Lecture 46: Structural Chrom Abnormalities Flashcards
Reciprocal Translocation
-Exchange of genetic material between non-homologous chroms (diff chroms)
Possible Effects:
- Silent = normal
- Cancer/incr. growth of cells
- Spontaneous abortion
Examples Translocations:
- t(9;22)
- t(8,14)
- t(9;22): (philadelphia chrom)
- Activation of BCR-ABL tyrosine kinase made + stimulates uncontrollable cell division = CANCER
- t(8,14): (Burkitt Lymphoma)
- Disreg of c-Myc = gene expression alway on = CANCER
Robertsonian Translocation
Outcomes
- Between acrocentric chroms 9, 13, 14, 15, 21, 22
- Loss of short arms of the two chroms
- Fusion of long of the two chroms
-Both go through meiotic pairing
Outcomes:
1) Alternate segregation = compatible with life
-Normal gamete (Gamete 1)
-Translocation carrier (Gamete 2) on fertilization
(balanced chrom material)
2) Adjacent segregation = Not compatible with life
-Result in syndromes:
-Trisomy 14= (Gamete 3)
-Trisomy 21 = (Gamete 4)
(unbalanced chrom material)
Microdeletion syndromes
1) Large deletions (>5Mb)
- Test by karyotype
- Must effect band pattern
- However some very large deletions appear normal
2) Small deletions (<4Mb)
- Test by FISH
*Microarray can detect common deletions and small deletions/duplication
Microarray CGH
- Each spot on the array is an immobilized probe for a specific place in the genome
- Allows the use of almost a million probes = HIGH DENSITY
Cri-du-chat Syndrome
- Deletion of chrom 5p
- 46, XX, del(5)(p15.3)(pter) or 46,XY del(5)(p15.3)(pter)
Symptoms:
- High pitched cat like cry
- Speech problems later in life
- Sever intellectual disability
- Microcephaly
- Hypertelorism (widely spaced eyes)
Testing:
- Sometimes detected by Karyotype, but not always
- FISH and Microarray CGH can detect
22q11.2 Deletion Syndorme
- Degeorge Syndrome
- Microdeletion of chrom 22q11.2
Symptoms:
- Congenital heart defects
- Absence of thymus
- Cleft lip and palate, speech problems
- Learning disability
- Facial abnormalities
Testing:
- Detected by FISH
- Comparitive geonome hybridization can detect
Wolf-Hirschhorn Syndrome (WHS)
-Deletion of chrom 4p
Symptoms:
1) Seizures
2) Skeletal abnormalities and congenital heart defects
3) Intellectual delay (mild-severe)
4) Facial anomalies:
- (widely spaced eyes
- high arched eye brows
- broad and flat nasal bridge
- ROMAN HELMET
- Small chin
Deletions in Chrom 15:
15q11 to 15q13
- Results in Prader Willi and Angelman Syndrome
- Can also develop from uniparental disomy of chrom 15
Prader Willi:
- Paternal chrom deletion (SNRPN)
- Methylated maternal SNRPN
Angleman:
- Maternal chrom deletion (UBE3A)
- Methylated paternal (UBE3A)
Uniparental Disomy of Chrom 15:
- Inheritance of both chrom 15 from the same parent)
- Can be due to Trisomy rescue (kicks out extra chrom)
- Prader = Inheriting both maternal chrom 15’s
- Angelman = Inheriting both paternal chrom 15’s
Structural abnormalities:
Inversion
1) Pericentric = centromere
2) Paracentric= no centromere involved
During crossing over in Meiosis:
- Can result in duplications or deletions of chrom
- high risk of spontaneous abortions
Structural abnormalities:
Isochromosomes
- Loss of one arm of a chrom and duplication of the other
- X isochromosome: long arm of the X chrom join to form isochromosome
Effects:
- Gene dose imbalance
- Usually lethal (but mosaic can be tolertated)
-Some children w Turners syndrome have this on one of the x chroms (One copy of short arm chrom, isochrom = inactive, haploinsufficiency)
Structural abnormalities:
Ring Chromosomes
-Chrom loses genetic material at the terminal portion and the end fuses to = ring structure
