ch8 - variation in chromosome structure and number

cytogeneticists

scientists who study chromosomes microscopically

how are chromosomes classified?

according to centromere location

• metacentric

• submetacentric

• acrocentric

• telocentric

metacentric

centromere near the middle

submetacentric

centromere slightly off center

acrocentric

centromere significantly off center but not at end

telocentric

centromere at one end

chromosome arm structure

each chromosome has a short and long arm

• short arm = p (think petit)

• long arm = q

karyotype

photographic representation of all chromosomes within a cell

• chromosomes are aligned with short arms on top and long arms on bottom

how do you distinguish chromosomes from each other?

they are treated with dyes/stains that produce unique banding patterns for each chromosome

G-banding / Giemsa staining

chromosomes are exposed to Giemsa dye to produce unique banding patterns to distinguish the chromosomes

deletion

chromosome change where a segment of DNA is removed (so the chromosome is deficient in a portion of genetic material)

duplication / insertion

chromosome change where a segment of DNA is repeated more than once

when do deletions occur

when chromosome breaks or a fragment of chromosome is lost

what happens to the piece with the centromere and without the centromere during deletion?

• during deletion, the piece without the centromere is lost from future daughter cells because it doesn’t find its way to the nucleus during mitosis, and is degraded in the cytosol

• the piece with the centromere remains

terminal deletion

deletion where a segment is lost from the end of a linear chromosome

interstitial deletion

deletion where an internal segment is lost from a linear chromosome

how do duplications occur?

typically, crossover happens when homologous chromosomes align, but if crossover happens when homologs are misaligns, then a chromosome may carry two or more homologous segments of DNA that have identical or similar sequences

repetitive sequences

DNA sequences that occur many times in a genome

do duplications have phenotypic effect?

most chromosomal duplications have no phenotypic effect, but can lead to a gene family after many generations

gene family

two or more genes within a species that are similar to each other because they were derived from the same ancestral gene

paralogs

homologous genes within a single species

do duplications have phenotypic effect?

phenotypic consequences depends on:

• size of deletion

• chromosomal material deletion

more important gene deleted = phenotypic effect

how do duplications create gene families?

• Essential genes are critical for organism survival.

• Gene duplication creates a redundant copy- one maintains the essential function, the other is able to evolve.

• This forms gene families

copy number variation (CNV)

structural variation where a DNA segment that is at least 1000bp commonly has copy number differences among members of the same species

• AKA: CNV happens at the population level

how do you identify deletions and duplications?

microscopic methods and molecular techniques

what are the microscopic techniques to identify deletions and duplications?

• karyotyping

• fluorescence in situ hybridization

• comparative genomic hybridization (CGH)

karyotyping

• a microscopic method to identify deletions and duplications

• can be used to detect indels on a genome-wide level

fluorescence in situ hybridization

• a microscopic method to identify deletions and duplications

• one or more fluorescently labeled probes are hybridized to intact chromosomes, can be used to detect indels involving one gene or multiple genes

comparative genomic hybridization (CGH)

• a microscopic method to identify deletions and duplications

• fluorescently labeled probes from two different cells types (ex: noncancerous cells and cancer cells) are hybridized to an intact set of chromosomes. can be used to detect indels on a genome-wide level

what are the molecular techniques to identify deletions and duplications?

• DNA sequencing

• RNA sequencing

• polymerase chain reaction (PCR)

• array comparative genomic hybridization (aCGH)

DNA sequencing

• a molecular method to identify deletions and duplications

• the base sequences of DNA fragments are determined. can be used to detect indels in 1 gene or a group of genes

RNA sequencing

• a molecular method to identify deletions and duplications

• RNA is isolated from a sample of cells, and used as a template to create DNA for DNA sequencing. can be used to detect indels on a genome-wide level

polymerase chain reaction (PCR)

• a molecular method to identify deletions and duplications

• oligonucleotide primers are used to amplify a specific segment of DNA in a genome. can be used to detect indels involving one gene or multiple genes

array comparative genomic hybridization (aCGH)

• a molecular method to identify deletions and duplications

• fluorescently labeled probes from different cells types are hybridized to a DNA microarray. can be used to identify indels on a genome-wide level

indels

insertions and deletions

chromosome with an inversion

chromosome contains a flipped segment (so it runs in the opposite direction)

when do inversions occur?

