Things to Remember Flashcards
Chromosomes with C bands (hotspots for human specific evolutionary change)
1, 9, 16, and Y
2 factors that influence nondisjunction
- Nondisjunction events are related to the positioning of chiasmata; crossover events that occur too near or too far from the centromere increase chromosome nondisjunction.
- Nondisjunction events are also related to the frequency of crossover events. The reduction or absence of recombination events increases the likelihood of nondisjunction.
t(9;22)
diagnostic for chronic lymphocytic leukemias (CML), which can be treated with a specific tyrosine kinase inhibitor, Imatinib mesylate, also known as Gleevec
t(15;17)
diagnostic for a specific acute myeloid leukemia (AML), which can be treated with retinoic acid and arsenic trioxide
3 types of FISH probes
- centromere (cen)
- Locus Specific Identifier (LSI)
- Fusion (F)
Centromere FISH probe is used for:
Enumeration
ALL, Cen 8,21
LSI FISH probe is used for:
Deletion/Duplication
p53; N-myc;Her2/neu
F FISh probe is used for:
Translocations
(BCR;ABL t(9;22)
PML;RARA t(15;17))
CMA can detect ____ and ____ but not ____
deletions, duplications
NOT translocations
Frequent location of a Robertsonian translocation
chr.14 - chr. 21 fusion. Notice this often results in trisomy 21 (gamete has the copy of chr. 14 with 21 stuck onto it as well as the normal copy of 21).
Two types of chromosomal deletions
- Terminal deletion
2. Interstitial Deletion
Contiguous gene syndrome
Disorder due to overexpression or deletion of multiple gene loci that are adjacent to one another.
Ex: Velocardiofacial syndrome (del 22q11) and DiGeorge syndrome (del 22q11)
DNA Methylation as the Epigenetic Mark
- The modification must be established in the gametes, the point in time when the maternal and paternal alleles are in separate compartments and can be differentially modified.
- The allelic modification must be stably maintained after fertilization.
- The modification must be capable of being erased and reset during the production of the germ cells such that the appropriate sex-specific imprint is transmitted to the progeny
In somatic cells, methylation is maintained by which enzyme?
maintenance methyltransferase
Mechanism of methylation in germ line
whole scale erasure of all of the methylation marks leads to demethylation of chromosomes, x chromosome reactivation and biallelic expression. Then, remethylation occurs through denovo methyltransferases happens in a sex specific manner. Occurs prior to initiation of meiosis in primordial germ cells.
Testing for Down Syndrome
amniocentesis at 16 weeks
chorionic villus sampling at 11-12 weeks
Physical features of a patient with Down Syndrome
Normal growth parameters, brachycephaly, mid face hypoplasia, up-slanting palpebral fissures, epicanthal folds, Brushfield spots, dysplastic small pinnae, heart murmur may be present, genitalia may be abnormal, especially in males (undescended testicles, small phallus, hypospadias), incurving 5th finger, small digits, increased space b/w 1st and 2nd toes, increased joint range of motion, diffuse hypotonia
Medical conditions and prevalence of these conditions in patients with DS
- Congenital heart disease (1/3-1/2 of babies). Endocardial cushion defect, which is also called atrioventricular canal (AVC).
- GI tract defects: 10-15% of babies with DS. Esophageal or duodenal atresias, which leads to polyhydramnios during pregnancy.
- Both require surgical repair.
- Others: Small tear ducts, small eustachion tubes, small airway, eye problems (stabismus, nysatmus, cataracts, myopia), ear problems (infections, hearing loss), thyroid problems, celiac disease, diabetes, feeding issues, GERD, constipation, intellectual disabilities, autism, depression, Alzheimers.
Understand why many biochemical variants are not deleterious.
- Degeneracy of genetic code
- “Like” amino acid replacement is often unnoticed
- Amino acid replacement in the “non-business” portion of protein may not markedly influence function
- Most importantly, Man is diploid for autosomal genes and thus has multiple
alleles for most proteins.
Gene rich chromosome
19
Gene poor chromosomes
13, 18, 21
Unstable region of Chr 5q13 is associated with
Spinal muscular atrophy (SMA)
unstable region of Chr 22q is associated with
DiGeorge Syndrome
Alu family
SINEs
300 bp related members
500,00 copies in genome
