1. Human Genetics

2. Homunculus How is “heredity passed on”?: Spermist vs Ovists
Spermist conception of a human sperm… it contained a ”mini-me”!

3. Mendelian Genetics Gregor Mendel
Gregor Mendel was born on July 22, 1822, into a peasant family in a small town in Heinzendorf, Austria (now the Czech Republic), and spent much of his youth working in his family's orchards and gardens. (See Figure 1.2.) At the age of twenty-one he entered the Abbot of St. Thomas, an Augustinian monastery, where he studied theology, philosophy, and science. His interest in botany (the scientific study of plants) and aptitude for natural science inspired his superiors to send him to the University of Vienna to study to become a science teacher. However, Mendel was not destined to become an academic, despite his abiding interest in science and experimentation. In fact, the man who was eventually called the "father of genetics" never passed the qualifying examinations that would have enabled him to teach science at the highest academic level. Instead, he instructed students at a technical school. He also continued to study botany and conduct research at the monastery, and from 1868 until his death in 1884 he served as its abbot.
From 1856 to 1863 Mendel conducted carefully designed experiments with nearly 30,000 pea plants he cultivated in the monastery garden. He chose to observe pea plants systematically because they had distinct, identifiable characteristics that could not be confused. Pea plants were also ideal subjects for his experiments because their reproductive organs were surrounded by petals and usually matured before the flower bloomed. As a result, the plants self-fertilized and each plant variety tended to be a pure breed. Mendel raised several generations of each type of plant to be certain that his plants were pure breeds. In this way, he confirmed that tall plants always produce tall offspring and plants with green seeds and leaves always produce offspring with green seeds and leaves.
Read more: The History of Genetics - A Farmer's Son Becomes The Father Ofgenetics Study - Mendel, Plants, Tall, and Generation 3

4. Mendel’s Three Principles Dominance Segregation Independent Assortment
( )
The foundation of “classical” genetics
(Even though he didn’t know about genes!)

5. Dominance
Traits of both parents inherited, but one shows over the other
Traits are not blended

6. Dominance Mechanism
Two alleles are carried for each trait
In true-breeding individuals (pure breed), both alleles are the same
Hybrids, on the other hand, have one of each kind of allele
One trait is dominant, the other trait is recessive

7. Segregation
Each gamete (egg or sperm) will carry half the traits of one parent and half the traits for the other parent
23n
23n

8. Independent Assortment
Two different parental characteristics will be inherited independently of one another during gamete formation
- Dad could have an allele for brown hair AND blonde… these alleles end up being assorted in sperm independently
Example: eye, hair or skin color 8

9. Human Genome Project
U.S. govt. project coordinated by the Department of Energy and the National Institutes of Health, launched in 1986 by Charles DeLisi.
Definition: GENOME – the whole hereditary information of an organism that is encoded in the DNA
Project Goal: to identify the approximate 100,000+ genes in the human DNA
determine the sequences of the 3 billion bases that make up human DNA
store this information in databases
develop tools for data analysis
address the ethical, legal, and social issues that arise from genome research

10. Modeled Organisms whose genes we have sequenced
Bacteria (E. coli, influenza, several others)
Yeast (Saccharomyces cerevisiae)
Plant (Arabidopsis thaliana)
Fruit fly (Drosophila melanogaster)
Mouse (Mus musculus)

11. Importance of genetics
Understanding hereditary diseases and to develop new treatments
Donor matches
Paternity
Forensics
Evolution
Migration

12. Genetic Testing Would you want to know? Ethical concerns Cost
Insurance companies

14. Autosomes & Sex Chromosomes

15. Difference between Meiosis and Mitosis

16. Meiosis I
Interphase
Prophase I
Metaphase I
Anaphase I
Telephase I

17. Crossing Over of Nonsister Chromatids between Homologous Chromosomes

18. Meiosis II
Prophase II
Metaphase II
Anaphase II
Telephase II

20. X Y
X-bearing sperm
Y-bearing sperm X X
Egg
Egg
XX Female
XY Male

22. Sex Determination Maleness derived from Y chromosome - Dad determines!
Female reproductive structures degenerate
Lecture 28

23. Genes of the Sex Chromosome
Has over 1500 genes
Most genes on X don’t have corresponding alleles on the Y chromosome
Y chromosome
Has about 200 genes
Some genes are unique only to the Y

24. Sex Chromosomal Disorders
Turner Syndrome – X only one sex chromosome
Short, thick neck and stature
Do not undergo puberty, or menstruate,
No breast development
Kleinfelter Syndrome – XXY
Testis and prostate underdeveloped
No facial hair
Breast development
Long arms and legs: big hands and feet
Can be mentally retarded

25. XXY XO

26. Genetic Testing
30 year old woman with early onset alzheimer’s had eggs selected that did not have alzheimer’s

27. Gel electrophoresis
The gel electrophoresis method was developed in the late 1960's. It is a fundamental tool for DNA sequencing.