when chromosome breaks at two sites and internal segment flips and reconnects in the opposite direction

pericentric inersion

centromere is located within inverted region of chromosome

paracentric inversion

• centrosome is located outside inverted region of chromosome

• think paranormal, “outside the norm” bc ghosts = outside the centromere

do inversions alter the phenotype?

inversions can alter the phenotype of an individual (rare cases) due to position effects or disruption of a gene or the formation of a new gene

break point effect

an inversion break point occurs within a vital gene, therefore separating it into 2 nonfunctional parts

position effect

gene is repositioned to alter gene expression

telomeres

• end of eukaryotic chromosome - repeated sequences of DNA to prevent translocations from occurring in eukaryotic chromosomes

• telomeres allow cells to identify where the chromosome ends and prevent the attachment of chromosomal DNA to the natural ends of a chromosome

simple translocation

part of one chromosome fuses with another chromosome

reciprocal translocation

two non-homologous chromosomes exchange genetic material

• also called balanced translocations since there’s no change in the amount of DNA

robertsonian translocation

abnormal chromosome for familial Down syndrome

• happens when two nonhomologous (not the same) acrocentric (centromere close to the end) chromosomes break near their centromeres

• then, the long arms of the two chromosomes fuse together, and the short arms are lost, creating one large chromosome

• for down syndrome, long arms from chromosomes 14 + 21 fuse, leading to extra chromosome 21 material, leading to down syndrome

when does variation in chromosome number occur?

occurs if there’s a change in the number of chromosomes within a set, or number of sets of chromosomes

euploid

organisms where the chromosome number is an exact multiple of a chromosome set

• AKA: same number of each type of chromosome (other than sex chromosomes)

how do you know if an organism is euploid?

divide total number of chromosomes by the number in a set. if whole number, then euploid

triploid

3n - organism with three sets of chromosomes

aneuploid

• not euploid

• total number of chromosomes is not a multiple of a set

what does “n” stand for?

the number of chromosomes in a set

aneuploidy

having too many or too few chromosomes - typically results in derimental phenotypes

why does the number of chromosomes matter?

the number of gene copies affects how much product is made

• more copies = more product

• fewer. copies = less product

trisomy

3 copies of a chromosome in a diploid cell

• one chromosome has 3 copies instead of 2, so genes on that chromosome produce ~150% of the normal amount, while other chromosomes product 100% → imbalance → aneuploidy

monosomy

1 copy of a chromosome in a diploid cell

• one chromosome has 1 copy instead of 2, so genes on that chromosome produce ~50% of the normal amount, while other chromosomes product 100% → imbalance → aneuploidy

autosomal human disorders to know

patau - trisomy 13

Edward - trisomy 18

down - trisomy 21

sex chromosomal human disorders to know

Klinefelter - XXY - phenotypically male, one Barr body

Jacobs - XYY

Triple X - XXX

Turner - XO - phenotypically female, no Barr body

is variation in X chromosomes lethal or nonlethal?

nonlethal because X-chromosome inactivation prevents overexpression

• inactive X-chromosomes = Barr bodies

nondisjunction

chromosomes don’t segregate properly during mitosis/meiosis - commonly leads to down syndrome

relationship between maternal age and down syndrome

• may be due to age of oocytes (produced in female fetus prior to birth and remain in prophase I until ovulation)

• older female = oocytes have been in prophase for a longer time, which may increase frequency of nondisjunction

meiotic nondisjunction

improper separation of chromosomes during meiosis

end result of meiotic nondisjunction

• haploid cells that have too many or too few chromosomes

• abnormal chromosome number in all cells

mitotic nondisjunction

• sister chromosomes don’t segregate properly during mitosis

• occurs after fertilization of a somatic cell

end result of mitotic nondisjunction

• one daughter cell recieves three copies of a chromosome, while the other daughter cell gets only one

• produces: a trisomic and monosomic daughter cell

when does nondisjunction occur?

during anaphase of meiosis I or II

nondisjunction during meiosis I

an entire bivalent migrates to one pole, net result is four abnormal cells

nondisjunction during meiosis II

net result is two abnormal and two normal haploid cells