Lakshmi put the results in a table: Asia Europe Africa N. America

Step 2: Create a Table to Analyze Your Data and Calculate the Chi Square Value
Lakshmi put the results in a table: Asia Europe Africa N. America S. America Australia Antarctica Expected 1,000,000 Observed 5,000,000 500,000 100,000 800,000

oi = observed/measured value i ei = experimental value i
Step 2: Create a Table to Analyze Your Data and Calculate the Chi Square Value The formula for chi square value is as follows: χ2 = Σ(oi - ei)2 / ei oi = observed/measured value i ei = experimental value i Σ = sum of values i = 1, 2, etc. up to number of conditions

Sample calculation (oi - ei)2 / ei = 16,000,000
(5,000, ,000,000)2 / (1,000,000) (4,000,000)2 / 1,000,000 = 16,000,000 Asia Expected 1,000,000 Observed 5,000,000

Calculating chi square
Asia Europe Africa N. America S. America Australia Antarctica Expected, e 1,000,000 Observed o 5,000,000 500,000 100,000 800,000 (oi - ei)2 / ei 16,000,000 250,000 810,000 40,000 10,000,000 χ2 = Σ(oi - ei)2 / ei = 28,160,000

Step 3: Calculate degrees of freedom
Now, we must calculate degrees of freedom based on the formula DF = # of conditions - 1

Step 3: Calculate degrees of freedom
There are seven conditions (the seven continents). 7 - 1 = 6. There are six degrees of freedom.

Step 4: Determine Significance Level
If the p-value is less than 0.05, the chi square test supports your alternate hypothesis If the p-value is greater than 0.05, the chi square test supports the null hypothesis The 0.05 represents a percentage (5%) chance that the results are due to chance, not reproducible, and statistically incorrect

Step 5: Using a Distribution Table to Determine the X2 Critical Value
Degrees of freedom p = 0.05 Critical value =

Which hypothesis is true?
χ2 = 28,160,000, which is much greater than the critical value, The null hypothesis can be rejected. The data is not consistent with the expected result. Lakshmi is delighted that Evan was wrong.

Try it!

Chi-squared test Interactive activity!! FUN FUN!!!!!

Gene Linkage 14

Dihybrid Cross with Linkage
Genetic linkage particular alleles inherited together Alleles on the same chromosome are more likely to be inherited together, and are said to be linked. 15

Mendelian ratios Monohybrid Dihybrid
when parental type is AA x aa what is the phentypic ratio of f1? F2? Aa X aa – f1? Dihybrid - when parental type is AA/BB x aa/bb are crossed what is the phenotypic ratio of f1? F2? - AaBb x aabb – f1? 16

Thomas Hunt Morgan The Nobel Prize in Physiology or Medicine 1933
"for his discoveries concerning the role played by the chromosome in heredity" USA California Institute of Technology Pasadena, CA, USA b d. 1945 17

Gene Linkage Genes on the same chromosome are said to be linked
they tend to be inherited together 18

linkage Wild type fruit fly Grey body and normal wings G = gray
g = black (mutant) L = long wings l = short wings 19

The cross GgLl heterozygous gray with long wings X
ggll (mutants black bodies short wings) Gametes would be GL, Gl, gL, gl x gl 20

According to Mendel This cross should have produced a ratio of 1:1:1:1
1 gray long wing 1 black short wing 1gray short wing 1 black long wing 21

What did he really get? Gg Ll = 965 (wild type- gray, long winged)
gg ll = (black - short wing) Gg ll = (gray short wing) gg Ll = (black long wing) Morgan reasoned that body color and wing shape are usually inherited together in a specific combination. The genes are located on the same chromosome 22

So what could it be? All the phenotypes are represented and new combinations are due to crossing over. 23

Crossing over in Prophase I of Meiosis
24

Genetic Recombination
exchange of alleles between homologous chromosomes alleles of parental linkage groups separate and new associations of alleles are formed in the gametes recombinants Off spring showing this new combination 25

Example recombination
In peas…. Seed coat and seed shape are unlinked Cross YyRr yellow round With yyrrr green wrinkled 26

What did he see? ¼ YyRr yellow round ¼ yyrr green wrinkled
¼ yyRr green round ¼ Yyrr yellow wrinkled 27

