Exam 3 Flashcards
What is a null hypothesis?
A null hypothesis assumes data will fit a given ratio or model, and that any variation is purely by chance.
True or False:
A null hypothesis can be proven.
False:
A null hypothesis cannot be proven, but it can be either supported (failed to reject) or rejected.
What does the Chi-square statistical test accomplish?
Known as the ‘goodness of fit’ test, it evaluates the influence of chance on data and assesses whether the data is consistent with the model (expected outcome) and determines if the null hypothesis should be rejected or not.
What is p-value (Chi-square test calculation)?
P-value is a statistical measure of significant differences between datasets calculated using a Chi-square statistical test and has a cut-off (a) frequently set to 0.05.
What does the value (i.e. 0.5) of p-value mean?
The value (0.5) obtained from calculating p-value is the percent (5%) that if this experiment is repeated, there is a 5 percent chance that the same or greater variation in data would be observed again.
When should one reject or accept the null hypothesis based on the p-value?
If the p-value of the data is greater than the cut-off (a) then the null hypothesis is supported. However, if the p-value of the data is less than the (a) then the null hypothesis is rejected due to too much variation.
How do you determine how many degrees of freedom?
Degrees of freedom are determined by taking the sum of how many variants are being analysed and subtracted by one.
Example: Vestigial wings are completely recessive to wild-type wings in Drosophila melanogaster.
Monohybrid cross data:
315 F2 flies with wild-type wings
97 F2 flies with vestigial wings
Model?
Null Hypothesis?
(X^2)?
Degrees of Freedom?
p-value?
Fail to reject or reject?
Model? 3:1
Null Hypothesis? There is no difference between the monohybrid cross results and the model; the monohybrid results follow a 3:1 ratio.
(X^2)?
X^2 = sum of ((Observed - Expected)^2) / Expected
wild-type: 315 309 0.117
vestigial: 97 103 0.350
412
Sum (wild-type + vestigial X2) = 0.467 = X2
Degrees of freedom? 1
p-value? 0.50
Fail to reject or reject? Fail to reject
Gene mapping
What is linkage?
Genes (alleles) on the same chromosome are likely to be inherited together known as linked genes.
Gene mapping
What is a linkage group and provide an example?
A linkage group is a set of linked genes.
(i.e. Genes located on chromosome 4 are in linkage group IV; Genes located on the X chromosome are X-linked)
Gene mapping
What is a genetic map?
A genetic map shows the order of linked genes and distances between genes on chromosomes.
Gene mapping
What is an example of linkage?
Two genes on a single pair of homologs; exchange occurs between two nonsister chromatids.
Gene mapping
What determines the likelihood of recombination?
The distance between genes determines the likelihood of recombination.
Two genes that are far apart have many chances of crossing over while two genes that are extremely close together do not have the possibility of crossing over due to strong linkage.
Gene mapping
What are genetic and physical markers?
A genetic marker is a DNA sequence, such as an SNP or repeat.
A physical marker is a phenotype associated with a gene locus.
Gene mapping
What is a test cross and what are they used to determine?
A test cross crosses an F1 heterozygote with a homozygous recessive tester. If we are interested in two genes, a two-point test cross is used.
Gene mapping
How do we know which progeny (offspring) are recombinant and which are parental?
Recombinant progeny have a different combination of markers from the parent, indicating a crossover has occurred.
Parental progeny have the same combination of markers as the parent.
Gene mapping
What do the results of a test cross indicate if:
50% recombination between e and vg genes
F2 phenotypic classes:
e vg : 25% parental
e vg+ : 25% recombinant
e+ vg : 25% recombinant
e+ vg+ : 25% parental
The genes are very far apart on the same chromosome, OR on different chromosomes indicating independent assortment.
Gene mapping
What do the results of a test cross indicate if:
No recombination between e and vg genes.
