1 / 50

Human Genetics

Human Genetics. Concepts and Applications Eighth Edition. Powerpoint Lecture Outline. Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley. Chapter 13 Chromosomes. Cytogenetics. A subdiscipline within genetics Focuses on chromosome variations

zephania-camacho
Download Presentation

Human Genetics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley

  2. Chapter 13Chromosomes

  3. Cytogenetics • A subdiscipline within genetics • Focuses on chromosome variations • Abnormal number of copies of genes or chromosomes can lead to genetic abnormalities • Human genome sequence information is used to identify genes that contribute to the chromosome-related syndromes

  4. Portrait of a Chromosome • Primarily DNA and protein • Described by size and shape • Heterochromatin (dark) • Euchromatin (light) • Contains: • Telomeres • Origin of replication sites • Centromere Figure 13.1

  5. Chromosomes • Heterochromatin is darkly staining, contains mostly repetitive DNA • Euchromatin contains more protein encoding genes • Telomeres are chromosome tips composed of many repeats of TTAGGG and shorten with each cell division • Centromere is the largest constriction of the chromosome and where spindle fibers attach

  6. Centromeres • Alpha satellite the bases that form the centromere are repeats of a 171-base DNA sequence • Centromere  associated proteins form the kinetochore that attaches to spindle fibers • Centromere protein A (CENP-A)  involved in centromere replication is passed to next generation and nearly identical in all species

  7. Subtelomeres • The chromosome region between the centromere and telomeres • Consists of 8,000  300,000 bases • Includes at least 500 protein-encoding genes • Near telomere the repeats similar to the telomere sequence • Multigene families that include pseudogenes

  8. Figure 13.2

  9. Karyotypes • Chromosomal chart • Chromosomes arranged by size and and structure • 24 types • Arranged by largest to smallest

  10. Centromere Position • At tip telocentric • Close to end  acrocentric • Displaced from center  submetacentric • At midpoint metacentric • Long arm q • Short arm p Figure 13.4

  11. Chromosomes Differ in Size Table 13.1

  12. Visualizing Chromosomes Obtain tissue from person Fetal tissue: amniocentesis chorionic villi sampling fetal cell sorting Adult tissue: blood (white blood cells) cheek swab (buccal cells) skin cells tissue biopsy Prepare cells on slide to remove cell matter Stain DNA with dyes or DNA probes to visualize DNA Evaluate chromosomes

  13. Amniocentesis Figure 13.5a

  14. Chorionic Villi Sampling Figure 13.5b

  15. Fetal Cell Sorting Figure 13.5c

  16. Karyotype • Metaphase chromosomes are squashed • Stained with DNA-binding dyes • Banding patterns help identify chromosomes Figure 13.8

  17. Table 13.2

  18. FISH • Fluorescence in situ hybridization • DNA probes labeled with fluorescing dye bind complementary DNA Figure 13.9

  19. Chromosomal Shorthand Table 13.3

  20. Chromosomal Shorthand • An ideogram represents a chromosome schematically. • The major banding regions are indicated with numbers. • Example • Sucrose intolerance is located at 3q.26 • or chromosome 3, long arm, major band 26) Figure 13.10

  21. The Normal Karyotype • Human somatic cells contain 46 chromosomes • 23 diploid chromosomes  paired homologs of chromosomes 1 to 22  sex chromosomes (XX or XY) • Diploid two sets of each chromosome. • Haploid gametes  one set of each chromosome • Euploid cells have a normal chromosome constitution

  22. Chromosome Abnormalities Table 13.4

  23. Polyploidy • 17% of all spontaneous abortions and 3% of stillbirths/newborn deaths show polyploidy Figure 13.11 • Triploid - three copies of each chromosome • Produced by • Two sperm fertilize one egg •  Haploid sperm fertilizes diploid egg

  24. Aneuploidy • Cells with extra or missing chromosomes • Nondisjunction is a common cause • Gametes produced with one 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

  25. Nondisjunction at Meiosis I Figure 13.12a

  26. Nondisjunction at Meiosis II Figure 13.12b

  27. Trisomies and Monosomies • Results in extra or missing copies of all of the genes on the chromosome • Most cease developing as embryos • Some fetuses with trisomy of smaller autosomes survive to birth Table 13.5

