Structural Chromosomal abnormalities Flashcards
Balanced
No gain or loss of genetic material
Unbalanced
Gain or loss of genetic material
Reciprocal translocation
Exchange of genetic material between non-homologous chromosomes
attach image from slide 8
What is this an image of ?
Balanced reciprocal translocation (chromosome 2 & 8)
What are the effects of reciprocal translocation in carriers?
May have no effect (silent)
Transformation to cancer and increased growth rate of cells
What if the reciprocal translocation is located in the germ line cells?
There is a higher incidence of spontaneous abortions in the carrier
Reciprocal translocation
Segregation at Meiosis
Reciprical Translocation creating a fusion gene
slide 13
t(9;22) –> Chronic Myelogenous Leukemia–> activation of an oncogene–> Cancer Philadelphia chromosome t(9;22)–> Activation of BCR-ABL tyrosine kinase which is a proto-oncogene in hematopoietic cells
Reciprocal translocation changing gene expression
t(8;14) —> Burkitt lymphoma Dysregulation of c-Myc gene expression, leading to cancer
Robertsonian translocation
- Occurs between acrocentric chromosomes
- Chromosomes 13,14,15,21,22
- There is loss of the short arms of the two chromosomes
- The satellite structures in the acrocentric chrome. contain multiple copies of genetic material for RNA
- Fusion of the long arms of the two chromosomes
What is this an image of ?
Robertsonian translocation- Effects during Meiosis
Robertsonian translocation alternate segregation
Normal gamete (gamete 1)
Gamete with the derivative chromosome(gamete 2) that results in a Robertsonian translocation carrier on fertilization
Robertsonian translocation: adjacent segregation
Results in trisomy of the respective chromosome on fertilization
Gamete 3 would result in trisomy 14, that is compatible with survival, and results in spontaneous abortion
Gamete 4 would result in trisomy 21(down syndrome) on fertilization
What accounts for 2-5% of children with Downs syndrome?
Robertsonian Translocation
Cri-du-chat Syndrome
Deletion of Chromosome 5p
46,XX,del(5)(p15.3)(pter)
46,XY,del(5)(p15.3)(pter)
Features of Cri-du-chat Syndrome
High pitched, cat like cry
micrognathia which influences the cat-like cry and speech problems later in life
microcephaly
hypertelorism(widely spaced eyes)
What is this Karyotype showing?
Cri-du-chat Syndrome
What is this CGH showing?
Cri-du-chat Syndrome
22q11.2 Deletion syndrome
Microdeletion of chromosome 22q11.2
DiGeorge syndrome, Velocardiofacial
Features of 22q11.2 Deletion syndrome
congenital heart defects
absence of thymus- can cause immunological problems
Cleft lip and palate- can lead to speech difficulty
learning disability
Increased risk of schizophrenia
Facial anomalies of 22q11.2 deletion syndrome
Long midface
narrow palpebral fissures
prominent nasal root
bulbus nasal tip
ear dysmorphology
What is this CGH showing?
Microdeletion of chromosome 22q11.2
What is this a FISH of ?
Microdeletion of chromosome 22q11.2
Wolf-Hirschhorn syndrome
Deletion of ch 4p
seizures
skeletal abnormalities and congenital heart defects
spectrum of intellectual and developmental delay(mild to severe)
what are the facial anomalies of Wolf-Hirschhorn syndrome
Widely spaced eyes
high arched eyebrows,
broad and flat nasal bridge (similar to roman helmet)
short philtrum
downturned mouth
small chin
Deletions in Chromosome 15q11-13
A few genes on chromosome q5 are monogenic( only one allele is expressed)
SNRPN and UBE3A
Prader willi and Angelman syndrome
Prader-willi syndrome
Deletion of Paternal chromosome 15q11-13 SNRPN
Angelmans syndrome
Deletion of maternal chromosome 15q11-13 UBE3A
Features of Prader willi
Eating disorder-hyperphagia
Developmental delays
hypotonia at birth
hypogonadism
distinctive facial features
Features of Angelmans syndrome
inappropriate laughing and smiling
jerky uncoordinated movement
lack of speech
hypotonia
severe developmental delay
Inversion abnormality
May be pEricentric ( involves the cEntromere)
paracentric (does not involve the centromere)
Usually result in a change in the banding pattern of the chromosome and can be identified by karyotype analysis
what is this an image of?
Pericentric inversion
what is this an image of?
paracentric inversion
Effects of inversion during meiosis
results in duplication or deletion of segments of the chromosome -unbalanced genetic material
The gametes with acentric and dicentric chromosomes are not viable
carriers of inversions may be asymptomatic but have a high risk of spontaneous abortions
Isochromosome
There is a loss of one arm of a chromosome and duplication of the other arm
Typically results in chromosomal and gene dosage imbalance
isochromosome of an autosome is lethal
x-isochromosome
Long arms of the X chromosome join to form an isochromosome
ring chromosome
Forms when a chromosome loses genetic material at the terminal portions and the ends fuse to form a ring like structure