So…………. ½ have parental phenotypes yellow round and green wrinkled
Because the other offspring have different combinations of seed shape and color then their parents they are recombinants 28

Crossing over Linked genes do not sort independently Why?
But recombination does exist between linked genes how? because they are located on the same chromosome and tend to move together through meiosis and fertilization 29

Take another look GgLl = 965 (wild type-gray long winged)
gg ll = (black - short wing) Gg ll = (gray short wing) gg Ll = (black long wing) Morgan reasoned that body color and wing shape are usually inherited together in a specific combination. The genes are located on the same chromosome 30

How would you denote a heterozygous genotype for linked alleles?
Linkage notation The two horizontal bars symbolize homologous chromosomes and show that the locus of G is on the same chromosome as L. One G is on the maternal homolouge and the other G is on the paternal homologue. G L G L g l What does the symbol to the left mean? How would you denote a heterozygous genotype for linked alleles? 31

Back to the example: In this case
What percentage of offspring did not have parental phenotype? Morgan hypothesized that there must be some mechanism which allowed for the exchange of segments between homologous chromosomes. He called it Crossing Over…. 17% 32

Now enters Alfred Sturterant, a student of Morgan’s
33

Sturtevant (1917) hypothesis
Different recombination frequencies reflect different distances between genes on a chromosome. Or If two genes are far apart on a chromosome there is a higher probability that a crossover event will separate them than if the two genes are close together 34

Frequency of crossover exchange
Frequency of crossover exchange... of chromatids of a homologous pair at synapsis forming a chiasmata... Frequency is GREATER the FARTHER apart 2 genes are proportional to relative distance between 2 linked genes Relative distance is established as... 1% crossover frequency = 1 map unit of map distance 1% CrossOver Freq = 1 centiMorgan (cM) 35

An example of linkage Start with two different strains of corn (maize). one that is homozygous for two traits yellow kernels (C,C) smooth (Sh,Sh). a second that is homozygous for colorless kernels (c,c) wrinkled because their endosperm is shrunken (sh,sh) 36

then After pollination all the F1 are yellow and smooth.
So what is dominant? the alleles for yellow color (C) and smoothness (Sh) are dominant over those for colorlessness (c) and shrunken endosperm (sh). How do we know this? 37

What should the results be? Why?
Do a test cross Which is? What should the results be? Why? 38

What does the chart show?
If the inheritance of these genes observes Mendel's second rule; i.e., shows independent assortment, union of these gametes should produce approximately equal numbers of the four phenotypes. What does the chart show? It occurs because the two loci are relatively close together on the same chromosome. Which are the recombinants? What percentage are recombinants? What happened? Why do we see any recombinants? 40

again During prophase I of meiosisDuring prophase I of meiosis, pairs of duplicated homologous chromosomes unite in synapsis and then nonsister chromatids exchange segments during crossing over. It is crossing over that produces the recombinant gametes. In this case, whenever a crossover occurs between the locus for kernel color and that for kernel texture, the original combination of alleles (CSh and csh) is broken up and a chromosome containing Csh and one containing cSh will be produced. 41

Chromosome maps Recombinants are used to make chromosome maps
That is how they figure out how far apart alleles are But you are not responsible for chromosome mapping But I can show you how it is done, just for fun :) In other words, you will not be tested on anything past this slide. 43

Chromosome Maps The percentage of recombinants formed by F1 individuals can range from a fraction of 1% up to the 50% always seen with gene loci on separate chromosomes (independent assortment). The higher the percentage of recombinants for a pair of traits, the greater the distance separating the two loci. In fact, the percent of recombinants is arbitrarily chosen as the distance in centimorgans (cM), named for the pioneering geneticist Thomas Hunt Morgan. In our case, the c and sh loci are said to be 2.8 cM apart. 44

Example Test crossing a corn plant that is dihybrid for the C,c alleles and the alleles for bronze color (Bz, bz) produces 4.6% recombinants. So these two loci are 4.6 cM apart. However, is the bz locus on the same side of c as sh or is it on the other side? 45

The answer can be found by test crossing the dihybrid Shsh, Bzbz.
If the percentage of recombinants is less than 4.6%, then bz must be on the same side of locus c as locus sh. If greater than 4.6%, it must be on the other side. In fact, the recombination frequency is less than 1.8%, telling us that the actual order of loci is c- sh- bz. 46

