Chromosomes (rearrangements) Flashcards
what are the two basic types of human chromosomes?
autosome
sex
autosome chromosomes
identical in both males and females; numbered by size (22 out of 23)
sex chromosomes
23rd pair that differs between males and females (females: XX; males: XY)
how many chromosomes do each human cell have?
23 pairs of chromosomes –> 46 total chromosomes
karyotyping/karyotype
karyotyping: the process of sorting human chromosomes pairs by size and morphology
karyotype: human chromosomes lined up in pairs
Chromosome painting
using probes (aka fluorescent DNA molecules) to bind to specific sequences on Chr → when viewed under a fluorescence microscope, they “paint” the Chr in different colors (can detect chromosomal rearrangements)
somatic cells
body cells (ie. muscle, skin, blood)
Contains a complete set of chromosomes (26 in humans)
are diploid cells
diploid cells
In each diploid cell, humans have 23 homologous pairs (aka homologs) → total 46 chromosomes
In diploid cells, one set of chromosomes is inherited from the mother and the second is inherited from the father
Total number of chromosomes in diploid cells → described as 2n
what are homologs (homologous pairs of chromosomes) and how can they differ among each other?
Think of homologs as a matching set: they are NOT exactly identical
Approximately same length, centromere position, and staining pattern
The maternal and paternal chromosomes in a homologous pair have the same genes at the same locus BUT possibility DIFFERENT ALLELES
One homolog from mother, one homolog from father
During meiosis, homologs pair together
the maternal and paternal chromosomes in a homologous pair have the same ___ at the same ___ BUT possibility DIFFERENT ___
genes, locus, alleles
what are the two types of human cells?
somatic (body) cells: diploid
sex cells: haploid
sex cells
cells in the germ line (produces gametes, or egg and sperm cells)
Female gametes: ova or egg cells
Male gametes: sperm
Are haploid cells
haploid cells
In each haploid cell, human sex cells have TOTAL of 23 chromosomes (since they aren’t paired)
Total number of chromosomes in diploid cells → described as n
what are the components of chromosome structure?
Centromere: divides the chromosomes into the “p” arm (small) and “q” arm (long)
Telomeres: at both ends of each chromosome
Chromatid: one of the two identical copies/halves of a chromosome
where are chromosomes found in the cell?
nucleus
how is each band within a region numbered? (directionality)
Each band within a region is numbered centromere TO telomere
“p” arm vs “q” arm
“p” arm (small) and “q” arm (long)
band nomenclature: ie. q21.1
“q-two-one-point-one” = q arm, region 2, band 1, subband 1 (NOT q-twenty-one-point-one)
what are the effects of chromosomal rearrangements?
Change chromosomal structure
Can alter the function of one or more genes and can change the pattern of gene transmission
how do transposable elements cause chromosomal rearrangements?
transposable elements (aka jumping genes): DNA sequences that can change their position within the genome, potentially altering the function and regulation of genes
Transposable elements can insert into genes → alter their function and can cause chromosomal rearrangements
what are the four types of chromosomal rearrangements?
Deletion (deficiency): removes a segment of DNA
Duplication: results in an increase in copy number of a particular chromosomal region (occurs in ALL organisms)
Inversion: a segment of chromosome is reversed end to end (rotated 180 degrees)
Translocation: the exchange of genetic material between 2 NON-HOMOLOGOUS chromosomes
interstitial vs terminal deletions
Interstitial: deletion located WITHIN a chromosome
Terminal: deletion that removes the END of a chromosome
intragenic vs multigenic deletions
Intragenic: small deletions only affecting ONE gene
Multigenic: deletions that span MULTIPLE genes
homozygous deletion (del/del)
Occurs when BOTH alleles of a gene are deleted from an individual’s chromosomes
If deleted region does NOT contain any genes essential for survival → an individual homozygous for a deletion will live
Large deletions spanning multiple genes → results in homozygous lethality (removing essential genes)
Heterozygous deletion (Del/+)
Occurs when only ONE allele of a gene is deleted while the other allele remains intact
Some heterozygotes are viable and fertile, but other instances might be detrimental
In general, humans cannot survive even as heterozygotes with deletions that remove more than around ___ of the genome
3%
what is an example of a heterozygous deletion?
‘Cri du chat’ syndrome (aka ‘5p minus’ syndrome): a deletion of all or part of the short p-arm of chromosome 5 → often don’t live past childhood
what is an example of a duplication?
red-green color blindness (aka daltonism)
the OPN1LW (red) and OPN1MW (yellow, green) genes are located
on the X chromosome –> affects more men than women
chromosomal inversions
A rearrangement in which a segment of chromosome is reversed end to end (rotated 180 degrees)
Occurs when TWO breaks occur within ONE chromosome → the genetic material in between the breaks in inverted
Relatively rare events and unlikely that multiple patients with the same inversion are found
EXCEPTION: if the inversion breakpoint falls within or near a gene that has previously been associated with the disorder through other types of mutations
what are the 2 types of inversion mutations?
pericentric
paracentric
what is an example of inversion mutation?
hemophilia A: recurrent inversion mutations in the coagulation factor VIII gene on the X chromosome causes hemophilia A (also caused by mobile genetic element-induced mutations)
individuals with hemophilia A experience prolonged bleeding because their blood doesn’t clot properly –> can lead to excessive bleeding from even minor injuries, and, in more severe cases, spontaneous bleeding (internal bleeding without any clear injury).
