Transcript
Cytogenetics
What is Cytogenetics?
The study of chromosomes,
their structure, inheritance, and disorders
Chromosomal disorders occur in:
1% of all live births
2% of pregnancies in women over 35
50% of all 1st trimester miscarriages
(spontaneous abortions)
Cell types used for cytogenetic analysis
Must be capable of growth and rapid division in culture
Most commonly use white blood cells (T lymphocytes), extracted from whole blood samples.
Blood samples collected with heparin
to prevent clotting
White blood cells are separated by centrifugation
Cells are stimulated to divide in vitro
Cells are arrested in metaphase by addition of colchicine which inhibits the mitotic spindle
Cells are lysed to release chromosomes onto slides
Chromosomes are fixed & stained.
Clinical indications for Chromosome Analysis
Retardation of early growth & development without apparent cause
Repeated stillbirths, spontaneous abortions, & neonatal deaths
Fertility problems not due to obstructions or structural abnormality
Family History
Pregnant woman > 35 yr old
Neoplasia = Cancer
Failure to thrive, global developmental delay, unusual facial features, small head
10% have chromosomal abnormalities, karyotyping for parental genetics
3-6% chromosomal abnormalities is couples with infertility or multiple miscarriages
Known or suspected in 1st degree relative
Increased risk of chromosomal abnormalities
All cancers are associated with ?1 chromosomal abnormalities
Chromosome Identification by Size & Staining
G-banding = Geimsa stain
Chromosome Painting = Multicolor FISH
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Chromosome ID by Centromere Location
International Standard - Chromosome Nomenclature
Chromosome Abnormalities
Numerical = Aneuploidy
Abnormal chromosome number due to missing or extra chromosomes
Structural
Balanced
Reciprocal translocations (DNA exchange between non-homologous chromosomes)
Unbalanced
Deletions, inversions, insertions, rings
Variation in Chromosome Number
Variation in individual chromosomes
“-somy”
Variation in entire sets of chromosomes
“-poidy”
Generation of Aneuploidy
Trisomy 21 - Down Syndrome
1 in every 800 live births
250,000 individuals in the US
95% of nondisjunction in the ovum
Risk increases in mothers >35 yr old
Trisomy 13 – Patau Syndrome
Incidence: Live births ~ 1/15,000
90% mortality within 1st year
Characteristics: heart defects, brain & spinal cord abnormalities, microcephaly, polydactyly, small, poorly developed eyes, extra fingers or toes, cleft lip and palate, and weak muscle tone.
Trisomy 18 – Edwards Syndrome
Incidence: Live births ~ 1/7,500
95% spontaneous abortion
90% mortality within 1st year
Characteristics: mental retardation, failure to thrive, heart defects, receding jaw, low-set malformed ears, clenched fists, rocker-bottom feet, single crease on palms, unusual fingerprints (arches, no whorls)
Polyploidy
More than 2 sets of chromosomes
Found in lizards, amphibians and fish
Common in plants
Comai, L. The advantages and disadvantages of being polyploid. Nature Reviews Genetics 6, 839 (2005).
Autopolyploidy
Autotriploids
Sterile
Unbalanced Gametes
Autotetraploids
Fertile
Balanced Gametes
Allopolyploidy
Hybridization of two species
Allotetraploid most common
Also called amphidiploid
Usually fertile
Economic Importance of Polyploidy
{8A107856-5554-42FB-B03E-39F5DBC370BA}Apple, banana, seedless watermelons, ginger
Triploid
Apple, durum wheat, cotton, potato, cabbage, leek , tobacco, peanut
Tetraploid
Bread wheat, triticale, oat, kiwi
Hexaploid
Strawberry, sugar cane
Octaploid
Numerical Chromosome Abnormalities
Triploidy and Tetraploidy
Generally incompatible with human life
Triploidy observed in 1-3% conceptions
Result of fertilization by 2 sperm or failure of meiotic division in egg or sperm
Paternal = abnormal placenta & fetus
Partial Hydatidiform mole
Maternal triploidy = small placenta & fetus
Tetraploidy always 92 XXYY or 92 XXXX
Failure in early zygote cleavage
Mosaic = Individual with genetically different cell lines that arise from a single zygote
Chimera = Individual with genetically different cell lines that arise from more than one zygote or multiple fertilizations.
Mosaicism & Chimerism
Legendary Chimeric Pokemon