A genetic map of chromosome 9 (the one that carries the C, Sh, and bz loci) of the corn plant (Zea mays) is shown on the right. 47

Recombination frequencies reflect the distances between genes on a chromosome.
The farther apart two genes are, the more likely that a crossover will occur between them and hence the higher the recombination frequency. A genetic map, called a linkage map, can be constructed based on recombination frequencies. 1 map unit , called a centimorgan, equals a 1% recombination frequency. `` 48

A “simple” map 49

Gene linkage Practice problems

In your Nature’s dice groups make a 1% gel
40 mL of TBE buffer and .4 grams of agarose microwave Add 4 microliters of SYBR safe DNA stain (at my desk) pour (8 well comb) Let gel solidify and while solidifying: Review HW Set up gel electrophoresis station and gather all supplies Ladder (HindIII lambda) DNA samples from refrigerator You need to add loading dye Set up gel sketch marking each lane Run gel at 120 volts Come back to desk for lesson

Alternate Patterns of Inheritance
57

Why was Mendel lucky? Or was he?
58

Incomplete dominance Our pink flowers are not required for IB
A moment of silence …. Really, what IB has done is eliminated the term incomplete dominance, it is now together with codominance 59

Codominance Codominant alleles: pairs of alleles that both affect the phenotype when present in a heterozygote. Like: Pink flowers And Roan cows 60

Codominance Use the trait as the letter and then use a superscript for the characteristic But BE CAREFUL- use only 2 letters, the heterozygote must have both letters Example: Red flower CRCR White flower CWCW Pink flower CRCW 61

Codominance Punnett Squares
When doing a punnett square involving codominance Choose the homozygotes first Red cow - CRCR White cow - CWCW Then make the heterozygotes Roan cow - CRCW Remember that you follow the same rules for a blending of traits, only we don’t call it incomplete dominance, it is called codominance for IB 62

Sample Questions Predict the phenotypic ratios of offspring when a homozygous white cow is crossed with a roan bull. 2. A cross between a black cat & a tan cat produces a tabby pattern (black & tan fur together).   a) What pattern of inheritance does this illustrate? Why? b) What percent of kittens would have tan fur if a tabby cat is crossed with a black cat? 63

Predict the phenotypic ratios of offspring when a homozygous white cow is crossed with a roan bull.
50% white, 50 %roan 2. A cross between a black cat & a tan cat produces a tabby pattern (black & tan fur together). a) What pattern of inheritance does this illustrate? Why? Codominance – both phenotypes present in heterogygous b) What percent of kittens would have tan fur if a tabby cat is crossed with a black cat? None CW CWCW CR CWCR B T BB BT

State that some genes have more than two alleles (multiple alleles).
Traits controlled by more than two alleles are said to have multiple alleles. A diploid individual can possess only two alleles of each gene. Why? Therefore multiple alleles can be studied only in populations. So far we have studied patterns of heredity in which each trait has only two alleles. It is common for more than two alleles to control a trait in a population. 65

. The number of alleles for any particular trait is not limited to four, there are instances in which more than 100 alleles are known to exist for a single trait 66

Multiple Alleles Multiple Alleles govern blood type
blood types are determined by the presence or absence of certain molecules on the surfaces of red blood cells (antigens). As the determinant of blood type the gene I has three alleles: IA, IB , and i, often written A, B, and O. The IA allele produces antigen A, the IB allele produces antigen B, i produces no antigens. 67

IA and IB are dominant to i IA and IB are co-dominant to each other.
Describe ABO blood groups as an example of codominance and multiple alleles. IA and IB are dominant to i IA and IB are co-dominant to each other. 68

Ever wonder why you certain blood types cannot be mixed?
It has to do with antigens and antibodies. Antibodies attack antigens. A antigen produces antibodies for antigen B B antigen produces antibodies for A AB has no antibodies- why? O has no antigens We will discuss this more when we cover the immune system. 69

Importance of Blood Typing
Incompatible blood types could clump together, causing death. Disputed parentage Example: If a child has type AB blood and its mother has type A, a man with type O blood could not be the father. Why? 71

