Chapter 10 - Eukaryotic Chromosome Abnormalities and Molecular Organization

What is a chromosome territory?

region within an interphase nucleus occupied by a particular chromosome during interphase; does not move from this position until M phase

What are interchromosomal domains?

open spaces between chromosome domains in the interphase nucleus; used for movement of proteins, enzymes, and RNA molecules

Describe the distribution of chromosome territories?

largest and most gene-rich chromosomes toward the center of the nucleus; territories of smaller chromosomes containing fewer genes are located toward the outer edges of the nucleus

What is a karyotype?

digital or analog photograph of chromosomes arranged by conventional chromosome numbering

What are chromosome arms?

segments of eukaryotic chromosomes between centromere and telomeres

What is the q arm?

long arm of chromosome

What is the p arm?

short arm of centromere

What is a metacentric chromosome?

chromosome with a centrally located centromere that produces long and short arms of approximately the same length

What is a submetacentric chromosome?

chromosome with a centromere located near the midpoint that produces long and short arms of different lengths

What is an acrocentric chromosome?

centromere is very near one end; short ends are called satellites because they are made of highly repetitive DNA

What are telocentric chromosomes?

chromosome with a centromere located at one end, producing a long arm only

What is fluorescent in situ hybridization?

laboratory method for identifying genes of DNA sequences using molecular probes labeled with a compound that can emit fluorescent light upon excitation

What is chromosome banding?

lab method to stain bands on chromosomes

What is Giemsa (G) Banding?

common type of chromosome banding

What is euchromatin?

chromosome regions containing chromatin that is not densely compacted; area of most expressed genes; light stained regions of G-banded chromosomes

What is heterochromatin?

chromosome region containing densely compacted chromatin; few expressed genes; dark stained regions

What is nondisjunction?

failure of homolog or sister chromatid separation during cell division; results in nuclei with wrong number of chromosomes

What does euploid mean?

number of chromosomes that is an exact multiple of the haploid number (n, 2n, 3n, etc)

What is aneuploidy?

uneven number of chromosomes; trisomy or monosomy

If nondisjunction occurs in Meiosis I, what are the gametes?

four are anuepolid - n+1 or n-1

What does trisomic mean?

three copies of a chromosome rather than a homologous pair of chromosomes and resulting in a number of chromosomes that is 2n+1

What does monosomic mean?

presence of a single chromosome instead of a homologous pair, resulting in a chromosome number that is 2n-1

What happens when nondisjunction occurs in meiosis II?

two cells will be normal; one will be monosomic and one will be trisomic

What is gene dosage?

number of copies of a gene in the genome

What effect does aneuploidy have on gene dosage?

monosomic mutant has one gene copy and 50% of normal gene dosage; trisomic has three copes and 150% of normal gene dosage

What is trisomy 13?

Patau syndrome; mental retardation and developmental delay, possible deafness, major organ abnormalities, early death

What is trisomy 18?

Edward’s syndrome; mental retardation and developmental delay, skull and face abnormalities, early death

What is trisomy 21?

Down’s syndrome; mental retardation and developmental delay, characteristic facial abnormalities, short stature, variable life span

What is XXY?

Klinefelter’s syndrome (males); variable secondary sexual characteristics, infertility, frequent breast swelling

What is XYY?

Jacob’s syndrome (males); tall stature, possible reduction but not loss of fertility

What is XXX?

triple X syndrome (females); tall stature, possible reduction of fertility, menstrual irregularity

What is DSCR?

Down syndrome critical region; portion of chromosome 21; when the additional fragment contains this region, symptoms of down syndrome are present

What is DYRK?

gene on DSCR that has a homolog that produces dosage-sensitive learning defects

What is SHOX?

pseudoautosomal region 2 on the short arm of X chromosome (and Y); haploinsufficiency of the gene may play role in Turners

What is mosaicism?

different cells of the organism contain differently functioning X chromosomes; can also develop as a consequence of mitotic nondisjunction early in embryogenesis

What is uniparental disomy?

presence of a pair of homologous chromosomes that originate from a single parent

What are the two mechanisms of origin for uniparental disomy?

