Chromosomes, Karyotyping, and Abnormalities (Learning Objectives) Learn the components and parts of a metaphase chromosome.
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1 Chromosomes, Karyotyping, and Abnormalities (Learning Objectives) Learn the components and parts of a metaphase chromosome. Define the terms karyotype, autosomal and sex chromosomes. Explain how many of each is present in a gamete and in a somatic cell. Explain the field of cytogenetics and its uses for visualization of chromosomes, karyotyping for prenatal and postnatal diagnoses, including the sources of cells used. Explain the differences between the three prenatal diagnosis techniques. Learn the terms used to describe the abnormalities in chromosomal numbers: polyploidy, aneuploidy: trisomy and monosomy, and mosiacism and their causing mechanisms. Learn the terms that describe the abnormalities in chromosomal structure: deletions, duplications, translocations, and inversions. Learn the basics of the shorthand used to describe normal and abnormal karyotypes. Recognize the common autosomal and sex chromosome aneuploidies. 1
2 Portrait of a Chromosome Figure
3 Portrait of a Chromosome A chromosome consists primarily of DNA and protein Chromosome differ in size and shape Essential parts are: - Telomeres - Origins of replication sites - Centromere 3
4 Portrait of a Chromosome Heterochromatin is darkly staining - Consists mostly of repetitive DNA Euchromatin is lighter-staining - Contains most protein-encoding genes Telomeres are chromosome tips composed of many repeats of TTAGGG - Shorten with each cell division 4
5 Centromeres The largest constriction of the chromosomeattachment sites of spindle fibers DNA present at the centromere are specific repeated sequence 5
6 Subtelomeres The region between the centromere and telomeres Consists of 8,000 to 300,000 bases Near telomere the repeats are similar to the telomere sequence 6
7 Subtelomeres Figure 13.2 Figure
8 Viewing Chromosomes 1882 Figure 13.8 Now Drawing by German biologist Walther Flemming Micrograph of actual stained human chromosomes 8
9 Cytogenetics Variations in chromosomal structure occur as cells go through the cell cycle Cytogenetics is a technical field within genetics for visualization of chromosomal variations Excess genetic material has milder effects on health than a deficit Most large-scale chromosomal abnormalities disrupt or halt prenatal development 9
10 Karyotype A visual display of metaphase chromosomes arranged by size and structure The chromosome pairs 1 trough 22 are autosome These are sex chromosomes 10
11 Karyotype A visual display of chromosomes arranged by size and structure - Autosomes are numbered 1-22 by size - Sex chromosomes are X and Y Humans have 24 different chromosome types 11
12 Figure
13 Centromere Positions Position of centromeres varies between chromosomes At tip Telocentric Close to end Acrocentric Off-center Submetacentric At midpoint Metacentric Figure
14 Karyotype are useful 1) Can confirm a clinical diagnosis 2) Can reveal effects of environmental toxins 3) Can clarify evolutionary relationships 14
15 Sources used for Karyotyping Tissue is obtained from person - Fetal tissue: Amniocentesis Chorionic villi sampling Fetal cell sorting Chromosome microarray analysis - Adult tissue: White blood cells Skin-like cells from cheek swab Chromosomes are extracted Then stained with a combination of dyes and DNA probes 15
16 Prenatal Diagnosis: Amniocentesis Detects about 1,000 of the more than 5,000 known chromosomal and biochemical problems Ultrasound is used to follow needle s movement Figure 13.5a Figure
17 Prenatal Diagnosis: Chorionic Villi Sampling Performed during th week of pregnancy Provides earlier results than amniocentesis Limited detection of some metabolic problems Has greater risk of spontaneous abortion Figure 13.5b 17
18 Prenatal Diagnosis: Fetal Cell Sorting Fetal cells are distinguished from maternal cells by a fluorescence-activated cell sorter - Identifies cell-surface markers A new technique detects fetal mrna in the bloodstream of the mother Figure 13.5c 18
19 FISH Fluorescence in situ hybridization DNA probes labeled with fluorescing dye bind complementary DNA Fluorescent dots correspond to three copies of chromosome 21 Figure
20 Chromosome Abnormalities A karyotype may be abnormal in two ways: 1) In chromosome number 2) In chromosome structure Abnormal chromosomes account for at least 50% of spontaneous abortions Due to improved technology, more people are being diagnosed with chromosomal abnormalities 20
21 Table
22 22
23 Polyploidy Cell with extra set of chromosomes is polyploid Triploid (3N) cells have three sets of chromosomes - Produced in one of two main ways: o o Fertilization of one egg by two sperm Fusion of haploid and diploid gametes Triploids account for 17% of all spontaneous abortions and 3% of stillbirths and newborn deaths 23
24 Triploidy Figure
25 Aneuploidy A normal chromosomal number is euploid Cells with extra or missing chromosomes are aneuploid, i.e. gain or loss of a single chromosome Most autosomal aneuploids are spontaneously aborted Those that are born are more likely to have an extra chromosome (trisomy) rather than a missing one (monosomy) 25
26 Nondisjunction The failure of chromosomes to separate normally during meiosis Produces gamete with an extra chromosome and another with one missing chromosome Nondisjunction during Meiosis I results in copies of both homologs in one gamete Nondisjunction during Meiosis II results in both sister chromatids in one gamete 26
27 Nondisjunction at Meiosis I Figure
28 Nondisjunction at Meiosis II Figure
29 Aneuploidy Aneuploidy can also arise during mitosis after the zygote formation, producing groups of somatic cells with the extra or missing chromosomes autosomal aneuploidy sex chromosome aneuploidy An individual with two chromosomally-distinct cell populations is called a mosaic A mitotic non-disjunction event that occurs early in development can have serious effects on the health of the individual 29
30 AutosomalTrisomies Most autosomal aneuploids cease developing as embryos or fetuses Most frequently seen trisomies in newborns are those of chromosomes 21, 18, and 13 - Carry fewer genes than other autosomes 30
31 Table
32 Sex Chromosome Aneuploidy Missing one or having one or more additional copies the sex chromosomes Turner syndrome Triplo-X Klinefelter Syndrome XXYY Syndrome XYY Syndrome 32
33 Chromosome Structural Abnormalities _view0/chapter13/changes_in_chr omosome_structure.html Figure
34 Chromosomal Structural Abnormalities Deletions o missing a segment from a chromosome Duplications o Presence of an extra segment on a chromosome (Deletions and duplications often not inherited, arise de novo) Translocations o o two non-homologous chromosomes exchange segments Balanced and unbalanced translocations Inversions o A chromosomal segment is flipped in orientation 34
35 Chromosomal Shorthand 35
36 Duplications in Chromosome 15 Figure
37 Figure Figure
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