Practice A woman with Type O blood and a man who is Type AB are expecting a child. What are the possible blood types of the kid? What are the possible blood types of a child who's parents are both heterozygous for "B" blood type? What are the chances of a woman with Type AB and a man with Type A having a child with Type O? Determine the possible genotypes & phenotypes with respect to blood type for a couple who's blood types are homozygous A & heterozygous B. Jill is blood Type O. She has two older brothers with blood types A & B.What are the genotypes of her parents with respect to this trait? A test was done to determine the biological father of a child.The child's blood Type is A and the mother's is B. Man #1 has a blood type of O, & Man #2 has blood type AB. Which man is the biological father? 72

A woman with Type O blood and a man who is Type AB have are expecting a child. What are the possible blood types of the kid? A, B What are the possible blood types of a child who's parents are both heterozygous for "B" blood type? B,O What are the chances of a woman with Type AB and a man with Type A having a child with Type O? None IA IB i IA i IB i IB i IB IB IB i i i IA IB IA IA IA IB IA IB IA IA IA IB i IA i IB i 73

Determine the possible genotypes & phenotypes with respect to blood type for a couple who's blood types are homozygous A & heterozygous B. AB, A Jill is blood Type O. She has two older brothers with blood types A & B.What are the genotypes of her parents with respect to this trait? IA i x IB i A test was done to determine the biological father of a child.The child's blood Type is A and the mother's is B. Man #1 has a blood type of O, & Man #2 has blood type AB. Which man is the biological father? Man #2 IA IB IA IB i IA i 74

Sex linkage Autosomes are the chromosomes that are the same in each sex Sex chromosomes determine sex of individual XX in females, XY in males X chromosome also has genes for many traits NOT associated with sexual characteristics 75

Sex linked inheritance patterns: Genes on the sex chromosomes have different inheritance patterns
If gene is on Y chromosome Sons will inherit from father Females don’t get Y-linked traits Y-linked genes not common Hairy ears is one example If gene is on X chromosome Can inherit from either parent But sons always get from mom because she gives an X chromosome to sons 76

Human examples of X-linked traits
Color blindness Hemophilia Duchene muscular dystrophy (SCID) Severe Combined Immunodeficiency Syndrome (boy in the bubble disease) Adrenoleukodystrophy- Lorenzo’s Oil 77

X-linked recessive genes
Females can be carriers Have gene, but do not show trait Other X has normal dominant gene Males cannot be carriers, they have it or they do not. Male determines sex - either gives X or Y Will give gene to all daughters, none to sons If he has the gene all his daughters will be carriers of trait 79

X-linked inheritance If a trait is X-linked, males pass on the X-linked allele to all of their daughters and none of their sons. Heterozygous females have a 50% chance of passing on a recessive X-linked allele to each child. If a son receives an X chromosome with a recessive allele from his mother, he will express the recessive phenotype because he has no chance of inheriting from his father a dominant allele that would mask the recessive. 80

How could females express X-linked trait?
81

Red-green color blindness
An X-linked disorder Can’t differentiate these two colors. Many people who have this are not aware of the fact. What serious consequence could result from this? Red-green color blindness was first described in a young boy who could not be trained to harvest only the ripe, red apples from his father’s orchard. Instead, he chose green apples as often as he chose red. 82

1. Normal Color Vision: A: 29, B: 45, C: --, D: 26
Sex-Linked Traits: 1. Normal Color Vision: A: 29, B: 45, C: --, D: 26 2. Red-Green Color-Blind: A: 70, B: --, C: 5, D: -- 3. Red Color-blind: A: 70, B: --, C: 5, D: 6 4. Green Color-Blind: A: 70, B: --, C: 5, D: 2 83

Hemophilia An X-linked disorder that causes a problem with blood clotting If your blood didn’t have the ability to clot and you bruised yourself or scraped your knee, you would be in danger of bleeding to death. Queen Victoria ( ) Queen Victoria of England was a carrier of the gene for hemophilia. She passed the harmful allele for this X-linked trait on to one of her four sons and at least two of her five daughters. Her son Leopold had the disease and died at age 30, while her daughters were only carriers. As a result of marrying into other European royal families, the princesses Alice and Beatrice spread hemophilia to Russia, Germany, and Spain. By the early 20th century, ten of Victoria's descendents had hemophilia. All of them were men. 84

