritability • Lose control over muscles • Genetic Marker: short section of DNA that has a close association with a known gene • Presence of gene marker can indicate the presence of huntington’s allele • People with marker have 90% chance of developing Huntington’s • Gene Marker and gene so close on chromosome rarely separated by crossing over during meiosis

19. Marfan's Syndrome • Dominant Disorder • 1/20,000 people • Believed to be caused by a mutation in the fibrillin gene on chromosome 15 • Connective Tissue defects • Dislocation of lens in eye • Rupture of aorta (weak vessel walls) • Arachnodactyly – “spider fingers” • Elongated body, face • Pectus Excavatum (caved in chest)

20. Marfan's Syndrome • Abraham Lincoln? • Descendents of Lincoln’s great-great grandfather (8th generation) diagnosed with Marfan’s • Lincoln could have had a mild form of Marfan’s • Should we test Lincoln’s DNA?

21. Phenylketonuria (PKU) • Do not contain enzyme phenylalanine hydroxlyase (PAH) that breaks down amino acid phenylalanine into amino acid tyrosine • Phenylalanine builds up in brain • Toxic to central nervous system (CNS) • Mental Retardation • Tested at birth • PKU – 1/10,000 • U.S.  1/50 carry PKU allele • Regulated by Strict diet • Low protein: no meat, eggs, dairy • No Aspartame: sugar substitute sold as Equal or NutraSweet • Contains amino acid phenylalanine – 50%

22. Other Forms of Inheritance

23. Dihybrid Cross • Cross that involves two traits; more allele combinations possible; 4x4 Punnett Square • Ex: Peas  Green/Yellow & Round/Wrinkled • Ratio: 9:3:3:1

24. Multiple Alleles • 3 or more alleles for a single trait • EX:ABO blood groups – blood types • Characterized by the presence or absence of antigens • 4 Types: A, B, AB, o • A Blood has A antigen but no B, AB has both, O has neither • Represented by I (isoagglutination) • Codominant

25. Sex-Influenced Traits • Sex- Influenced: • Presence of male or female hormones influences the expression of the trait • Males and females with the same genotype will have different phenoypes • Ex: baldness; B=baldness, B’=normal hair • BB=bald (male/female) • B’B’=normal hair (male/female) • BB’= bald (male) normal (female)

26. Sex Linkage • Presence of gene on a sex chromosome (X or y) • X chromosome is larger than y  more genes carried on the X • X-Linked Genes:genes found on X chromosome • Appear mostly in males • Only one copy of X; nothing to counteract “bad gene” • Females would need two copies to express trait

27. Colorblindness • X-linked recessive • Cannot distinguish between different colors • Most common type is red/green colorblindness • Heterozygous females have mosaic retinas in which they have patches of color vision • Heterozygous female is considered a carrier

28. Hemophilia • X-linked recessive • Most Common in males • “Bleeder’s Disease” • Missing clotting factor • Bleeding spontaneously and in joints • Queen Victoria: descendents affected with hemophilia • Alexei Romanov

29. Duchenne Muscular Dystrophy • X-linked recessive • Most Common in males • 1/3500 • Muscle Enlargement • Dystrophin • Protein that provides support for the cell; without it, cell enlarges and explodes

30. Adrenoleukodystrophy • X-linked recessive • Most Common in males • “Lorenzo’s Oil” • Degradation of myelin sheath surrounding nerves (insulation) • Current News: • Oil not as effective as previously thought • Cholesterol lowering drug, Lovastatin seems to work • Bone Marrow Transplants work in some cases • Lorenzo Odone turned 27 on May 29, 2005 (Still completely paralyzed)

31. X-Inactivation • Barr Body • Only in females • Inactivated X chromosome • Random whether mom’s or dad’s X • Dark staining mass in nucleus • Allows for equal genetic expression between males and females (both express 1 X) • X-inactivation: • EX:Calico Cat • Coat color is X-linked recessive • Large patches of color (Black or orange) • Not in males because they only have 1 X

32. Genomic Imprinting • Genomic Imprinting: variation in phenotype expression depending on which parent gave the chromosome • Chromosome “remembers” which parent it came from • EX: Deletion of Chromosome 15 • Prader-Willi: uncontrollable eating, diabetes, mental retardation • Deletion of portion of paternal 15 • Angleman’s: behavior problems, some mental retardation • Deletion of portion of maternal 15