F2 phenotypic classes:
e vg : 50% parental
e vg+ : 0% recombinant
e+ vg : 0% recombinant
e+ vg+ : 50% parental
Genes are very close on the same chromosome and have complete linkage.
Gene mapping
What do the results of this experiment indicate? And how do we determine the distance between the e and vg genes?
F2 phenotypic classes:
e vg : 1418 flies : 43.8% parental
e vg+ : 241 flies : 7.4% recombinant
e+ vg : 283 flies : 8.7% recombinant
e+ vg+ : 1294 flies : 40.0% parental
The e and vg genes are linked.
We determine the distance between genes by dividing the number of recombinants by the total number of progeny and then multiplying by 100 to get the number of map units (mu) the genes are apart.
((241 + 283) / 3236) * 100 = 16.2 mu
Genes e and vg are 16.2 map units apart.
Gene mapping
What happens during a double-crossover (DCO)?
A double crossover occurs when two chiasmata form and there is a double exchange between two nonsister chromatids.
Gene mapping
True or False:
Double-crossovers occur far less than single-crossovers.
True
Gene mapping
How do we know which progeny are parental, single-crossover, or double-crossover in a three-point cross?
Progeny in the lowest abundance are double-crossover recombinants.
Progeny in the highest abundance are parental.
Progeny in the intermediate range of abundance are single-crossover recombinants.
Gene mapping
What four steps will help in the determination of a three-test cross?
1) Determine the order of the genes
2) Reorganize the data to reflect the gene order
3) Calculate map units for the first two genes
4) Calculate map units for the second two genes
Gene mapping
Identify parental, region 1 SCO recombinants, region 2 SCO recombinants, DCO recombinants, gene order, recombination frequency, and map unit distance from the following data:
p+ j+ r+ 179
p j r 173
p+ j r 52
p j+ r+ 46
p+ j+ r 22
p j r+ 22
p+ j r+ 4
p j+ r 2
Total: 500
Parental:
p+ j+ r+ 179
p j r 173
SCO region 1:
p+ j r 52
p j+ r+ 46
SCO region 2:
p+ j+ r 22
p j r+ 22
DCO:
p+ j r+ 4
p j+ r 2
Gene order: pjr or rjp
DIstance p to j (region 1)
(SCO region 1 + DCO) / Total Progeny * 100
=20.8 mu
Distance j to r (region 2)
(SCO region 2 + DCO) / Total Progeny * 100
=10 mu
Distance p to r (region 1 + region 2)
20.8 mu + 10 mu = 30.8 mu
Gene mapping
In the progeny of a two-point test cross, what percentage of recombinant phenotypes is expected if the genes under study are independently assorting?
50%
Gene mapping
Two tomato plant genes A and B are linked and 40 mu apart.* A tomato plant homozygous at the A and B loci (AABB) is crossed with an ab plant (aabb). The resulting F1 generation is two-point testcrossed back to an ab tester (aabb). What percent of the progeny is expected to be Ab?
number of mu = % recombinants
40 mu = 40 % recombinants
20 % Ab and 20 % aB
Gene mapping
Three genes on the Drosophila X chromosome are examined pairwise. It is determined that they have the following recombination rates:
yellow, white 0.5%
white, miniature 34.5%
yellow, miniature 35.4%
Which two genes are physically closest together?
Yellow and white are physically closest together because 0.5% recombination translates to 0.5 map units between the genes compared to the other genes being 34.5 mu and 35.4 mu apart from each other.
Gene mapping
True or False:
Crossing over occurs at random.
False:
Chromosomes have recombination hot spots and cold spots.
Gene mapping
What causes a DCO recombinant to look like the parental phenotype?
The farther apart two genes are, the greater the probability that undetected DCOs will occur.
Gene mapping
What are some limits of mapping human genomes?
