Chromosomal Abnormalities Flashcards
What is the normal male karyotype?
46XY
What stain is used for G-banding?
Giemsa stain
What is a telomere and what is its function?
- DNA + protein cap
- Ensures DNA replication to tip
- Tether to nuclear membrane
What are light bands?
- Less condensed chromatin
- Transcriptionally active
- Gene + GC rich
What is the function of centromeres?
- Joins sister chromatids
- Essential for chromosome segregation at cell division
What are dark (G) bands?
- Condensed chromatin
- Gene poor, AT rich
What is Cytogenetic testing?
G banded routine karyotype
Karyotype = test of whole genome but normal result does not exclude genetic problem
What gene is CF, Huntington’s and SCA on?
CF = gene 7 Huntington's = gene 4 SCA = gene 11
What is the limit of detection of Karyotype resolution?
Able to see changes (e.g. deletion or extra piece) down to 5 million bases = limit, won’t see any smaller
What is DNA sequencing used for?
To look at DNA one base at a time
Name some cytogenetic techniques
Karyotype, FISH, Array-CGH
Name some molecular genetic techniques
MLPA, DNA sequencing
What is a Karyotype and what is the standard notation?
Karyotype = representation of person’s chromosome complement
Standard notation:
- total no. chromosomes
- followed by sex chromosome composition
- followed by any abnormalities detected
- changes in whole chromosome number (= chromosomal aneuploidy) = denoted using + or - sign against particular chromosome
Are trisomies viable?
No, common at conception only, never born
What is the only chromosomal monogamy survivable to term?
Turner syndrome (monosomy X)
What is a common mechanism of chromosomal aneuploidy?
Non-disjunction at meiosis (can occur in meiosis I or II)
What is Down syndrome?
Trisomy 21 - most common autosomal trisomy
How is Down syndrome detected?
- Structural abnormalities in antenatal scans, screening tests, or facial appearance at birth
- Increased nuchal translucency measurement @ 12 weeks
What is the presentation of Down syndrome in infants?
- muscle hypotonia
- large tongue
- umbilical hernia
- brush field spots
- single player crease
- congenital defects
What is the presentation of Down syndrome in adults?
- Developmental delay, intellectual disability
- Distinctive features - up slanting palpebral fissures, low-set ears, epicanthic folds, flattened nose, single transverse palmer crease, bilateral 5th finger clinodactyly, sandal gap deformity
- Short stature, obesity
- Increased risk congenital HD, thyroid disorders, conductive hearing loss, antlantoaxial instability, immune dysfunction, leukaemia, seizures, psychiatric illness, dementia
What is mosaicism?
Some of cells have genetic abnormality but also have proportion of cells without genetic abnormality.
Proportion can be high or low, can be throughout body or confined to particular section.
What is the effect of mosaicism?
- milder features (if mosaic with normal karyotype)
- can allow severe chromosomal abnormalities to be viable e.g. mosaic trisomy 8 and 22
- caused by post-zygotic errors in mitosis (nondisjunction or trisomy rescue)
What is germline mosaicism?
Mutated cells only present in person’s testis or ovaries.
Person may be completely asymptomatic but at risk of having multiple affected children.
What is Edward’s syndrome?
- Trisomy 18
- 2nd most common autosomal trisomy
- Majority miscarried or stillborn, some survive to 1 year
- IUGR
- Severe developmental delay
- Seizures
- Structural abnormalities - heart, eye, craniofacial, cleft lip/palate, urogenital, skeletal defects
- Arthrogryposis
- Clenches hands with index and 5th fingers overriding 3rd + 4th
- Rocker-bottom foot with prominent calcaneus
