Genetics Exam 3

A region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes

Telomere structure

Constricted region of a chromosome where spindle fibers attach, surrounded by heterochromatin, essential for chromosome separation

Centromere structure

A telomere is a region of ______nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. DNA at the ends of eukaryotic chromosomes consists of telomeric short repeated sequences.

repetitive

The G-rich strand at the telomere is longer than the ___ ___ strand.

C-rich

In mammalian cells, the G-rich strand folds over and pairs with a short stretch of DNA to form a ____ ___

t-loop

Telomere length is inversely proportional to blood lead level in children. Shorter relative telomere length in peripheral blood is a risk marker for some types of _____ ____ ____ ____

cancers and cardiovascular diseases.

the region of a chromosome to which the microtubules of the spindle attach, via the kinetochore, during cell division.

Centromere

a complex of proteins associated with the centromere of a chromosome, to which the microtubules of the spindle attach during cell division.

Kinetochore

a small, cylindrical cell organelle, located near the nucleus in the cytoplasm of most eukaryotic cells, that divides in perpendicular fashion during mitosis

Centriole

The centromere is the chromosomal locus essential for chromosome inheritance and ____ ____

genome stability

The physical role of the centromere is to act as the site of assembly of the kinetochore - a highly complex multiprotein structure that is responsible for the actual events of ____ ____

chromosome segregation

What happens when a chromosome breaks producing a fragment without a centromere?

Fragment will be lost

___meters of DNA compressed into a 10 m nucleus

2

____ must be tightly packed to fit in small spaces

DNA

The enzyme responsible for adding and removing turns in the coil.

Topoisomerase

Supercoiled DNA is overwound or underwound, causing it to ____ on itself.

twist

Most bacterial genomes have a ____ circular DNA molecule that twists during condensation and is held in place by proteins

single

Chromatin structure

– Euchromatin – Heterochromatin – Histone proteins

Histones have a positive charge and DNA is ____ ____ – hence the attraction.

negatively charged

A basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound in sequence around eight core histone proteins.

The nucleosome

A histone octamer, one molecule of linker histone, (for example, Histone H1) and 166bp of DNA. The linker histone is a binding agent, acting like a finger holding down the DNA preventing its release.

Chromatosome

Chromatin has a highly ______ structure with several levels of organization.

complex

The nucleosome is the fundamental repeating unit of ____

chromatin.

What is less condensed, on chromosome arms, have unique sequences, many genes, throughout S phase, often in transcription, and crossing over is common?

Euchromatin

What is more condensed, at centromeres, telomeres, and other specific places, has repeated sequences, few genes, late S phase, infrequent transcription, and uncommon crossing over?

Heterochromatin

Chromosomal puffs are regions of relaxed chromatin where active transcription is taking place. (Chromosomes isolated from the salivary glands of larval drosophila)

Polytene chromosomes

DNase I sensitivity is correlated with the transcription of globin genes in ____ ____

chick embryos.

The procedure involves heating a sample of genomic DNA until it denatures into the single stranded-form, and then slowly cooling it, so the strands can pair back together. While the sample is cooling, measurements are taken of how much of the DNA is base paired at each temperature.

Repeated sequences anneal more quickly, Single-copy sequences anneal slower

Plays an important role in the assembly of heterochromatin and regulation of gene expression. These changes can be passed down to progeny and can be altered by the environment that the cells are subject to. Epigenetic alterations are reversible suggesting that they can be targets for therapy.

DNA and Histone methylation

Is a heritable alteration of phenotype because of altered chromatin structure (histone modification, acetylation) or the modification of DNA (methylation) without changing the DNA sequence

Epigenetics

These mice are genetically identical but have different levels of _____of the DNA at the agouti locus which controls coat color

methylation

These 2 mice are genetically identical and the same age. While pregnant their mothers were fed ____ ___

Bisphenol A (Plastic Hardener)

Folic acid is a ____ donor.

methyl

The differences in coat color are linked to differential methylation of gene regulating coat color and obesity. ___ ____ is a rich source of methyl groups

Folic acid

Each person has a unique “_______” of microsatellites - very useful in forensics

Fingerprint

Microsatellites, short tandem repeats (STRs), are often used in _____ analyses

Forensic

Sequences that can move about the genome

Transposable elements

movement of the transposons

Transposition

•Flanking direct repeats •Terminal inverted repeats

Features of Transposons

Transposable elements are mobile DNA sequences found in the genomes of all organisms. • Make up at least 45% of human DNA • Most are able to insert at many different locations. • Rely on mechanisms distinct from homologous recombination • Often cause mutations

Transposons

More_____ genomes have more transposons

complex

Short flanking repeats from 3 to 12 bp long are present on both sides of the transposable elements. • Do not travel with the transposable element • Regenerated at the point of insertion • Staggered cuts are made in the target DNA, leaving short, single-stranded pieces of DNA on either side of the transposable element. • Replication of single-stranded DNA creates the flanking direct repeats.