nondisjuction of the same chromosome in sperm and egg and fertilization occurs in which one gamete contributes two copies of the chromosome and the other does not; nondisjunction in one parent that results in an aneuploid gamete contributing a normal gamete with a single copy of the chromosome

What is trisomy rescue?

random loss of one extra chromosome to reduct the chromosome number to the diploid

What is polyploidy?

presence of more than two complete sets of chromosomes

What is autopolyploids?

pattern of polyploidy produced by the duplication of chromosomes from a single genome

What is allopolyploids?

polyploid organism arising through the union of chromosome sets from different species

What are the two common mechanisms for polyploidy?

one or both gametes have an extra set of chromosomes that is contributed at fertilization (meiotic nondisjunction); doubling of chromosome number from mitotic nondisjunction; can also combine both mechanisms

Explain meiotic nondisjunction with a 2n egg and n pollen

2n (egg) + n (pollen) = 3n plant

Explain mitotic nondisjunction with a 2n cell

2n cell that is nondisjunctioned = 4n cell

Explain how mitotic and meiotic nondisjunction with a 2n egg and n pollen

2n (egg) + n (pollen) = 3n = 6n

How does allopolyploid lead to infertility?

nonhomologous chromosomes may have difficulty pairing in meiosis

How does chromosome nondisjunction in allopolyploids lead to fertility?

chromosome nondisjunction leads to cells with double the number of chromosomes so that now each chromosome has a homolog for pairing

What are the three consequences of polyploidy?

fruit and flower size are increased; reduced fertility (unequal distribution of chromosome); and hybrid vigor

What is hybrid vigor?

greater growth, survival, and fertility of hybrids produced by crossing highly inbred lines

What is a chromosome break point?

location of chromosome break on DNA; ends at the breakpoint of a broken chromosome retain their chromatin structure, adhere to one another, other truncated chromosome ends, or to ends of intact chromosomes

What is a terminal deletion?

chromosome break that detaches all or part of one arm of a chromosome including the telomere

What is an acentric fragment and what does it do?

chromosome fragment without a centromere; can be lost during cell division, lacks kinetochore so it cannot migrate to a pole of the cell during division

What are partial deletion heterozygotes?

loss of a segment of a chromosome that results in partial monosomy for the affected chromosome segment (one WT chromosome and a homolog with a terminal deletion)

What is an interstitial deletion?

loss of an internal segment of a chromosome from within one arm; results from two chromosome breaks followed by joining of the ends from either side of the lost segment

What is an example of a syndrome resulting from a partial deletion heterozygote?

cri-du-chat syndrome; loss of 5p15.2-5p15.3

What is an example of a syndrome caused by an intersitital deletion?

WAGR syndrome; results from interstitial deletion of multiple genes on chromosome 11 (11p1.3-11p2)

What is an unequal crossover?

results form improper synaptic pairing of homologous chromosomes and crossing over between the mispaired chromosomes; source of duplication and deletion genetic material

What is partial duplication?

duplication of a segment of a chromosome

What is partial deletion?

organism with one WT chromosome and homolog that is missing a segment

What is a partial duplication heterozygote?

organism carrying one homolog with duplicated material

How are larger deletions or duplications of chromosome segments detected?

microscopic examination that reveals altered chromosome banding patterns resulting from structural change to the chromosome

What are microdeletions and microduplications?

small deletion/duplication only detectable by molecular methods of analysis

What is an unpaired loop?

at synapsis involving a partial deletion or partial duplication of one chromosome of a homologous pair, the extra material that does not have a homolog on the paired chromosome

What is pseudodominance?

phenotypic expression of a recessive allele on one chromosome due to deletion of a portion of the homologous chromosome containing the dominant allele

What is deletion mapping?

method for mapping genes utilizing partial chromosome deletions with known locations to expose recessive mutants by pseudodominance

What is chromosome inversion?

structural alteration of a chromosome in which a segment breaks away from the chromosome and reattaches after a 180^o rotation

What is chromosome translocation?

relocation of a chromosome fragment to a non-homologous chromosome

What are the two different types of chromosome inversion?

paracentric and pericentric inversion

What is paracentric inversion?

results from inversion of chromosome segment on a single arm and does not involve the centromere

What is pericentric inversion?

