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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Genetics Brochure Info: • Due Date March 5th • Follow the guidelines on the rubric 13-1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. March of Dimes Info • • • • Hello! Starting on Monday, all Genetics students, (past, present and future) may register for the March for Babies! Remember that this year the March for Babies has a focus on helping children who were born prematurely. Most of us know and love some who had a premature birth, and we want the best life possible for them and for all babies. JOIN OUR WALK! • • Go to our team website and sign up. http://www.marchforbabies.org/team/t1379641 • You may also DONATE ONLINE! • • Please also come to Room 720 and sign our MARCH FOR BABIES WALL. You can pick up a walker envelope and a coin bucket if you like. • Plan to arrive at Marietta Middle School at 8:00 AM April 24 for our group photo. The walk begins at 8:30 and will be about 3 miles long through Marietta neighborhoods. March for Babies will provide some breakfast and lunch treats. • IT IS STILL NOT TOO LATE TO DESIGN A MARCH FOR BABIES T-SHIRT! • Come sign up in Room 720!!! 13-2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 13 Chromosomes 13-3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Portrait of a Chromosome • Primarily DNA and protein • Described by size and shape • Heterochromatin (dark) • Euchromatin (light) • Contains: Figure 13.1 – Telomeres – Origin of replication sites – Centromere 13-5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-6 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-7 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-8 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 13.2 13-9 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Karyotypes • Chromosomal chart • Chromosomes arranged by size and and structure • 24 types • Arranged by largest to smallest 13-10 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromosomes Differ in Size Table 13.1 13-12 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-13 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Amniocentesis Figure 13.5a 13-14 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chorionic Villi Sampling Figure 13.5b 13-15 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fetal Cell Sorting Figure 13.5c 13-16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Karyotype • Metaphase chromosomes are squashed • Stained with DNA-binding dyes • Banding patterns help identify chromosomes 13-17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Table 13.2 13-18 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. FISH • Fluorescence in situ hybridization • DNA probes labeled with fluorescing dye bind complementary DNA Figure 13.9 13-19 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromosomal Shorthand Table 13.3 13-20 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-21 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-22 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromosome Abnormalities Table 13.4 13-23 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-24 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 13-25 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-26 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nondisjunction at Meiosis I Figure 13.12a 13-27 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nondisjunction at Meiosis II Figure 13.12b 13-28 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-29 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-30 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Table 13.6 13-31 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 13.7 13-32 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-33 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Trisomy 13 • Patau syndrome • Very rare and generally do not survive 6 months • Medical and physical abnormalities • Facial malformation and eye fusion 13-34 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sex Chromosome Aneuploidy Table 13.7 13-35 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-36 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-37 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-38 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. XXYY Syndrome • Likely arises to unusual oocyte and sperm • AAD, obsessive compulsive disorder, learning disabilities, infertile • Treated with testosterone 13-39 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-40 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromosome Structural Abnormalities Figure 13.16 • Chromosomal deletions or duplications result in extra or missing copies of genes • Inversions alter the sequence of genes 13-41 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. A Duplication Figure 13.18 • Larger regions of deletion or duplication increase the likelihood that there will be an associated phenotype 13-42 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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. 13-43 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Segregation of a Robertsonian Translocation Figure 13.19 13-44 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-45 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-46 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Segregation of a Paracentric Inversion Figure 13.21 13-47 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Segregation of a Pericentric Inversion Figure 13.22 13-48 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Isochromosomes • Chromosomes with identical arms • Form when centromeres divide along the incorrect plane during meiosis Figure 13.23 13-49 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 13-50 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Causes of Chromosomal Abnormalities Table 13.8 13-51 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Uniparental Disomy Figure 13.24 • 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 13-52