Cytogenetics Flashcards
What is Xist?
An snRNA that “paints” the X chromosome to make it inactive
Located on the Q arm of the X chromosome
What is Tsix?
An antisense RNA that inhibits Xist, allowing the chromosome to become active.
What is Xite?
A transcription enhancer for Tsix
What are manifesting heterozygotes?
Females who express an X-linked disorder due to variations from random X-inactivation.
What is genetic imprinting?
Autosomal genes that are imprinted are epigenetically silenced.
“Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the female or male parent. Genes can also be partially imprinted.” - Wiki
What epigenetic mechanisms are present on an imprinted gene?
Methylation and hypo-acetylation
Maternal UPD (uniparental disomy) of chromosome 15:
Prader-Willi syndrome
Imprinting disorder arising from paternal deletion of chromosome 15
Paternal UPD (uniparental disomy) of chromosome 15:
Angelman syndrome
Imprinting disorder arising from maternal deletion of chromosome 15
During the G1 phase, genetic material is referred to as ______ ?
Chromatin, not visible by light microscopy.
What is the short arm of the chromosome called?
The P arm (petite)
What is the short arm of the chromosome called?
The P arm, which lies above the centromere
What is the long arm of the chromosome called?
The Q arm, which lies below the centromere
What are NORs?
Nucleolar organizer regions (NORs) are chromosomal landmarks that are made up of repeated ribosomal gene sequences (rRNA). They are located on the short arms (p arms) of acrocentric chromosomes, which include chromosomes 13, 14, 15, 21, and 22 in humans. NORs are visible on metaphase chromosomes as secondary constrictions.
How can polyploidy arise?
Due to polyspermia or meiotic failure
How does aneuploidy typically arise?
Meiotic non-disjunction during meiosis I produces 50% disomic and 50% nullisomic sperm.
Is the outcome of nondisjunction worse when it occurs in meiosis I or II?
The outcomes are worse when it occurs in meiosis I. When nondisjunction occurs in meiosis II, 50% sperm are euploid, 25% disomic, and 25% nullisomic
What is the only monosomy compatible with life?
Turner’s syndrome (45X), with 90-95% being spontaneously aborted.
What is trisomy 18?
Edward’s syndrome, second most common trisomy (1/6000 births). Most common trisomy in stillbirths, 12 months = typical lifespan. More common in females.
What is trisomy 13?
Patau syndrome. Typical lifespan = 24 months.
What are Robertsonian translocations?
Robertsonian translocation (ROB) is a chromosomal abnormality that occurs when the P arms of two different chromosomes fuse together end to end. This type of translocation only happens between acrocentric chromosomes 13, 14, 15, 21, and 22 because their short arms have similar DNA sequences that make them more likely to fuse.
Where is the PAR1 region located?
The distal p arm of both X and Y chromosomes. The SRY gene is just proximal to the PAR1 region.
What causes XX males and XY females?
When pseudoautosomal regions crossover below the SRY gene.
What genes escape X inactivation silencing?
Pseudoautosomal genes, which are necessary for synapsis and crossing over to occur.
Many genes related to nervous system development are not silenced, along with SHOX genes.
How does a reciprocal translocation affect meiosis?
Normal bivalents cannot form, instead qhuadrivalents form
What Robertsonian translocation most commonly leads to Down syndrome?
14;21 translocation
What Robertsonian translocation most commonly leads to Down syndrome?
14;21 translocation
How does Cri-du chat syndrome occur?
A deletion of the P arm on chromosome 5
What is a pericentric inversion?
A double break and reinsertion at the same chromosome (inverted) that Involves the centromere
What is a paracentric inversion?
A double break and reinsertion at the same chromosome (inverted) that does not Involve the centromere
What genetic mutation is responsible for retinoblastoma?
Deletion in the Q arm at chromosome 13
What genetic mutation is responsible for retinoblastoma?
Deletion in the Q arm at chromosome 13
What genetic mutation is responsible for chronic myelogenous leukemia?
Reciprocal translocation between chromosomes 9 and 22
22 - Philadelphia chromosome
The break point cluster gene of 22 fuses with the Abelson oncogene of 9. This codes for a constitutively active tyrosine kinase.
What is constitutive heterochromatin
Highly repetitive/condensed and never transcribed, replicates late in the S phase.
What is facultative chromatin?
DNA sequences that may be active in one cell and inactive in another. The inactive X chromosome is an example of facultative heterochromatin.
Give an example of constitutive chromatin
DNA encoding the cetromere
47 XXY or 48 XXXY
Klinefelter syndrome
45 XY t(13,15)
Probably normal male phenotype, may have difficulty with having children.
What is dosage compensation?
Females dosage compensate and do not transcribe as much gene product from the X chromosome as compared to a male X chromosome.
Where is the BCR gene found?
The breakpoint cluster region is found on the proximal Q arm of chromosome 22.
Although a reciprocal translocation typically is phenotypically normal, when gametes are formed and fertilized, problems can arise due to homologous recombination of the translocated chromosomes. What are the potential manifestations of meosis producing gametes with unbalanced translocations?
Partial trisomy or partial monosomy
What is the difference when the t(14,21) reciprocal translocation is located in the DNA of male vs female when trying to have children?
When the translocation is maternal 10% DS Risk = 0.33
vs. paternal 2% DS risk = 0.007
What is the risk when a female has 21:21 Robertsonian translocation to have a baby with DS? When male has normal karyotype.
100% probability, female is going to be giving two copies of each allele on chromosome 21.
What is mosaicism?
Mosaicism or genetic mosaicism is a condition in which a multicellular organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg.
