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Differentiate Euploidy and Aneuploidy.

A euploid organism has multiples of the basic chromosome set (genome); ex. 2n, 3n, 4n

An aneuploid organism's chromosome number differs from the wild type by part of a chromosome set; ex. 2n + 1, 2n - 1


What are the three major types of chromosome mutations?

1) Relocation of genetic material, ie. translocation and inversion
2) Loss of genetic material, ie. deletion
3) Gain of genetic material, ie. duplication and extra chromosomes


Why are triploids most often sterile?

Due to unpaired chromosomes at meiosis, gametes will either receive one or two chromosomes for each chromosomal type. It is unlikely that they will receive the same number of each chromosome type, and so they are most often aneuploid, and inviable.


In what organisms is polyploidy common, and what are its effects?

Plants, as shown by much higher incidence of even numbers of chromosomes above haploid number 12, indicating doubling.

Polyploid plants are often larger than diploid plants, but remain proportional.


What is nondisjunction?

A failure of normal segregation of homologous chromosomes or chromatids during meiosis I or II; two chromosomes incorrectly go to one pole or the other.


What is the difference between primary and secondary nondisjunction?

Primary nondisjunction occurs in meiosis I (anaphase); products will be two O gametes, and two 2n gametes with different chromatids if parent is heterozygous.

Secondary nondisjunction occurs in meiosis II (anaphase); products will be one O gamete, one 2n gamete with the same chromatids, and two normal 1n gametes with the other chromatid.


Why does the chance of a child with Down's syndrome increase with maternal age?

Oocytes arrest in meiotic prophase I and resumes at each menstrual period; with age, the bivalents must stay together for longer and longer, and likelihood of mutagenesis events breaking the bivalent increases. This leads to increased primary nondisjunction.


Explain what is meant by a "gene-dosage effect" in regards to human aneuploidy.

In general, the amount of transcript produced by a gene is directly proportional to the number of copies of that gene in a cell. If there is an extra (or missing) chromosome, this leads to uneven gene dosage, interfering with gene function. Because of this, human aneuploidy is almost always lethal.


Which cases of human sex chromosome aneuploidy are fertile?

XYY and XXX are fertile and have no obvious phenotype.


What is the result of an XO genotype? What type of nondisjunction could lead to this genotype?

Turner syndrome - female with underdeveloped gonadal structures, sterile

Could occur due to primary or secondary nondisjunction in either parent.


What is the result of an XXY genotype? What type of nondisjunction could lead to this genotype?

Klinefelter syndrome - sterile male with underdeveloped gonadal structures, IQ impairment, and some breast development

Could occur due to primary nondisjunction in the father, or primary or secondary nondisjunction in the mother.


Can a single meiotic nondisjunction event give rise to both a Klinefelter child and a child with Turner syndrome?

If so, would it be a primary nondisjunction, a secondary nondisjunction, or is either possible?

Yes, it could. During a primary nondisjunction event.


What rules govern sex determination in drosophila?

One X chromosome --> male
Two X chromosomes --> female

absence of X is lethal, three X chromosomes is lethal


What rules govern sex determination in humans?

Y chromosome present --> male
Y chromosome absent --> female

absence of X is lethal


What are three funky ways in which sex can be determined in various species?

1) Bees and Wasps --> females are diploid, males are haploid
2) Lizards and Alligators --> females in cool temperature development, males in warm temperature development
3) Anemone --> young adult are male, older adults are female


A woman with Turner syndrome is also colorblind (an X-linked recessive phenotype). Both her parents have normal vision.

How is it possible for her to be colorblind if neither parent was?
Can you determine which parent experienced nondisjunction?
Did the nondisjunction event happen at meiosis I or II?

a) She only has one X chromosome, so whatever genotype it is is dominant. One of her parents must be a carrier.

b) Her mother must be the carrier, because her father would express the phenotype is he was. Thus, she must have received the X from her mother, and the O from her father.

c) Can't determine.


How do chromosomal inversions and translocations come about?

1) Double stranded breaks (x-ray zapping, etc.)
2) Crossing over between repetitive sequences in the genome (like those produced by transposable elements)


What is the difference between a paracentric and pericentric inversion?

Paracentric doesn't include the centromere, pericentric does.


What is the problem with dicentric and acentric fragments?

They either lack a centromere and won't be pulled to either pole in anaphase, or they have two centromeres and will be pulled to both poles simultaneously.


What does a chromosome require in order to replicate properly?

exactly 1 centromere, and 2 telomeres


Why is the inversion loop produced?

When chromosomes line up in meiosis, the inverted chromosome twists to properly pair with the same genes on the non-inverted strand, creating an inversion loop. Crossing over in an inversion loop yields acentric and dicentric fragments, as well as duplications and deletions.


Why is TM2 a bad gene to have?

