Human Genetics Concepts and Applications Fourteenth Edition PDF

Because learning changes everything.® Chapter 13 Chromosomes HUMAN GENETICS Concepts and Applications Fourteenth Edition Ricki Lewis © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Chromosomal Mutation...

Because learning changes everything.® Chapter 13 Chromosomes HUMAN GENETICS Concepts and Applications Fourteenth Edition Ricki Lewis © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Chromosomal Mutations Mutations large enough to be seen with a light microscope and/or fluorescent probes Missing, extra, or moved DNA Structural variants Large-scale chromosomal abnormalities present in all cells disrupt or halt prenatal development As a result, only 0.65% of all newborns have chromosomal anomalies that produce symptoms. Cytogenetics is the classical area of genetics that links chromosome variations to specific traits, including illnesses. © McGraw Hill 2  Portrait of a Chromosome 2 © McGraw Hill 3  Portrait of a Chromosome 3 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 © McGraw Hill 4  Telomere and Cancer Telomerase Labroots.com © McGraw Hill  Karyotype 1 A chromosome chart Major clinical tool Displays chromosomes arranged by size and structure Humans have 24 chromosome types Autosomes are numbered 1 to 22 by size Sex chromosomes are X and Y © McGraw Hill 6  Karyotype 2 Jens Goepfert/Shutterstock Access the text alternative for slide images. © McGraw Hill 7  Karyotype 3 Karyotypes are typically performed on cells during mitotic metaphase, when DNA coils tightly, enabling it to be visualized Karyotypes are useful at several levels They can: Confirm a clinical diagnosis Reveal effects of environmental toxins Clarify evolutionary relationships © McGraw Hill 8  Centromere Positions Telocentric—At the tip Acrocentric—Close to center Submetacentric—Off-center Metacentric—At center Access the text alternative for slide images. © McGraw Hill 9  Detecting Chromosomes Chromosomes can be imaged from any type of human cell that has a nucleus (RBCs do not). The most common application of human chromosome testing is in prenatal diagnosis. Chromosomes are also checked in relatives of people known to have atypical chromosomes, to explain infertility, or to diagnose or track cancers. Techniques Older approaches: amniocentesis and chorionic villus sampling (C V S) Newer approaches: Cell-Free Fetal DNA Testing © McGraw Hill 10  Amniocentesis A needle is used to remove a small sample of amniotic fluid from the uterus of a pregnant woman Ultrasound is used to follow needle’s movement Access the text alternative for slide images. © McGraw Hill 11  Chorionic Villus Sampling Performed during 10 to 12th week of pregnancy Provides earlier results than amniocentesis Does not detect metabolic problems Has greater risk of spontaneous abortion Access the text alternative for slide images. © McGraw Hill 12  The Maternal Age Effect For many years amniocentesis was limited to women over age 35, when the risk of the procedure equals the risk of miscarriage, which rises with maternal age Source: Color Atlas of Genetics by Eberhard Passage, p. 401. Thieme Medical Publishers, Inc. Access the text alternative for slide images. © McGraw Hill 13  The Maternal Age Effect 35 Percentage of clinically recognized pregnancies 30 Maternal age and trisomic conceptions 25 15 10 5 15 16 18 20 22 24 26 28 30 32 34 36 38 40 ≥42 Maternal age By age 42, about one in three identified pregnancies is trisomic. © McGraw Hill  Cell-Free Fetal DNA Testing 1 In a pregnant woman, about 20% of small DNA pieces found in the blood come from the placenta, and therefore represent the fetus Tests of cell-free fetal DNA are done at 10 weeks or later, and are rapidly replacing older techniques Called noninvasive prenatal diagnosis or testing. Analysis of cell-free fetal DNA is based on proportions. Entire genomes can be reconstructed from the DNA pieces. © McGraw Hill 15  Cell-Free Fetal DNA Testing 2 Noninvasive method Dennis Lo Breakthrough Awardee, 2021 https://www.cnn.com/2016/03/24/health © McGraw Hill  Chromosomal Shorthand 1 a way to succinctly describe the structure, number, and any abnormalities of chromosomes in a karyotype or genetic analysis. Symbols and shorthand describe the type of aberration