Clinical Cytogenetics Flashcards
What is the p arm?
The shorter arm in a chromosome
*Centromere in the middle
What is the q arm?
The longer arm in a chromosome
What is metacentric?
The centromere is a little off set
What is Submetacentric?
The centromere is closer to the end toward the p arm
What is Acrocentric?
The centromere is very close to the end of the p arm
What is telocentric
The centromere is all the way to the end of the p arm (No p arm)
*No telocentric in HUMANS (only mice)
What is Karyotype?
- Arrange chromosomes by size and position of centromere (arranged in descending order)
- 46 chromosomes (diploid)
- 22 pairs of autosomes
- 2 sex chromosomes
*Ideogram is organized by size
What is Giemsa or G-banding?
- Pretreat with typsin to digest protein
- Stains AT rich region
- Inexpensive
What are 3 types of stains for visualizing chromosomes?
- Giemsa or G banding
- Quinacrine or Q-banding
- Reverse or R-banding
What is Quinacrine or Q-banding?
- Stains AT rich regions
2. Visualize with ULTRAVIOLET LIGHT
What is Reverse or R-banding?
- Uses Giemsa
2. Chromosomes treated at HIGH TEMPERATURE and LOW pH
What is Aneuploidy?
Change in the copy of individual chromosomes (Trisomy 21)
What is Fluorescent In Situ Hybridization (FISH)?
Labeling a region with a fluorescent probe detected with a fluorescent microscope
What is Chromosome Painting or Spectral Karyotyping (SKY)?
Labeling for each chromosome with a separate color detected with a spectrophotometer
How do you identify a chromosome?
- By Chromosome number
- Region
- Band
- Sub-band
Ex: Chr 16p11.2
a. Chromosome 16
b. Region 1
c. Band 1
d. Sub-band 2 on the p arm
What are 3 structural changes in chromosomes?
- Deletions/Addition
a. Single nucleotides
b. Several nucleotides
c. Microdeletion syndromes - Duplications
- Rearrangements (translocation: one piece of a chromosome gets stuck to another)
What is Rearrangements?
- Two types
a. Balanced
b. Unbalanced
What is Balanced rearrangement?
- All genetic information is present in this individual
- However, a problem might be present in the offspring
- Reciprocal translocation
What is Unbalanced rearrangement?
- Genetic information is missing
What is Mosaicism?
Cells should have one compliment of DNA
*Mosaicism occurs when an individual has
two or more cell lines that are derived from
a single zygote but that have different genetic
characteristics.
What is Chromosomal Mosaicism?
- Presence of an extra chromosome
2. Development of a new mutation during early development
What is Germline Mosaicism?
- Mutation occurs in a developing germ cell that is not present in other parental cells
What is a Barr Body?
- Identified by Murray Barr (dark staining body in interphase cells)
- Also Known as Sex chromatin (One X chromosome in each cell is inactivated, and condensed)
- Normal females: 1 Barr Body
- Normal Males: NO Barr Body
What is Lyonization?
- Barr bodies is an extra X chromosome
- The X chromosome are inactive (occurs in blastocyst; early development)
*Lyon Hypothesis: explains dosage compensation in males and females
How does Inactivation Chromosomes occur?
- X-Chromosome Inactivating Center (XIC) occur at the proximal end of Xq
- XIST Gene within the XIC
- XIST RNA binds to X Chromosome to inactivate it
What is nondisjunction?
- When chromosomes in Meiosis 1 doesn’t separate (Two “x” chromosomes are stuck together and continue to meiosis 2)
What is Etiology?
Nondisjunction
What is Trisomy 13?
- Third most common trisomy; “Patau syndrome”
- 50% die by age 1; 75% die by 6 months
- Trisomy 75-80%
*The more normal the mosaic the more physically normal the baby will be
What is Trisomy 18?
- Second most common; “Edwards syndrome”
- 90% die by age one
- Trisomy: 95%
What is Trisomy 21?