reorients a chromosome segment that includes the centromere

What are inversion heterozygotes?

organisms whose homologous chromosomes have different structural organization; one has normal structure whereas the homolog carries an inversion

What is an inversion loop?

structure that forms by the looping of one chromosome to align homologous regions in an inversion heterozygote

What is a dicentric chromosome?

chromosome with two centromeres

What is a dicentric bridge?

portion between two centromeres in a dicentric chromosome that are drawn to opposite poles of the cell during division

What is the result of crossover in the inversion loop in paracentric inversion heterozygotes?

one normal chromosome (viable), two deletion chromosomes/fragments (nonviable), and an inversion chromosome (viable)

What is the result of crossover in the inversion loop in pericentric inversion heterozygotes?

one normal chromosome (viable), two duplication/deletion chromosomes (nonviable), one inversion chromosome (vaible)

What are the three facts about recombination in inversion heterozygotes that have important genetic implications?

probability of crossover within the inversion loop is linked to the size of the inversion loop; inversion suppresses the production of recombinant chromosomes; fertility may be altered if an inversion heterozygote carries a very large inversion

What is crossover suppression?

reduction of absence of progeny with recombinant chromosomes due to duplications and deletions of genetic material following crossing over within the inversion loop in organisms that are heterozygous for an inversion

What are translocation heterozygotes?

organism with chromosome translocation in which chromosome pairs consist of one normal chromosome and a homolog carrying a translocation

What are the three types of translocation?

unbalanced, reciprocal balanced, and robertsonian

What is unbalanced translocation?

chromosome break and subsequent reattachment of the fragment to a nonhomologous chromosome in a one-way event

What is a reciprocal balanced translocation?

produced when breaks occur on two nonhomologous chromosomes and the resulting fragments switch places when they are reattached

What is Robertsonian translocation/chromosome fusion?

fusion of two nonhomologous chromosomes; accompanied by loss of one of the centromeres and loss of a chromosome short arm; usually acrocentric or telocentric chromosomes

What happens in reciprocal balanced translocations?

none of the four chromosomes have a fully homologous partner; unusual cross-like structure is formed at metaphase of meiosis; three patterns of segregation are possible in anaphase I (alternate, adjacent-1, and adjacent-2 segregation)

What is alternate segregation?

two normal chromosomes move to one pole of the cell and the two translocated chromosomes to the other

What is adjacent-1 segregation?

one normal and one translocated chromosome move to each pole of the cell

What is adjacent-2 segregation?

very rare; homologous centromeres move together to each pole of the cell

What is the consequence of alternate segregation?

gametes formed contain a full haploid set of genes

What is the consequence of adjacent segregation?

gamete contains two copies of some genes and complete absence of others

Why are translocation heterozygotes semi-sterile?

only alternate segregation leads to normal gametes

What does the chromosome number decrease to in Robertsonian translocation?

2n-2; each chromosome of pair “a” fuses to a different chromosome of pair “b”

What is a histone protein?

five proteins that are positively charged and bind tightly to negatively charged DNA (1/2 of the protein content of chromatin)

What are the five different histone proteins?

H1, H2A, H2B, H3, H4

What are nonhistone proteins?

numerous nuclear proteins that are not histones associated with chromosomes

What is the nucleosome core particle?

fundamental units of histone protein organization with two molecules each of histones H2A, H2B, H3, and H4 (octamer) with DNA of 146 bp (core DNA) wrap around each octamer

How is a nucleosome assembled?

histones H2A and H2B assemble into dimers; H3 and H4 form dimers; two H3-H4 dimers form a tetramer, after which two H2A-H2B dimers associate with it to form the octamer; wrapping of DNA around the octamer is the first level of DNA condensation and compacts the DNA sevenfold

What is the structure of chromatin?

“beads on a string” (10nm); beads are nucleosomes and string is linker DNA

What is linker DNA?

DNA between regions of core DNA

What is the solenoid structure?

under in vitro conditions when a 30nm fiber forms to coil into this structure with 6-8 nucleosomes per turn as histone H1 stabilizes the structure

Describe in what phases chromatin is condensed in

exists in a 30nm fiber or more condensed state during interphase and becomes maximally condensed during metaphase of mitosis