genetics ch. 10 flashcards

what are chromosomes confined to

chromosome territories

chromosomes anchored by centromeres to territories

larger/more gene-rich chromosomes located in center of nucleus, smaller chromosomes with fewer genes located near periphery

have interchromosome domains between territories

what happens in interchromosome domains

channels for movement for proteins, enzymes, and large RNA molecules

what do karyotypes allow for

recognition of abnormalities in chromosome number or structure

autosomes numbered 1-22 from largest to smallest

what is in situ hybridization

uses molecular probes (DNA/RNA sequences) labelled with fluorescence to detect target sequences (like 32P)

currently use many fluorescently colored labels to identify with different wavelengths, all simultaneously (example - FISH, fluorescent in situ hybridization)

“in situ” = in place

describe a metacbntric chromosome shape

centromere is near middle of chromosome

describe a submetacentric chromosome shape

centromere is between the center and the tip

describe an acrocentric chromosome shape

centromere is very close to one end

describe a telocentric chromosome shape

centromere is at the tip of the chromosome and there is no p arm

describe an acentric chromosome shape

a piece of DNA without a centromere

what notation is used for the short and long arms of chromosomes

p - short arm

q - long arm

describe heterochromatin

more condensed

silenced genes (methylated)

more repetitive

stains darker

describe euchromatin

less condensed

actively expressing genes (acetylated)

less repetitive DNA

stains lighter

what is chromosome banding

allows cytogeneticists to identify each chromosome in a karyotypes by using stains and dyes

human chromosome banding - Giesma (G) banding

• 11 genes/band

• light bands - euchromatin

• dark bands - heterochromatin

• numbering begins at centromere

define aneuploidy

abnormalities in chromosome number

mitotic nondisjunction

if at first division, all cells become aneuploids

if later in development, there will be aneuploid sectors in an organism

meiotic nondisjunction

result of nondisjunction in gremlin cells is aneuploid gametes that can produce aneuploid zygotes

results in mosaicism

nondisjunction in meiosis 1

results from failure of homologous chromosomes to separate

fusion of these gametes with normal gametes produce trisomic or monosomic offspring

cannot produce any normal gametes

worse than meiosis 2 nondis.

nondisjunction in meiosis 2

failure of sister chromatids to separate normally

produces two normal games, one n+1 gamete (trisomic), and one n-1 gamete (monosomic)

effects of changes of gene dosage

causes an imalance of gene products from the affected chromosome

aneuploidy alters dosage of all the genes

• 50% more in trisomics, 50% less in monosomic

animals highly sensitive to gene dosage, plants not so much. humans are extremely sensitive to gene dosage

trisomy 13

patau syndrome

trisomy 18

edward syndrome

XXY

klinefelter syndrome (male)

XYY

Jacob syndrome (male)

XXX

triple X syndrome (female)

X0

turner sundrome (female)

human trisomy vs monosomy

trisomy can be seen, monosomeies are not observed because they do not survive

pallister-killian syndrome

presence of an extra isochromosome 12p, short arm of chromosome 12

loss of one arm, duplication of the other - a mirror image chromosome of 12p

tetrasomy of 12p

is a mosaic condition (not all cells have it)

trisomy 21

down syndrome

linked to advanced maternal age - over 35 - due to decrease in egg quality

mainly cognitive disabilities and heart abnormalities

caused by region on chromosome called DSCR - down syndrome critical region

candidate gene DYRK

describe Turner syndrome

monosomy of the X chromosome

phenotypically sterile

single copy of gene SHOX is haploinsufficient to direct normal development

can be mosaic with some XX, some XO, and some XXX

what causes mosaicism

mitotic nondisjunction in early embryogenesis

what is uniparental disomy

both copies of a homologous chromosome arise from the same parent

normal cells get one copy from mom and one copy from dad, uniparental disomy has both from mom or both from dad

how does uniparental disomy occur

normal gamete unites with a gamete with an extra chromosome copy, forming a trisomic zygote

trisomy rescue - one copy of the trisomy is randomly ejected at the beginning of mitosis after fertilization

2/3 chance normal, 1/3 chance it ejects the wrong one and end up with both copies from one parent

polyploidy

presence of three or more WHOLE sets of chromosomes

can occur through autopolyploidy or all-polyploidy

common in plants - makes fruits bigger

allopolyploidy

multiple sets of chromosomes that originate in DIFFERENT SPECIES

result in INTERSPECIFIC hybrid offspring that is infertile (chromosome sets are non homologous)

can become fertile if all chromosomes are doubled & nondisjunction occurs which allows pairing of homologs

can occur naturally or by human manipulation

• increase flower and fruit size, fertility is decreased

• hybrid vigor = more rapid growth

• disease resistance

bread wheat allopolyploid

triticum aestivum

hexaploid

from three separate varieties

amphidiploid

an interspecific hybrid having a complete diploid chromosome set from each parent form

also called allotetraploid (allopolyploid)