  28. Trisomy 21 • Down syndrome • Most common of trisomy • Distinctive facial and physical problems • Many medical problems are treatable • Varying degrees of developmental disabilities • Link with one form of Alzheimer disease • May also be produced by a translocation • Maternal age is a risk factor for having a child with Down syndrome

  29. Table 13.6

  30. Figure 13.7

  31. Trisomy 18 • Edward syndrome • Most due to nondisjunction in meiosis II in oocyte and do not survive • Serious medical and physical disabilities Figure 13.14a

  32. Trisomy 13 • Patau syndrome • Very rare and generally do not survive 6 months • Medical and physical abnormalities • Facial malformation and eye fusion

  33. Sex Chromosome Aneuploidy Table 13.7

  34. Turner Syndrome (45,X) • Only one copy of X chromosome • 1 in 2,500 female births • 99% of affected fetuses die in utero • Absence of Y leads to development as a female • Phenotypes include short stature, webbing at back of neck, incomplete sexual development (infertile), hearing impairment • Mosaics

  35. Triplo-X Aneuploidy (47, XXX) • 1 in 1,000 female births • Extra copy of every X-linked gene • Few modest effects on phenotype include tallness, menstrual irregularities, and slight impact on intelligence • X-inactivation of two X chromosomes occurs and cells have 2 Barr bodies • May compensate for presence of extra X

  36. Klinefelter Syndrome (47, XXY) • 1 in 1,000 male births • Extra copy of each X-linked gene • Phenotypes include • incomplete sexual development • rudimentary testes and prostate • long limbs, large hands and feet • some breast tissue development • Some cases are not diagnosed until fertility problems arise or remain undiagnosed

  37. XXYY Syndrome • Likely arises to unusual oocyte and sperm • AAD, obsessive compulsive disorder, learning disabilities, infertile • Treated with testosterone

  38. XYY Syndrome (47, XYY) • 1 in 1,000 male births • Extra Y chromosome • 96% phenotypically normal • Modest phenotypes may include • great height • acne and minor speech • reading disabilities • Studies suggesting increase in aggressive behaviors are not supported

  39. Chromosome Structural Abnormalities • Chromosomal deletions or duplications result in extra or missing copies of genes • Inversions alter the sequence of genes Figure 13.16

  40. A Duplication • Larger regions of deletion or duplication increase the likelihood that there will be an associated phenotype Figure 13.18

  41. Translocation • Nonhomologous chromosome exchange segments Two major types: • Robertsonian translocation • Two nonhomologous acrocentric chromosomes break at the centromere and long arms fuse. The short arms are often lost. • 5% of Down syndrome results from a Robertsonian translocation between chr 21 and chr 14. • Reciprocal translocation • Two nonhomologous chromosomes exchange a portion of their chromosome arms.

  42. Segregation of a Robertsonian Translocation Figure 13.19

  43. Reciprocal Translocation • Exchange of material from one chromosome arm to another • Some individuals carry a translocation but are not missing any genetic material unless a translocation breakpoint interrupts a gene Figure 13.20a

  44. Inversions • Inverted chromosomes have a region flipped in orientation • 5-10% cause health problems probably due to disruption of genes at the breakpoints • Inversions may impact meiotic segregation • Two types of inversions occur: • Paracentric • inverted region does NOT include centromere • Pericentric • inverted region includes centromere

  45. Segregation of a Paracentric Inversion Figure 13.21

  46. Segregation of a Pericentric Inversion Figure 13.22

  47. Isochromosomes • Chromosomes with identical arms • Form when centromeres divide along the incorrect plane during meiosis Figure 13.23

  48. Ring Chromosomes • Chromosomes shaped like a ring • Occur in 1 in 25,000 conceptions • May arise when telomeres are lost and sticky chromosome end fuse • Ring chromosomes have phenotypes associated with the loss or addition of genetic material

  49. Causes of Chromosomal Abnormalities Table 13.8

  50. Uniparental Disomy • Inheritance of two chromosomes from one parent • May occur • When nondisjunction occurs in both parents (a disomic gamete and one without homolog) • Loss or nondisjunction of one homolog in early embryo followed by reduplication of remaining homolog Figure 13.24

More Related