1) Unrealistic to use the same methods as model organisms
^Ethical considerations
^Long wait times (across generations)
^Low offspring number (low sample size)
2) Analyze multiple pedigrees using special algorithms
3) Analyze DNA markers (SNPs, microsatellites, etc.) from saliva samples using DNA arrays and genome sequencing
^Direct-to-consumer genotyping services like 23andMe are producing in population genetics data
Sex linkage
What are the two sex determination systems?
1) Genotypic sex determination
-due to specific DNA sequences
2) Environmental sex determination
-signals from environment
Sex linkage
What is genotypic sex determination and what are the three subcategories?
Remember GeChMa
Genotypic sex determination is due to specific DNA sequences.
The three subcategories are:
1) Genic balance
2) Chromosome determination
3) Mating-type determination
Sex linkage
What is Genic balance?
The ratio of sex chromosomes to autosomes controls the amount of sex-determining gene products
Sex linkage
What is Chromosome determination?
Chromosome determination is the presence or absence of gene product(s) encoded by sex chromosomes; or the presence or absence of a sex chromosome.
Sex linkage
What is Mating-type determination?
Mating-type determination is the expression of gene variants called idiomorphs, control mating type (in some haploid microbes).
(i.e. yeast can have MAYa and MAY(alpha) alleles.
Sex linkage
What is environmental sex determination? List examples.
Environmental sex determination is the signals from the environment.
(i.e. day length, temperature, social cues)
Sex linkage
List two examples of genic balance in organisms.
C. elegans : hermaphrodite-XX male-XO
Drosophila melanogaster: female-XX male-XY
Sex linkage
List two examples of chromosome determination in organisms.
Mus musculus (mice): female-XX male-XY
Xenopus laevis (frogs): female-ZW male-ZZ
Sex linkage
List an example of environmental sex determination in organisms.
Danio rerio (fish): female-None male-None
Sex linkage
What type of chromosomes determine biological sex?
A combination of heteromorphic sex chromosomes determine biological sex.
Sex linkage
The XX sex chromosome combination causes what biological features to develop?
The XX sec chromosomes cause the development of gonads into ovaries and produce eggs (a wild-type biological female).
Sex linkage
The XY sex chromosome combination causes what biological features to develop?
The XY chromosomes cause the gonads to develop into testes and produce sperm (a wild-type biological male).
Sex linkage
What are the different regions of a Y chromosome?
There are two main regions, one region includes SRY, euchromatin, centromere, and heterochromatin.
Pseudoautosomal region (PAR),
Male-specific region of the Y (MSY)
Sex linkage
What is the function of the PAR?
PAR synapses with the X chromosomes during meiosis.
Sex linkage
What is the function and sub parts of MSY?
MSY contains euchromatin which includes SRY, the sex-determining region of the Y chromosome.
Sex linkage
When is SRY expressed in development and what is its function?
SRY is expressed approximately 6-8 weeks after fertilization. SRY activates the SOX9 gene (testes development which secretes testosterone-shapes male sexual development). SRY represses WNT4 gene expression (controls expression of ovary development, which secrete estrogen-shapes female sexual development).
Sex linkage
Who and how was sex linkage discovered?
Sex linkage was discovered by Thomas Hunt Morgan through observing fruit flies.
Sex linkage
True or False
Many linked genes do not influence sex development
True
Sex linkage
True or False
Most sex-linked genes are Y-linked and not X-linked.
False:
Most sex-linked genes are X-linked because Y does not contain many genes.
Sex linkage
What are some examples of X-linked genes?
In humans: color perception, dystrophin (structure protein in muscles), blood clotting factors.
In cats: fur color pattern
In fruit flies: eye color
Sex linkage
Why are X-linked recessive inheritance traits more frequently observed in males in a family?
Males are hemizygous for genes on the X chromosome and have no second allele (i.e. XX in females) to compensate for the recessive allele.
Sex linkage
When do females with X-linked recessive inheritance alleles express the trait?
Females only express X-linked recessive inheritance traits when they are homozygous for the recessive allele.
*Females with only one recessive allele are carriers
Sex linkage
What are Barr bodies and what is their function?
