Lecture 24 Flashcards
What is a euploid ploidy?
A euploid ploidy means having an exact multiple of the haploid number of chromosomes. Normal gametes have the haploid number of chromosomes for humans: N = 23. A normal somatic cell is Diploid 2N = 46
What is polyploid ploidy?
Polyploid cells and organisms are those containing more than two paired sets of chromosomes.
3N = triploid: Meiosis division failure
4N = tetraploid: 1st mitotic division failure
What is aneuploid ploidy?
Any non-euploid number of chromosomes, resulting from nondisjunction of a single pair of homologous chromosomes during meiosis (ex: Trisomy, monosomy)
What is trisomy ploidy?
The presence of an extra copy of a single chromosome in a zygote
What is monosomy ploidy?
The absence of a single chromosome in a zygote
When does meiotic aneuploidy occur?
During an error in meiosis 1 or meiosis 2
What is the result of meiotic 1 aneuploidy?
1) Two Disomic gametes (each have 2 sets chromosomes instead of 1)
2) Two Nullosomic gametes (each have 0 sets chromosomes instead of 1)
What is the result of meiotic 2 aneuploidy?
1) Two normal gametes (each have 1 set of chromosomes)
2) One disomic gamete (2 sets of chromosomes instead of 1)
3) One nullosomic gamete (0 set of chromosomes instead of 1)
What is the most common trisomy among live born children?
1) Trisomy 21 - Down Syndrome
2) Frequency of about 1/600 to 1/1000 live births are down syndrome
What is the most common trisomy among live born children?
1) Trisomy 21 - Down Syndrome
2) Frequency of about 1/600 to 1/1000 live births are down syndrome
Autosomal monosomy results in ______
1) Underexpression of the genes on that chromosome
2) All prenatal lethals
Autosomal trisomy results in _______
1) Overexpression of the genes on that chromosome
2) Perinatal lethal except trisomy 21
Why do sex chromosomal trisomies have very mild if any phenotypic effects?
X-chromosome inactivation
What is Turner syndrome caused by?
A female is missing one of her two X chromosomes
What are indications that one should go for prenatal diagnosis of aneuploidy?
1) History of spontaneous abortion
2) Advanced maternal age (>35 years)
3) Family history of mental retardation/developmental delay
4) Fetal anomalies on ultrasound
What are indications for prenatal diagnosis of an aneuploidy?
1) History of spontaneous abortion
2) Advanced maternal age (>35 years)
3) Family history of mental retardation/developmental delay
4) Fetal anomalies on ultrasound
How is a Karyotype made and what can it be used for?
1) Amniocytes cultured for 7-10 days
2) Mitotic chromosomes are arrested at metaphase
3) Staining with Giemsa dye results in distinctive banding patterns (G-banding)
4) Aneuploidy (trisomy, monosomy), translocations, large duplications/deletions can be observed under the microscope
What is Fluorescence In Situ Hybridization (FISH)?
FISH is a cytogenetic technique that is used to detect and localize the presence or absence of specific DNA sequences on chromosomes
How does Fluorescence In Situ Hybridization (FISH) work?
1) FISH uses DNA probes tagged with fluorescent nucleotides that bind to only those parts of the chromosome with which they show a high degree of sequence complementarity
2) Fluorescence microscopy can be used to find out where the fluorescent probe is bound to the chromosomes
What is Fluorescence In Situ Hybridization (FISH) most commonly used for?
1) FISH is often used for finding specific features in DNA for use in genetic counseling, medicine, and species identification
a) Can be used to look for specific microdeletion or contiguous gene syndroms like Prader-Willi, Angelman or DiGeorge
b) Can be used to look carefully near the ends of chromosomes (subtelomeres) for a child with learning difficulties, mental retardation or autism
2) FISH can also be used to detect and localize specific RNA targets (mRNA, lncRNA and miRNA) in cells, circulating tumor cells, and tissue samples
a) Can be used to target oncogenes and tumor suppressor genes to identify amplified oncogenes or deleted tumor suppressor genes in tumors
What are advantages of Fluorescence In Situ Hybridization (FISH) over a Karyotype?
1) Rapid diagnosis relative to routine karyotype: FISH can be performed on interphase cells, so it does not require growth and metaphase arrest in cell culture
2) Can identify small, submicroscopic changes on chromosomes invisible to karyotyping as well as aneuploidies and large duplications/deletions (Prader-Willi, Angelman or DiGeorge)
What are advantages of Fluorescence In Situ Hybridization (FISH) over a Karyotype?
1) Rapid diagnosis relative to routine karyotype: FISH can be performed on interphase cells, so it does not require growth and metaphase arrest in cell culture
2) Can identify small, submicroscopic changes on chromosomes invisible to karyotyping as well as aneuploidies and large duplications/deletions
When is it helpful to use FISH on metaphase chromosomes rather than interphase chromosomes?
When looking for a particular deletion on a particular chromosome that may be small (DiGeorge)
Why is FISH important in breast cancer diagnosis?
1) FISH can determine how many copies of Her 2-neu genes (oncogenes) are overexpressed in an individual
2) 1/3 of women with breast cancer overexpress Her 2-neu genes
3) Herceptin can be prescribed to particularly target Her 2-neu and reduce overexpression