Males only have one X-chromosome .
About one male in every 10,000 has hemophilia, but only about one in 1 million females inherits the same disorder. Why???? Males only have one X-chromosome . A single recessive allele for hemophilia will cause the disorder. Females would need two recessive alleles to inherit hemophilia. Males inherit the allele for hemophilia on the x-chromosome from their carrier mothers. (Why not from their father?) 85

How to set up a sex linked punnett square
86

Practice XR=red eyes Xr= white eyes
What are the possible genotypes for females? What are the possible genotypes for males? Which cross would produce white eyed males : a) XRXR x XrY or b) XRXr x XRY? 87

XR=red eyes Xr= white eyes
What are the possible genotypes for females? What are the possible genotypes for males? Females – XRXR, XRXr, XrXr Males – XRY, XrY Which cross would produce white eyed males : a) XRXR x XrY or b) XRXr x XRY? b

????? Both the mother and the father of a male hemophiliac appear normal. From whom did the son inherit the allele for hemophilia? What are the genotypes of the mother, the father and the son? A woman is color blind. If she marries a man with normal vision, what are the chances that her daughter will be color blind? Will be carriers? What are her chances that her sons will be color blind? Is it possible for two normal parents to have a color blind daughter? 89

Mom = XHXh Dad = XHY Son = XhY
Both the mother and the father of a male hemophiliac appear normal. From whom did the son inherit the allele for hemophilia? What are the genotypes of the mother, the father and the son? Mom = XHXh Dad = XHY Son = XhY A woman is color blind. If she marries a man with normal vision, what are the chances that her daughter will be color blind? Will be carriers? What are her chances that her sons will be color blind? 0% colorblind daughters 100 % colorblind sons Is it possible for two normal parents to have a color blind daughter? NO

There are two types of Zom Bee, one with red legs and one with blue legs. The characteristic is carried on the X chromosome. If red is dominant, what is the F2 ratio if red-legged female bees are crossed with blue-legged males, the F1 males all being red-legged?

XR Xr XRXR XRXr Y XRY XrY XR Xr XRXr Y XRY

Epistasis When one gene masks the effect of a different gene.
Not dominant/recessive because it is a different gene locus Dominance A masking a Epistasis ee masking AA or Aa 93

Coat color - Labrador retrievers
Epistasis example: Coat color - Labrador retrievers Gene 1 - production of pigment BB - Black Bb - black bb - chocolate Gene 2 - pigment deposition EE or Ee - pigment deposited ee - no pigment deposited 94

BBEE BBEe BbEE BbEe BBee Bbee bbee bbEE bbEe 95

BbEe X BbEe BE Be bE be BBEE BBEe BbEE BbEe BBee Bbee bbEE bbee bbEe
96

Polygenic inheritance
Poly = many, genic = genes More than one gene pair contributes to a phenotype Effects of dominant alleles are additive More dominant genes - increased effect Number of dominant determines phenotype Hair, eye and skin color are polygenic traits Many disorders may be polygenic Cleft palate, club foot, diabetes, schizophrenia, allergies, cancer 97

Polygenic inheritance
One trait related to many genes Skin, hair and eye color, height If skin color was related to 3 gene pairs Dominant gene A, B or C produces pigment Incompletely dominant to a, b or c So # of dominant genes determines how much pigment is produced AABBCC = lots of pigment aabbcc = very little pigment AaBbCc = middle range of pigment 2 heterozygotes (AaBbCc) could have a child with any pigment range 99

My own family – an example of polygenic inheritance

What about height? height/

Continuous vs. Discontinuous Variation
Draw a graph of the phenotypes following traits: Plant height Blood types Cow coat color Skin Color 102

Environmental Influences
The environment also influences the expression of genes. Temperature and Siamese cats The darker colors on the extremities are due to a cooler body temperature. The gene that codes for production of the color pigment in the Siamese cat only functions under cooler conditions. 103

Pedigree Analysis

Pedigree analysis tool for studying inherited diseases uses family trees and information about affected individuals to: figure out the genetic basis of a disease or trait from its inheritance pattern predict the risk of disease in future offspring in a family (genetic counseling)

Pedigree analysis How to read pedigrees Basic patterns of inheritance autosomal, recessive autosomal, dominant X-linked, recessive X-linked, dominant (very rare) Applying pedigree analysis - practice

Sample pedigree - cystic fibrosis
female male affected individuals

Autosomal Recessive Examples: -Cystic Fibrosis -Sickle Cell Anemia
-Tay-sachs Appearance on a pedigree: Trait skips generations Trait affects both males and females equally Trait is rare among a pedigree

Cystic Fibrosis Life-threatening that primarily affects lungs and digestive system Defective gene causes body to produce unusually thick, sticky mucus Eventually clogs the lung

Autosomal Dominant

Huntington’s Disease Is Huntington’s dominant/recessive, autosomal/sex-linked?