Barr bodies are inactive X chromosomes that were deactivated during the blastocyst stage in XX mammals.
Sex linkage
What are two forms of imprinting regarding Barr bodies?
1) Monoalleleic expression allows for gene dosage compensation
2) Equal amounts of X-linked gene expression between males and females
Sex linkage
True or False
A Barr body is formed through lyonization
True
Sex linkage
What gene is involved with Barr bodies?
Involves XIST gene on the X chromosome and is weakly expressed from both X chromosomes.
Sex linkage
What occurs to the XIST gene and what does it do?
During early development, one XIST gene copy is silenced and becomes the active X chromosome while the other active XIST gene causes that X chromosome to become a Barr body.
XIST encodes a long non-coding RNA (lncRNA) using DNA methyltransferases and HDAC to pack up the chromosome.
Sex linkage
What is mosaicism?
Mosaicism is a mixed phenotype resulting from different genotypes or gene expression levels in the cells of a multicellular organism.
Sex linkage
Can random Barr body lyonization cause monoallelic expression?
Yes, Barr bodies can cause monoallelic expression in different cells of the body as well as some cells either having the paternally or maternally derived X chromosome silenced and only express maternally or paternally derived X chromosome genes, respectively.
Sex linkage
True or False
All mitotic descendants of a cell inherit the parent cell’s inactivation pattern.
True
Sex linkage
What is an example of Mosaicism?
In cats, mosaicism is observed as multiple coat colors. Coat color locus on the X chromosome codes for orange and black alleles. Some cells with X chromosome express the black fur pigment allele, while others express orange fur pigment allele.
Sex linkage
What are some cytogenetic observations that supported a Y chromosome sex determination mechanism in humans?
Aneuploid conditions:
1) 45, XO (Turner syndrome) are phenotypically female w/ ovaries
2) 47, XXY (Klinefelter syndrome) are phenotypically male w/ testes
Sex reversal conditions:
1) 46, XY females with deletion of the Y chromosome
2) 46, XX males had a small piece of Y attached to X (most likely the SRY region)
Sex linkage
What are three types of sex-linked disorders in humans?
1) X-linked recessive: Human color blindness
-Loss of function mutations in genes encoding photoreceptor proteins in the eye located on the X chromosome cause color blindness
2) X-linked dominant: Rett syndrome
-Type of autism caused by the missence or nonsense mutations in gene encoding methyl-CpG-binding protein 2.
-This gene must function properly in order for maturation of neurons.
3) Y-linked (holandric traits)
-Very few identified
Sex linkage
Questions about X-linked recessive inheritance:
1) What proportion of the sons of an affected XX mother would show the trait?
2) What proportion of the sons of a carrier XX mother would show the trait?
3) What proportion of XX daughters would show the trait from an unaffected XX mother and affected XY father?
4) What proportion of XX daughters would show the trait from an affected XX mother and unaffected XY father?
3) Assume “unaffected XX mother” could be heterozygous for the trait or homozygous unaffected. Solve for both.
1) 100% of sons would show the trait
2) 50% of sons would show the trait
3) 0% if homozygous, 25% of daughters affected if heterozygous for the trait.
4) 0% of daughters affected
Sex linkage
What does hemizygous mean and how is it related to XY humans?
Hemizygous means an individual who has one member of a homologous pair of chromosomes rather than two. Males are hemizygous for the gene on the X chromosome.
Sex linkage
Questions about X-linked dominant inheritance:
1) If the XX mother is heterozygous and XY father is unaffected, what proportion of their XY sons will be affected? XX daughters?
2) If the XX mother is unaffected but the XY father is affected, what proportion of their XX daughters will be affected? XY sons?
1) 50% XY sons affected, 50% XX daughters affected
2) 100% XX daughters affected, 0% XY sons affected
Sex linkage
How does the determination of the sex of the fly (D. melanogaster) differ from human sex determination?