28. Polymerase Chain Reaction
PCR way of copying specific DNA fragments from small sample DNA material "molecular photocopying"
It’s fast, inexpensive and simple
Sometimes called the polymerase chain reaction (PCR) is a fast and inexpensive technique used to "amplify" - copy - small segments of DNA. Because significant amounts of a sample of DNA are necessary for molecular and genetic analyses, studies of isolated pieces of DNA are nearly impossible without PCR amplification.
Denature. The first step requires a high temperature to denature the dsDNA. This is typically done by briefly heating the sample to 92-94oC.
Anneal. The second step requires lowering the temperature to allow annealing of the primers to the ssDNA. The optimal annealing temperature depends upon the melting temperature of the primer-template hybrid. If the temperature is too high the primers will not anneal efficiently, and if the annealing temperature is too low the primers may anneal nonspecifically. Annealing is usually done, at 5oC below the Tm of the primers, typically about 45-55oC. (As a simple rule of thumb, the Tm of the primers can be estimated by adding 2oC for each A or T and 4oC for each G or C.) Because the primers are in vast excess to the template, the annealing reaction occurs very quickly once the proper temperature has been reached. To insure adequate specificity, the primers must be nucleotides long.
Extend. The third step requires DNA synthesis by DNA polymerase. To withstand the repeated exposure to high temperatures, a thermostable DNA polymerase is used for PCR. A variety of thermostable DNA polymerases (isolated from different thermophilic Bacteria or Archae) are available, but the first thermostable DNA polymerase used for PCR, called Taq polymerase, was isolated from the bacterium Thermus aquaticus. The optimal temperature for Taq polymerase is about 75-80oC, but it is partially active even at typical annealing temperatures so primer extension begins during the annealing step. The rate of primer extension by Taq polymerase is about nucleotides/sec. Thus, the time required for primer extension depends on the length of the sequence to be amplified.

30. Genetic Definitions
Genes- genetic material on a chromosome that codes for a specific trait
Genotype- the genetic makeup of the organism
Phenotype- the expressed trait
Allele- an alternative form of a gene

31. Dominance Mechanism Two alleles are carried for each trait
In true-breeding individuals, both alleles are the same (homozygous).
Hybrids, on the other hand, have one of each kind of allele (heterozygous).
One trait is dominant, the other trait is recessive

32. Genetic Information Genes are traits “Eye color”
Ear lobe connectedness
Genes produce proteins
Enzymes are proteins

33. Homologous Chromosomes
gene: location
allele: specific trait

34. Allele Example
Gene = “eye color”
Alleles
brown
blue
green
lavender

36. Allele Examples
appearance B B
eye color: homozygous

37. Allele Examples appearance eye color: heterozygous,B b
eye color: heterozygous,
brown dominant over blue

38. Genotype vs Phenotype genotype phenotype homozygous (dominant)
heterozygous
homozygous
(recessive) B B B b b b
appearance

39. Punnett Square If male & female are heterozygous for eye color male BX B b B b b b b
brown: 3/4 offspring
blue: 1/4 offspring