After the shorthand, numbers correspond to bands and subbands A chromosomally normal male is designated 46,XY and a female 46,XX. Bands and subbands identify specific genes. © McGraw Hill 17  Chromosomal Shorthand 2 Table 13.1 Chromosomal Shorthand Abbreviation Meaning 46,XY Chromosomal male 46,XX Chromosomal female 45,X A female with one X 47,XXY A male with an extra X 47,XYY A male with an extra Y 46,XY,del (7q) A male missing part of the long arm of chromosome 7 47,XX,+21 A female with trisomy 21 Down syndrome 46,XY,t(7;9)(p21.1; q34.1) A male with a translocation between the short arm of chromosome 7 at band 21.1 and the long arm of chromosome 9 at band 34.1 48,XXYY A male with an extra X and an extra Y chromosome © McGraw Hill 18  Atypical Chromosomes 1 Karyotype may be atypical (abnormal) in: Chromosome number Chromosome structure Atypical chromosomes account for at least 50% of spontaneous abortions, yet only 0.65% of newborns have them. Therefore, most embryos and fetuses with atypical chromosomes stop developing before birth. © McGraw Hill 19  Atypical Chromosomes 2 Table 13.2 Atypical Chromosomes Chromosome Variant Description Polyploidy Extra chromosome sets Aneuploidy An extra or missing chromosome Monosomy One chromosome absent Trisomy One chromosome extra Deletion Part of a chromosome missing Duplication Part of a chromosome present twice Translocation Two chromosomes join long arms or exchange parts Inversion Segment of chromosome reversed Isochromosome A chromosome with identical arms Ring chromosome A chromosome that forms a ring due to deletions in telomeres, which cause ends to adhere Chromothripsis One or more chromosomes shatters © McGraw Hill 20  Variations in Chromosome Number Changes in chromosome number can cause genetic disorders Euploidy One or more than one complete set of chromosomes (can be normal or abnormal) Polyploidy An increase in the number of chromosome sets (abnormal) Aneuploidy Changes in chromosome numbers involving less than the duplication of a whole chromosome set (abnormal) Often, the gain or loss of a single chromosome Monosomy (2n-1) Trisomy (2n+1) © McGraw Hill  Polyploidy Cell with extra chromosome sets Triploid (3N) cells have three sets of chromosomes Produced by: Fertilization of one egg by two sperm (69, XYY, most common) Fusion of haploid and diploid gametes Account for 17% of all spontaneous abortions 1 in 10,000 live births, but usually fatal within a month © McGraw Hill 22  Triploidy CNRI/Science Source Access the text alternative for slide images. © McGraw Hill 23  Aneuploidy Aneuploidy is most often due to nondisjunction during meiosis Autosomal monosomy Rarely observed in miscarriages or live births Most likely lethal before the pregnancy is recognized Autosomal trisomy Accounts for 50% of the chromosomal abnormalities observed in miscarriages Only a few autosomal trisomies result in live birth Trisomy 13, trisomy 18, trisomy 21 Trisomy 21 is the only trisomy that allows survival to adulthood © McGraw Hill 24  Nondisjunction A type of chromosomal error that occurs when chromosomes fail to separate properly during cell division. Produces gamete with an extra chromosome and another with one missing chromosome Nondisjunction during meiosis I results in copies of both homologs in one secondary oocyte/spermatocyte (and none in the other) Nondisjunction during meiosis II results in both sister chromatids in one gamete (and none in the other) © McGraw Hill 25  Nondisjunction at Meiosis I Abnormal separation of Extra chromosome homologous chromosomes (n + 1) Nondisjunction Extra chromosome (n + 1) Missing chromosome (n − 1) Missing chromosome (n − 1) Meiosis I Meiosis II Gametes © McGraw Hill 26  Nondisjunction at Meiosis II Abnormal separation of sister chromatids Nondisjunction Normal division Extra chromosome (n + 1) Missing chromosome (n − 1) Normal (n) Normal (n) Meiosis I Meiosis II Gametes © McGraw Hill 27  Autosomal Aneuploids Most autosomal aneuploids cease developing long before birth Frequently seen trisomies in newborns are those of chromosomes 21, 18, and 13. Carry fewer genes than other autosomes Table 13.3 Comparing and Contrasting Trisomies 13, 18, and 21 Type of Trisomy Incidence at Birth Percent Survival 1 Year After Birth 13 (Patau) 1 ⁄ 12,500–1 ⁄ 21,700