It has multiple inversions, and is homozygous lethal; Gametes that are products of recombination are inviable, and heterozygotes carrying TM2 might be sicker than wildtype.


Describe the basic transcriptional regulation process in prokaryotes?

Activators and repressors bind to sites in the vicinity of the promoter to control accessibility of DNA to RNA polymerase.


What are the structural genes in the lac operon?

Z: ß-Galactosidase
Y: Permease
A: Transacetylase


What are the regulatory components of the lac operon?

I: the lac repressor protein encoding gene
P: the promoter that initiates the transcription of the structural genes
O: the lac operator site to which the lac repressor protein binds
crp: the CAP encoding gene


Describe the mechanism by which the presence of lactose in an environment allows for the synthesis of lactose processing proteins.

1) In presence of lactose, lactose functions as an inducer, and binds to an allosteric site on the repressor protein
2) Repressor protein can no longer bind to the operator sequence, and falls off
3) The RNA polymerase is then able to transcribe the lac structural genes.


What is meant by constitutive mutations?

Constitutive mutations cause the lac structural genes to be expressed regardless of environmental factors --> transcription is no longer inducible.


What is the effect of an I-/I+ phenotype?

I- mutations stop the transcription of the repressor protein, but the repressor is trans-acting, so the I+ will be the dominant phenotype, and transcription is still inducible.


What is the effect of an Is/I- phenotype?

Is mutations lead to production of repressors that cannot be bound by inducers. Thus, the Is repressors would bind both of the operator sequences, leading to the halt of all production of lac structural genes.


What is the effect of an O+/Oc phenotype?

The Oc mutation is cis-acting, meaning is only affects one strand. However, no repressor will be able to bind that operator sequence, so lac structural genes will always be transcribed at low levels, despite the other strand's operator sequence still functioning in the negative feedback loop.


How does the presence of glucose affect the operation of the lac operon?

In the presence of glucose, cAMP is present at very low levels. In the absence of glucose, cAMP is present at high levels, and can bind to CAP which then binds to a sequence in the lac operon, allowing transcription.


How would a crp- mutation affect transcription of lac structural genes?

A crp- mutation would halt synthesis of CAP. cAMP would not be able to bind CAP, even if it were present in high levels as in low-glucose conditions. The lac operon would be inducible but would only produce very low (basal) levels of proteins.


Describe the mechanism by which trp operon gene expression is governed by levels of tryptophan in the environment.

1) Simple negative feedback - trp repressor binds tryptophan when present in significant amounts, and then can bind operator sequence to switch off tryptophan production

2) Attenuation - post transcription; a leader sequence between the trp operator and the trpE gene is transcribed and translated; contains two trp codons, so if trp is abundant in the cell, enough trp tRNAs will be present for the ribosome to move past both codons quickly, leading to a formation of a step and loop in the mRNA that favors the halt of transcription. But, when trp is not present, the ribosome stalls at the trp codons, favoring the continuation of transcription.


How are transcriptional regulation in eukaryotes and prokaryotes the same?

Both utilize control of transcription through DNA binding proteins (ie. activators and repressors, transcription factors)


What mechanisms of transcriptional regulation differ between eukaryotes and prokaryotes?

Prokaryotes - operons, attenuation
Eukaryotes - chromatin structure, differential splicing, mRNA processing, differential polyadenylation, differential transport of nucleus to cytoplasm, RNA interface carried out by microRNAs


What is the large-scale functional difference between prokaryotic and eukaryotic transcriptional regulation?

Bacterial genes are "on" in the ground state, for the most part, while eukaryotic genes are "off." Eukaryotes require the presence of transcription factors and enhancers to initiate and continue transcription.


What are promoter-proximal elements?

Sequences (TATA, CAAT, GC-rich) found near the promoter that interact with TFs to allow the binding of RNA polymerase and the initiation of transcription; these alone will produce only basal levels of transcription.


What are enhancers/upstream activating sequences?

Cis-acting regulatory sequences that be located far away from promoters, but interact with TFs to make the environment more optimal for RNA polymerase, increasing transcription above basal levels.


Describe the mechanism by which Gal4 regulates genes through UASs.

Gal 4 is a sequence specific DNA binding protein (aka TF) that binds to many UASs. In the absence of galactose, the activation domain is bound by Gal 80. In presence of galactose, Gal80 undergoes a conformational change, and allows Gal 4 to enhance transcription of target genes.


What are the two domains of the Gal4 protein and what are their functions?

1) Activation domain - activates transcription
2) DNA-binding domain - binds to the correct DNA sequence


What is the structure of chromatin?

A nucleosome is composed of DNA wrapped around eight histones. Nucleosomes exist in coiled chains that are condensed to different degrees and make up chromatin fibers.


How do histones relate to transcriptional regulation?

Histones are heavily modified post-translation; protruding amino terminal ends (histone tails) can become acetylated or methylated through covalent bonding, influencing how tightly DNA is bound and packed.