40. Each parent carries one gene for PKU.X P p P
How is PKU inherited?
Phenylketoneuria (PKU) affects people who inherit two copies of an altered gene from their carrier parents. Carrier parents have a one-in-four chance of having an affected child, a one-in-two chance of having a child who is an unaffected carrier and a one-in-four chance of having a child with no altered genes at all. Carriers of PKU are not affected themselves, as they have a working gene as well as an altered one.
If some genes 'cause' PKU and Huntington's chorea why haven't they been removed from our species by the process of natural selection?
1. PKU is an autosomal recessive disorder with an incidence of 1 in 5,000 homozygous (carrying two copies of the mutation) affected people in Celtic populations. Using the Hardy Weinberg equation we can calculate that 1/36 of the population are healthy heterozygotes carrying only 1 copy of the PKU mutation. The vast majority of PKU alleles in the population are in  healthy carriers. Even if all the PKU alleles in the relatively small affected population are removed from the whole population each generation (because affected people do not reproduce) then it would take very many generations to reduce the total frequency of the gene in the population. As the gene became rarer then the chance two carriers would meet would reduce so the number of affected offsprings' PKU alleles that would be removed from the population would also go down. Very complex, a computer model would help!
In practice other factors will also be at work; e.g. treated PKU patients can now have families and their genes will maintain or increase the PKU mutation pool. 
Why is the PKU gene so common in the Celtic population? We do not know. Maybe if the population was founded by a relatively small number of individuals and by chance one carried a PKU mutation, the resulting high PKU incidence would be maintained as the population grew. Perhaps the carriers have a greater reproductive fitness than the non carriers; c.f. sickle cell disease in malarial areas. See the following for more details: GENETICS
2. Huntington disease is an autosomal dominant disease causing progressive dementia and a movement disorder. The mutation is caused by a length expansion of a trinucleotide repeat sequence in the Huntingtin gene.  It is likely that the vast majority of cases in the world are descended from a relatively small number of founder mutations. One founder mutation has arisen in Western Europe and spread with European colonisation, another has arisen in Japan. Although Huntington disease is ultimately fatal, it is a late onset disease and does not seem to affect reproductive fitness. Indeed, many clinical geneticists have an  impression that affected patients have larger families than their unaffected relatives. This was confirmed in a study of the Northern Irish population by Morrison et al., 1995,  J. Med. Genet. 32: Some molecular studies of human and primate populations has suggested that the key element in HD evolution is a tendency to ever-lengthening repeats in the normal population and this will lead to an ever-increasing incidence of HD. See the following for more details: GENETICS p p p p
Possible genotypes: 1PP 2Pp 1pp
Possible phenotypes:no PKU PKU

41. Compare this to what would have happened if one parent was homozygous for sickle cell.
HbA
HbA
HbA
HbA
HbS
HbA
HbA
HbS
HbS X
HbA
HbA
HbS
HbS
HbS
HbS
HbS
all offspring are carriers of sickle cell trait

42. Where Does Genetic Diversity Come From?
Mutations (any change in the DNA sequence)
Chromosomal Aberrations/Mutations
Genetic Recombination (e.g., from sexual reproduction)

43. Sickle Cell Mutation CTG ACT CCT GAG GAG AAG TCT
NORMAL Hb
CTG ACT CCT GAG GAG AAG TCT
Leu Thr Pro Glu Glu Lys Ser
SICKLE CELL
CTG ACT CCT GAG GTG AAG TCT
Leu Thr Pro Glu Val Lys Ser
mutation

44. Autosomes and Sex Chromosomes

45. Red-Green Color Blindness
Sex-linked trait XC Y XC Y XC XC XC
Normal male XC Y X XC Xc XC Xc Xc Xc Y
Normal female recessive gene
Possible outcomes: XCXC XCXc XCY XcY
Normal
female
Normal
Female
(carrier)
Normal
male
Color-blind male

46. E unconnected earlobe e connected earlobe P EE x ee E e F1 Ee allele
gene
E unconnected earlobe
e connected earlobe
unconnected P
EE x ee
gametes
E e
connected F1 Ee

47. F1 Ee x Ee 1/2 E 1/2 e 1/2 E 1/2 e E e E EE Ee e Ee ee F2
gametes E e E EE Ee
Punnett Square e Ee ee F2
1 EE 2 Ee 1 ee

48. Genotypes Phenotypes
Experiment to determine dominant vs. recessive

49. Genetic Sleuthing My eye color phenotype is brown.
What is my genotype?

50. Complexities Multiple genes for one trait Example: eye color
Blended traits (“incomplete dominance”)
Influence of the environment (UV, smoking, alcoholism)

51. Complexities
Co-dominance-neither allele is recessive and the phenotypes of both alleles are expressed.
Blood types- AB (not O); sickle cell anemia
heterochromia

52. Disorders Down’s Syndrome (chrom 21)
Alzheimer’s (chrom 1, 10, 14, 19, 21)
Huntington’s (chrom 4)

53. Human Genetic Traits

54. R = Tongue Roller r = Unable to Roll Tongue

55. W = Widows Peak w = Lack of Widow’s Peak

56. E = Free Ear Lobe e = Attached Ear Lobe

57. Hi = Straight Thumb hi = Hitchhiker’s Thumb

58. Bf = Bent Little Finger bf = Straight Little Finger

59. M = Mid-Digital Hair m = Absence of Mid-Digital Hair

60. D = Dimples d = Absence of Dimples

61. Ha = Short Hallux ha = Long Hallux

62. Ss = Short Index Finger S1 = Long Index Finger
*Sex-Influenced Trait

63. Blaze
B = blaze
b = no blaze