The ratio of the number of X chromosomes to sets of autosomes determine the sex of the fly.
Extensions of Mendel
How many alleles can a single diploid have for a given genes?
A single diploid can only have up to 2 alleles for a given gene.
Mutations can lead to more than 2 alleles.
Extensions of Mendel
How is the number of possible genotypes in a population calculated?
Possible genotypes = n(n+1)/2
n= number of alleles
(i.e. If there are 4 possible alleles, the number of genotypes in the population is 4(4+1)/2 = 10)
Extensions of Mendel
What is codominance?
Codominance is when heterozygotes simultaneously show the phenotypes that would be seen in the homozygotes.
(i.e. a cow heterozygous for white and red hair = white and red hair both shown in the cow, no blending of colors)
(i.e. Blood type, AB, both alleles are expressed)
Extensions of Mendel
Explain codominance on a molecular level?
Three answers
1) Equal amounts of gene product from both alleles
2) Both alleles are expressed and have equal activities
3) Gene products do not interfere with each other
Extensions of Mendel
What is incomplete dominance?
Incomplete dominance is when one allele is not completely dominant to the other allele. A third, blended phenotype is presnt in the population.
(i.e. palomino horses: Chesnut (dark brown), Palomino (medium brown), Cremello (light brown))
Extensions of Mendel
What is the molecular explanation of incomplete dominance?
2 answers, one has 3 subfields
1) Varies from trait to trait
2) Can be dependent on gene dosage
-Homozygosity for functional allele causes two doses of the gene product
i.e. red snap dragon
-Heterozygosity causes one dose
i.e. pink snap dragon
-Homozygosity for the null allele no dose
i.e. white snap dragon
Extensions of Mendel
What is pleiotrophy?
Pleiotrophy is when one gene is responsible for multiple traits.
(i.e. phenylketonuria (PKU): PAH gene product involved in metabolizing phenylalanine; PKU caused by homozygosity or compound heterozygosity (having 2 different mutant alleles) for loss-of-function pah alleles, so that phenylalanine accumulates in cells; lower IQ, seizures, light skin pigmentation result)
Extensions of Mendel
What is pleiotrophy on a molecular level?
2 answers
1) Promiscuous protein has more than one function
2) Cell-specific effects of protein variants
-(i.e. neurons are more sensitive to loss of PAH function than other cells types)
Extensions of Mendel
What is an essential gene?
An essential gene is a gene product required for life of a cell or organism.
-No compensating gene or gene with redundant function to take its place
-When the function of the gene product is mutated, a lethal allele results
Extensions of Mendel
What is a lethal allele?
A lethal allele causes the death of the organism.
-aka. deleterious allele
-Different than a null allele, although a lethal allele can also be a null allele
Extensions of Mendel
What are polygenic traits?
Polygenic traits are multiple genes that contribute to a trait.
Extensions of Mendel
What is epistasis?
Epistasis refers to when two genes are involved, and one gene interferes with the expression of the other gene.
The epistatic gene suppresses the phenotype from the hypostatic gene.
Extensions of Mendel
What are complete recessive alleles?
Complete recessive alleles are often null alleles due to loss-of-function mutation.
(i.e. wrinkled pea vs round pea)
Extensions of Mendel
What are complete dominant alleles?
1) Gain of function: amount of gene product activity is wild type or increased
2) Loss of function: null allele
-Dominant negative mutant
-Haploinsufficiency
Extensions of Mendel
What is a dominant negative mutant?
A dominant negative mutant is a mutant gene product that interferes with the wild-type gene product.
Extensions of Mendel
What is haploinsufficiency?
In haploinsufficiency, heterozygosity reduces the amount of gene product so that the wild-type phenotype cannot occur.
Extensions of Mendel
Traits like familial hypercholesterolemia follow incomplete dominance are actually considered dominant. Why?
Phenotype is still visible in heterozygotes, even though it is to a lesser extent.