pericentric vs paracentric inversion mutations
Pericentric: break occurs between TWO arms of a chromosome and the inverted segment DOES include the CENTROMERE (remember: pEri → cEntromere)
Paracentric: a break to only ONE arm of chromosome and inverted segment does NOT include centromere
reciprocal translocation
a two -way translocations: exchange chromosomal segments between 2 DIFFERENT (non-homologous) chromosomes → often balanced
Most typical type of translocation
what are the three types of chromosomal translocations?
reciprocal
nonreciprocal
robertsonian
- occurs between non-homologous chromosomes
balanced translocation
when the 2 breaks do NOT pass through a gene and there is NO GAIN or LOSS of material
nonreciprocal translocation
one-way translocation: transfer a chromosomal segment from one chromosome to a NONHOMOLOGOUS chromosome → receiving chromosome becomes longer than normal/original size and the transferring chromosome becomes shorter
robertsonian translocations
Usually occurs in acrocentric chromosomes (small p-arm: ie. 13, 14, 15, 21, 22)
Most common kind of chromosome rearrangement known in people: about 1 of 1000 newborns have this type of translocation
balanced form
unbalanced form
what are the two forms of robertsonian translocation?
Balanced form: normal phenotype
Reciprocal exchange between 2 acrocentric chromosomes → results in…
1 large metacentric chromosome (fusion of the long q arms) and 1 very small chromosome (fusion of the short p arms) –> this chromosome carries so few genes that it does NOT cause genetic imbalance (only loses from 46 → 45 total chromosomes)
Unbalanced form: produces chromosome imbalance
Causes multiple malformations and mental retardation
give two examples of robertsonian translocations
- trisomy 13 (patau syndrome): extra copy of Chr 13 (usually lethal within 1yr if infant survives to even be born)
- trisomy 21 (down syndrome): extra copy of Chr 21 (t(14;21))
A man with robertsonian translocation on Chr 21-14 marries healthy woman.
Probability to have a down syndrome child:
Probability to have a healthy child (no carrier):
Probability to have a child with the Roberstonian carrier (but live, normal):
Probability to have a down syndrome child out of the alive children:
Probability to have an alive child:
Probability to have a carrier child out of the live child:
Probability to have a down syndrome child: 1/6
Probability to have a healthy child (no carrier): 1/6
Probability to have a child with the Roberstonian carrier (but live, normal): 1/6
Probability to have a down syndrome child out of the alive children: 1/3
Probability to have an alive child: 1/2
Probability to have a carrier child out of the live child: 1/3
what are 2 chromosomal translocations found in cancer?
- Chronic myeloid leukemia (CML):
- Alveolar rhabdomyosarcoma (ARMS)
Chronic myeloid leukemia (CML)
Chr 9 (region q34) and Chr 22 (region q11) → t(9;22)(q34;q11)
- the ABL1 gene normally on Chr 9; BCR gene normally on Chr 22
–> results in an oncogenic BCR-ABL1 gene fusion, which creates a philadelphia chromosome (PH or Ph’) which is talking about the changed Chr 22
Alveolar rhabdomyosarcoma (ARMS)
Translocations → causes the fusion (chimeric) gene: t(2;13)(q35;q14) → PAX3-FOXO1
ARMS having the fusion gene → worst clinical outcome
Chromosomal translocation nomenclature: t(9;22)(q34.1;q11.2)
First set of parentheses = the chromosomes involved
9 = first chromosome involved;
22 = second chromosome involved
Second set of parentheses = the chromosome bands involved + indicates the breakpoints on the arms
q34.1 = q-arm region 3 band 4 sub-band 1
q11.1 = 1-arm region 1 band 1 sub-band 2
What are acrocentric chromosomes and some examples?
chromosomes with a short p-arm
Chr 13, 14, 15, 21, 22
What is the most common kind of chromosome rearrangement known in people?
robertsonian translocations (1 in 1000 newborns)
What is the most typical type of translocation?
reciprocal translocations
what are the chromosomes involved in trisomy 13 (patau syndrome)?
Chr 13 and Chr 14 (extra copy of Chr 13)
what are the chromosomes involved in trisomy 21 (down syndrome)?
Chr 14 and Chr 21 (extra copy of Chr 21)
What does a carrier of trisomy 13 and trisomy 21 look like?
carrier of trisomy 13 and trisomy 14 is the balanced form of Robertsonian translocation
trisomy 13: 1 Chr13, 1 Chr 14, 1 metacentric Chr of 13&14
trisomy 21: 1 Chr14, 1 Chr 21, 1 metacentric Chr of 21&14
–> the total number of each type of chromosome is still 2 of each which is why they have normal phenotype
What does an affected individual with trisomy 13 or trisomy 21 look like?
trisomy 13: 1 Chr 13, 1 Chr 13, 1 combined Chr of 13&14, 1 Chr 14
–> net: 3 Chr 13, 2 Chr 14
trisomy 21: 1 Chr 21, 1 Chr 21, 1 Chr 14, 1 combined Chr of 14&21
–> net: 3 Chr 21, 2 Chr 14