G. Karpechenko made a plant with the leaves of a radish and the roots of a cabbage

types of chromosome structure mutations

deletion, duplication, inversion, reciprocal translocation

terminal chromosome deletion

deletion of the end of a chromosome, containing genetic material and telomere

what is the name of the location where DNA strands are severed

chromosome break point

what happens to acentric chromosome fragments

they are lost during cell division because they can’t attach to the spindle apparatus

partial (terminal) deletion heterozygotes

organisms with one normal and one terminally deleted chromosome

example: cri-du-chat syndrome

interstitial deletion

loss of an internal portion of a chromosome

results from two chromosome breaks

example: WAGR syndrome is caused by deletion of multiple genes on chromosome 11

unequal crossover of homologs

causes partial duplication in one homolog and a partial deletion on the other

causes problems in gene dosage

• organism with one normal and one duplication = partial duplication heterozygote

• organism with one normal and one deletion = partial deletion heterozygote

unequal crossover isn’t common. commonly occurs when repetitive regions o homologs misalign (Williams-Beuren syndrome)

what do multigenic deletions cause

large duplication or deletion causes an area of mismatch - an unpaired loop when homologs pair

large duplications/deletions can be detected by FISH - detect presence or absence of particular DNA sequences

• microdeletions/microduplications are too small to detect by FISH

chromosome translocation

fragment reattaches to a non homologous chromosome

paracentric inversion

centromere not involved in the inversion

crossover within a paracentric inversion results in a…

• two abnormal chromosomes

  • dicentric chromosome

  • acentric fragment

• two normal chromosomes (with the inversion) - non crossover

dicentric chromosome will break at a random point because it is pulled by both centromeres during division

acentric fragment is lost because it lacks a centromere and is not attached to a spindle

pericentric inversion

centromere is within the inverted segment

crossover that occurs within a pericentric inversion results in…

• duplicated and deleted regions in both of the recombinant products (two abnormal gametes)

• two normal gametes (with an inversion) - non crossover

nonreciprocal translocation

unbalanced one way transfer

piece of one chromosome is translocated to a non-homolog, no reciprocal event

reciprocal balanced translocations

pieces of two non-homologs switch places

two way transfer

none of the four chromosomes have a fully homologous partner

tetravalent complex can split in three ways - two are bad and one is okay

• translocation heterozygotes are semi-sterile

robertsonian translocations

chromosome fusion - fusion of two non-homologs

reduces total chromosome number

fusion of chromosome 21 and (usually) 14 causes familial Down syndrome

• trivalent complex of one copy of 14 and one 14/21 fusion added to a normal parent with two copies of 21

what is the importance of chromatin

chromatin organization is essential to proper function & distribution of chromosomes during cell division

plays an important role in regulation of gene expression in eukaryotes

chromatin = DNA + associated proteins

composition of chromatin

half DNA half protein

half of the proteins are histone proteins, other has are non-histone proteins

what are the five major histone proteins

H1 - stabilization

H2A, H2B, H3, H4 (x2) = forms the octomer/nucleosome core particle

what is in a nucleosome

~146 bp long core DNA wrapped around an octomer

1º order structure of chromatin

the nucleosome - assembly of histones & DNA

1. H2A and H2B assemble into dimers

2. H3 and H4 assemble into dimers

3. two H3/H4 dimers form a tetramer

4. two H2A/H2B dimers associate with H3/H4 tetramer to form the octamer

DNA wraps around the octamer

what is the first level of DNA condensation

wrapping of DNA around the nucleosome

compacts DNA 7x

what is “linker” DNA

the DNA in between the stretched out nucleosomes,

string part of “beads on a string” - 10nm fiber (not observed under normal cellular conditions)

length of linker DNA varies among species. 200bp for linker + nucleosome in humans

2º order structure of chromatin

solenoid & 30nm fiber (observed naturally, not 10nm)

forms by 10nm fiber coiling into a solenoid structure

• 6-8 nucleosomes per turn

• H1 histone stabilizes the solenoid

higher order chromatin structure

occurs during metaphase of mitosis - condensation

forms a 300nm fiber

shape of chromosomes depends of the shape of the scaffold proteins

chromatin loops are anchored to scaffold proteins (non histone proteins) at sites called MARs (matrix attachment regions)

chromosome compaction allows for…

efficient separation of chromosomes at anaphase

link between condensation and gene expression

loops of chromatin formed during condensation play a role in regulation of gene expression

• high level of transcription in parts of loops farther away from the MARs (farther from the scaffold proteins)

• DNA near the MARs are less accessible & less expressed - less transcription

describe the nature of nucleosomes after DNA replication

contain some OLD and some NEW histone proteins

old histones may have epigenetic marks - methyl/acetyl groups

H3-H4 tetramers reassociate randomly with one of the sister chromatids; H2A-H2B dimers disassemble and reassemble from both old and new histones

what happens to histones during replication

nucleosomes must break down into component parts and release the DNA so it can pass through the replication fork

need to make lots more histone proteins for replication to occur, because twice as much DNA means it needs twice as many nucleosomes

synthesis and recycling during cell division

synthesize more histones, but also use old histones for the new replicated DNA