How might a readily transcribable gene's chromatin structure differ from a non-transcribed gene's?

DNA methylation is associated with inactive genes and leads to closed chromatin.

Histone modifications, including acetylation and some methylation events, lead to open chromatin that can be transcribed more efficiently.


Differentiate heterochromatin from euchromatin.

Euchromatin is DNA actively in use and is acetylated; heterochromatin is inactive, DNA methylated.


How might histone modifications be inherited?

When the replisome copies the parental strands, it also disassembles the nucleosomes in the parental strands and reassembles them in both parental and daughter strands. Old histones provide a template for the modification of new histones to match.


What is gene imprinting?

A phenomenon in which certain autosomal genes are only expressed if they are inherited from either the mother or father. Maternal imprinting if gene from mother is inactive, vise versa.


How does imprinting work on a molecular level as in ifg2 and H19 in mice?

In females, the imprinting control region is unmethylated, and can bind to s CTCF dimer, forming an insulator that blocks enhancer activation of lgf2, such that only H19 is expressed.

In males, the imprinting control region is methylated, preventing binding of CTCF dimer, and also preventing transcription of H19, so only lgf2 is expressed via the action of the downstream enhancer.


What is a Barr body?

In females, the inactivated X chromosome that can be seen in the nucleus as a darkly staining, highly condensed, heterochromatic structure.


What is a model for the inactivation of one X-chromosome in females?

1) X-inactivation center locus (Xic) of X to be inactivated produces 17kb noncoding RNA Xist.
2) Xist binds Xi-coating protein, and transfers it to the DNA strand.


How might genetic silencing proceed?

Histone methylases bind to histone complex, and recruit DNA methylases, etc.


Why does Handel et al. suggest we need to rethink twin studies?

Previously, it has been assumed that discordance in twins is due to environmental factors. Now, we must also consider randomly and environmentally determined gene methylation patterns that diverge heavily as twins age.


What environmental factors might affect the epigenome?

Stress, smoking, sex hormones, and dramatically poor nutrition


What was the question and the main findings of Dolinoy et al?

Dolinoy et al. looked at the effect of maternal BPA exposure on variation in offspring coat color. They found that offspring coat color was lighter when mothers had been exposed to BPA, and this lightness of coat was associated with decreased methylation of CpG sites. Importantly, methylation in different tissue layers did not differ, indicating that the effect of BPA probably occurs very early in fetal development.


What are the basic requirements of evolution?

1) Must be genetic variation within a population
2) Variation must be heritable; individuals who reproduce effectively will contribute more to the genetic makeup of the population
3) Some alleles confer advantages in survival and reproduction, and some confer disadvantages


What forces tend to decrease variation in a population?

1) Directional selection
2) Genetic drift
3) Selection against heterozygotes


What forces tend to increase variation in a population?

1) Balanced polymorphism
2) Migration
3) Mutation


Why are large populations more genetically diverse than small populations?

In small populations, alleles are easily lost to genetic drift over generations, while in larger populations, the effects of genetic drift are minimized.


What is a selective sweep?

When one advantageous mutation is selected for, the genetic material around it is also selected for via recombination


How can neutral mutations be used to track how long ago two species diverged?

Neutral mutations accumulate steadily, and aren't selected for, or against. The number of different neutral mutations might be an indicator of how long ago two species began mutating separately.


What do differences in number of amino acid substitutions tell us about two species?

This tells us how quickly, and how much, a species is diverging; more neutral substitutions indicates more sensitivity to mutation, ie. quicker change. This is due to fewer highly conserved sequences that are essential to function.


What does the ratio of synonymous to nonsynonymous mutations in a gene tell you?

Whether the gene has undergone selection. If the number of nonsynonymous mutations is lower than synonymous, the gene has undergone purifying selection. If the ratio is equal to 1, the gene is probably not a functional gene (ie. fingerprints).


How do gene duplications come about?

1) transposons/retroviruses
2) nondisjunction events
3) small insertions from crossing over


What can happen to a duplicate gene?

1) Gene inactivation (pseudogenization)
2) Evolution of a new function (neofunctionalization)
3) Function of gene is divided between the duplicates (subfunctionalization)


What are some key features about the life cycle of HIV?

- a retrovirus with two copies of the RNA genome per particle
- has three open reading frames, with 3 genes coding for inner proteins, outer proteins, and replication proteins
- interacts with protein receptor on T-cells, virus fuses with cell, reverse transcriptase generates DNA from RNA and jumps into the genome --> many copies of the virus in the genome and translation of viral proteins


What are mechanisms by which HIV evolves at such a fast rate?

1) Fast replication rate with error prone reverse transcriptase --> more mutations, faster
2) Under selective pressure by immune system and drug therapies
3) Recombination between two RNA genomes per molecule, and between different strains present in one person