Autosomal dominant traits
There are few autosomal dominant human diseases (why?), but some rare traits have this inheritance pattern ex. achondroplasia (a sketelal disorder causing dwarfism)

X-linked recessive pedigrees
Trait is rare in pedigree Trait skips generations Affected fathers DO NOT pass to their sons, Males are more often affected than females

ex. Hemophilia in European royalty
X-linked recessive traits ex. Hemophilia in European royalty

X-linked dominant pedigrees
Trait is common in pedigree Affected fathers pass to ALL of their daughters Males and females are equally likely to be affected

X-linked dominant diseases
X-linked dominant diseases are extremely unusual Often, they are lethal (before birth) in males and only seen in females ex. incontinentia pigmenti (skin lesions) ex. X-linked rickets (bone lesions)

Pedigree Analysis in real life:
complications Incomplete Penetrance of autosomal dominant traits => not everyone with genotype expresses trait at all Ex. Breast cancer genes BRCA-1 and BRCA-2 & many “genetic tendencies” for human diseases

Pedigree Analysis in real life: complications
Sex-limited expression => trait only found in males OR females

Pedigree Analysis in real life
Remember: dominant traits may be rare in population Six fingers recessive traits may be common in population alleles may come into the pedigree from 2 sources mutation happens often traits are more complex affected by environment & other genes

The pedigree below traces the inheritance of a biochemical disorder
The pedigree below traces the inheritance of a biochemical disorder. Does the disease appear to be caused by a dominant or recessive allele? Fill in the genotypes of the individuals whose genotypes you know. What genotypes are possible for each of the other individuals?

Autosomal Recessive

The pedigree below traces the inheritance of a vary rare biochemical disorder in humans. Affected individuals are indicated by filled-in circles and squares. Is the allele for this disorder dominant or recessive?

Autosomal Dominant 1 = Aa 2 = Aa 3 = aa

What is the pattern of inheritance?
What are IV-2’s odds of being a carrier?

2/3 Chance of being a carrier
What is the pattern of inheritance? What are IV-2’s odds of being a carrier? Autosomal recessive 2/3 Chance of being a carrier

Sample pedigree - cystic fibrosis
What can we say about I-1 and I-2? What can we say about II-4 and II-5? What are the odds that III-5 is a carrier? What can we say about gene frequency?

What can we say about I-1 and I-2?
- they are carriers What can we say about II-4 and II-5? What are the odds that III-5 is a carrier? - 2/3 What can we say about gene frequency? - rare, seems to skip a generation

What is the inheritance pattern?
What is the genotype of III-1, and III-2?

What is the inheritance pattern
What is the inheritance pattern? X- linked recessive What is the genotype of III-1, and III-2? XHY, XHXh

Which inheritance pattern best describes the genetics of the afflicting allele in the following pedigree (it is a pedigree of taste blindness)?

Autosomal recessive

For the following pedigree, how does the afflicting allele impact on phenotype?

Autosomal Dominant

Albinism is inherited as an autosomal recessive
Albinism is inherited as an autosomal recessive. In the figure below, assuming that persons from the general population are not heterozygous for albinism (Aa), what are the genotypes of all persons whose genotypes are known? (i.e., indicate the genotypes on the figure for all known AA, Aa, and aa individuals)

In the figure below, all individuals from the general population (i. e
In the figure below, all individuals from the general population (i.e., married in spouses) are AA. All circled individuals are Aa. All afflicted individuals are aa.

Given the pedigree, would you expect to find more of in Cleopatra-Berenike III compared with the general population? 1.Loci which are heterozygous 2.Loci which are homozygous for rare alleles 3.Loci which display epistasis 4.Loci which display codominance 5.Alleles 6.Loci

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