- Most common live born trisomy (DOWN SYNDROME)
- Trisomy: 93%
*The smaller the chromosome thats being affect the more dangerous the condition
What is Microcephaly?
Small head
What occurs in Trisomy 13?
- Severe intellectual and motor development delay
- Seizures
- Microcephaly
- Scalp defects (Absent skin)
- Microphthalmia (eye disorder)
- Cleft lip/palate
- Congenital hearts (80%)
- Dextrocardia (heart on the wrong side of the body)
- Omphalocele (belly button outty)
- Holoprosencephaly (no separation between the two hemispheres of the brain)
- 25% have extra toes
*Trisomy 13: 47,XX+13
What is Trisomy 18?
- Clenched fist (trigger finger)
- Intrauterine growth retardation (IUGR)
- Rocker bottom feet(no arch on the foot)
- Low set ears
- Cardiac defects
- Renal anomalies
- Intellectual development delay
- Broad forehead
- Sternum is short
- Missing toenails
*Trisomy 18: 47,XY+18
What is “General Failure to Thrive”?
- Cardiac and renal malformations
- Feeding difficulties
- Sepsis
- Apnea caused by CNS defects
What is Trisomy 21?
- Down syndrome (translocation most common; instead of true 21)
- Intellectual development
- Short stature
- Brushfield spots (on the eye)
- Simian crease (one line on the hand)
- Wide space between toes
- Poor muscle tone
- Small ears
What are 3 most important translocations?
- Down syndrome
- Chronic myelogenous leukemia
- Burkitt lymphoma
What is Klinefelter Syndrome?
- Trisomy
- Common cause for male hypogonadism
- 47, XXY (XXXY-Lyonization )
- Birth and childhood normal
- Puberty- may be delay (shows until the blastoid stage)
- Small penis/testes
- Elevated gonadotropin levels
- Infertility
- Decrease testosterone levels
- Decrease facial/pubic hair
- Abnormal skeletal proportions (lower segment is larger)
- Dissocial behavior
- Increased risk for autoimmune disorders (diabetes)
What are monosomies?
- Autosome monosomies are lethal
- Y Chromosome monosomy is lethal (45, Y)
- X Chromosome monosomy is viable (45, X)
What is Turner Syndrome?
- Monosomy (45,X)
- Normal intelligence
- Lack of ovarian development (NEVER HAVE A MENSTRUAL CYCLE)
- Elevated LH/FSH
- Webbed neck
- Shield-like chest with widely spaced nipples
- Edema of hands and feet
- Decreased Estrogen
- Infertile
*Increased diabetes mellitus, inflammatory bowel disease, and autoimmune disease
What is Uniparental Disomy?
The situation in which 2 copies of a chromosome come from the same parent,
3. Nondisjuction
Ex: Angelman syndrome (AS) and Prader-Willi syndrome (PWS)
*CpG Island Methylation: Inhibits Transcription
What is Genomic Imprinting?
The expression of a gene is dependent upon the parent of origin
What is Disomy?
2 chromosomes from the same parent
What is Isosomy or isodisomy?
2 identical chromosomes from same parent
*Nondisjunction in meiosis 2
What are the 2 first microdeletion syndromes recorded?
- Prader Willi Syndrome
- Angelman Syndrome
*Chromosome 15q11-15 deletion
What is Prader Willi Syndrome?
- Deletion of paternal origin (Large deletion of SNRPN and UBE3A)
- Hypotonic (no muscle tone)
- Feeding difficulties
- Hypogonadism (micro-gonads)
- Scoliosis
- Almond shaped eyes
- Small hands and feet
- Obesity
*Patients scratch themselves
What is Angelman Syndrome?
- Deletion of the Maternal Origin (deletion of SNRPN and UBE3A)
- Severe developmental delay and intellectual disability
- Severe speech impairment
- Microcephaly
- Inappropriate happy demeanor