Common Features of Transposon

Transposons are terminal, _______ repeats (9 to 40 bps) are found at ends of many transposable elements

inverted

_____ direct repeats are generated when a transposable element inserts into DNA after a staggered cut.

Flanking

Transposable elements have common characteristics. Most transposable elements generate flanking direct repeats on each side of the point of insertion into target DNA. Many transposable elements also possess _____ inverted repeats

terminal

Transposons cause mutations by

Inserting into another gene, promoting DNA rearrangements

Approximately half of spontaneous mutations in Drosophila, human genetic diseases: Some genes are more susceptible to transposon integration, the color of grapes

Examples of Transposons causing mutation

Red and white fruit color in grapes results from insertion or deletion of a ______

retrotransposon.

Only DNA transposons are found in _____

bacteria

A bacterial insertion sequence has only enough information to _____ _____

facilitate moving

A bacterial composite transposon retains enough information to transpose. Tn10 carries the ______ resistance sequence

tetracycline

__ is a transposing bacteriophage.

Mu

• Staggered breaks are made in the target DNA • Transposable element is joined to single-stranded ends of the target DNA. • DNA is replicated at the single-strand gaps.

Common features in mechanisms of transposition

A new copy of the transposable element is introduced at a new site while the old copy remains at the original site. • Results in an increase in the number of copies of the transposable element. • Can be either between two different DNA molecules or between two parts of the same DNA molecule.

copy and paste transposons/replicative transposition

Single copy of the transposable element is on one DNA molecule • Two DNA molecules are joined • Transposable element is replicated • Results in the production of a cointegrate structure: • Two DNA molecules plus two copies of the transposable element • Crossing over at regions within the copies of the transposable element produces two molecules, each with a single copy of the transposable element = resolution of the cointegrate.

Events necessary for co-integrate formation

an enzyme that binds to the end of a transposon and catalyzes the movement • May be encoded by cellular gene or often by transposable element • Makes single-strand breaks at each end of the transposable element and on either side of the target sequence where insertion occurs

Transposase

An enzyme which brings about the separation of two transposons contained in a cointegrate during the process of replicative transposition • Encoded either by cellular genes or by transposable element • Responsible for resolution

Resolvase

Transposable element is excised from old site and inserted into a new site • Does not increase number of copies.

non-replicative transposition (cut and paste)

Similar to retroviruses • Include Ty elements in yeast, Copia elements in Drosophila, Alu elements in humans

Retrotransposons: (reverse transcribed)

These are elements that transpose through an RNA intermediate (in contrast to DNA transposons). • RNA is transcribed from a DNA transposable element. • RNA is copied back to another DNA site using reverse transcriptase. • Only done through replicative transposition • More common than DNA transposons in eukaryotes.

retrotransposons

Ty transposable element in yeast

example of retrotransposon

Chromosomal rearrangements are a consequence of _____ ____

transposed sequences

One of her ideas was the notion of genetic recombination by crossingover during meiosis. During the 1940s and 1950s, McClintock discovered transposition (transposons) and used it to demonstrate that genes are responsible for turning physical characteristics ___ ___ ___

on and off.

Barbara McClintock discovered ______ _____

transposable elements (TE)

Ac and Ds

are transposable elements in maize

Transposition results in_____ maize kernels.

variegated

The discovery of the first known active human L1 element was the result of its retrotransposition into the factor VIII gene, causing a de novo case of hemophilia

threw out of frame

These results indicate that LINE1 RNA and PRC2 maintain H3K27me3-mediated gene repression and 3D nuclear organization to prevent developmental reversion of hESCs. They help maintain methylation that result in progression of one embryonic stage to the next, developmental progression in the ____ human embryo

early

Transposons may have coordinated progesterone responsiveness that led to the evolution of pregnancy in mammals

common elements share ancient similarity at transposons

Transposons associated with ________diseases. ALS, a third group (20%) exhibits high levels of retrotransposon expression and signatures of TARDBP/TDP-43 dysfunction

neurodegenerative

____ is an important tumor suppressor.

p53

Emerging lines of evidence suggest that cancers driven by p53 mutations could represent ‘transposopathies’, i.e. disease states linked to eruptions of ____ ___

mobile elements

Use a transposon to clinically modify and target genes

The Sleeping Beauty Transposon System