33. Holandric Traits • Holandric Traits: genes on the y chromosome; carry genes for male sexual characteristics • Absence of these genes causes female development • Small arm of y chromosome responsible for individuals that have a sex chromosome combination that does not match their appearance • XX males and XY females due to absence or presence of SRY factor • Ghengis Khan • Mongolian warrior 13th century • 8% of men living in region that was once Mongolian empire have same y chromosome

34. Mitochondrial DNA • mDNA inherited strictly from the mother • 600 bp region that is extremely different in unrelated individuals • Romanovs: • Tsar Nickolas II of Russia murdered during Bolshevik Revolution in 1918 • Remains identified by comparing mDNA to maternal descendants • Anna Anderson: pretended to be Anastasia • Proved false by mDNA

35. Marriage Line: Male: Carrier: Female: Offspring: Fraternal Twins: Identical Twins: Pedigree Charts • Pedigree:family record that shows how a trait is inherited over several generations • Shows both recessive and dominant traits • First Step in genetic counseling • Symbols:

36. Pedigree: English Royalty

37. Chromosomal Inheritance

38. Point Mutations • Gene Mutation: affects either one nucleotide or one codon • Substitution: one nucleotide is replaced with a different nucleotide resulting in a new codon • If new codon codes for same amino acid – no effect • If new codon codes for a different amino acid or stop codon – incorrect protein • Ex: Sickle Cell Anemia • Substitution: Adenine replaced by Thymine in a single codon; results in a defective form of hemoglobin • Frame-shift Mutation: caused by additions and deletions of one nucleotide; all codons after mutation are grouped incorrectly • Mutation at beginning of gene is worse than near the end of gene

39. Point Mutations

40. Chromosomal Mutations • Germ-Cell: occurs in gametes; only affect offspring • Somatic Cell: affects body cells; only affects organism • Lethal: causes death; often before birth (miscarriages) • Chromosome: changes to part or the whole chromosome; cannot be repaired by enzymes • Deletion: loss of a piece or whole chromosome • Inversion: segment of chromosome breaks off and reattaches in the reverse order on same chromosome • Translocation: piece of chromosome breaks off and reattaches to a nonhomologous chromosome • Down’s Syndrome: Trisomy 21; 3rd 21 can translocate to chromosome 13 (young mothers) • Duplication:part of chromosome attaches to homologous chromosome giving two copies of gene on that chromosome • Nondisjunction: failure of a chromosome to separate from its homologous chromosome during anaphase of meiosis; one gamete receives extra copy of chromosome other gamete does not receive one

41. Karyotype • Karyotype: chromosomes are stained and photographed under the microscope, cut from photo and arranged by size and shape; can detect chromosomal abnormalities • Monosomy: a zygote with only 45 chromosomes; one copy of a chromosome • Trisomy: three copies of a chromosome; 47 chromosomes total • Both result from nondisjunction

42. Down's Syndrome • Trisomy 21 • Mild to severe mental retardation • Distinct Facial Features • Heart Defects • Fingerprints – Sworl • Most Common Birth Defect – 1/700 births • Mother’s Age over 40 – 1/80 • Problems during Oogenesis

43. Klinefelter's Syndrome • Trisomy of sex chromosomes; XXy male • Feminine Characteristics, Infertile • George Washington? • No Children – Sterile? • Dental Problems • Height – Very tall for generation • Still Inconclusive

44. Turner's Syndrome • Monosomy of Sex Chromosomes; XO female • Infertile • Dwarfism • Overweight • Some mental retardation • Webbed Neck

45. Edward's Syndrome • Trisomy 18 • Elfin Appearance • Low set ears • Malformation of many organs – specifically heart/lungs • “Blue Babies” due to lack of oxygen • 90% die within first 6 months

46. Edward's Syndrome

47. Patau's Syndrome • Trisomy 13 • Cleft Lip and Palate • Polydactyl – more than ten fingers/toes • 1/6000 births • Most die within first year

48. Cri-du-chat • “Cat’s Cry” Syndrome • Deletion of a portion of Chromosome 5 • Mental Retardation

49. Reproductive Technology

50. Reproductive Technology • Invitrofertilization (IVF):“test tube babies” • Procedure: • Woman treated with fertility drugs to regulate menstrual cycle and develop high quality eggs • Eggs collected using a needle • Fertilization occurs in a Petri dish • Within 72 hours embryos transferred to uterus • Multiple births often occur • Artificial Insemination: fertilization occurs within uterus (in vivo) • Sperm inserted through a catheter passing through the cervix into the uterus