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Concepts of genetics 12th edition

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CHAPTER CONCEPTS ■ ■ The failure of chromosomes to properly separate during meiosis results in variation in the chromosome content of gametes and subsequently in offspring arising from such gametes. ■ ■ Plants often tolerate an abnormal genetic content, but, as a result, they often manifest unique phenotypes. Such genetic variation has been an important factor in the evolution of plants. ■ ■ In animals, genetic information is in a delicate equilibrium whereby the gain or loss of a chromosome, or part of a chromosome, in an otherwise diploid organism often leads to lethality or to an abnormal phenotype. ■ ■ The rearrangement of genetic information within the genome of a diploid organism may be tolerated by that organism but may affect the viability of gametes and the phenotypes of organisms arising from those gametes. ■ ■ Chromosomes in humans contain fragile sites—regions susceptible to breakage, which lead to abnormal phenotypes. In previous chapters, we have emphasized how mutations and the resulting alleles affect an organism’s phenotype and how traits are passed from parents to offspring according to Mendelian principles. In this chapter, we look at phenotypic variation that results from Spectral karyotyping of human chromosomes, utilizing differentially labeled “painting” probes. more substantial changes than alterations of individual genes—modifications at the level of the chromosome. Although most members of diploid species normally contain precisely two haploid chromosome sets, many known cases vary from this pattern. Modifications include a change in the total number of chromosomes, the deletion or duplication of genes or segments of a chromosome, and rearrangements of the genetic material either within or among chromosomes. Taken together, such changes are called chromosome mutations or chromosome aberrations, to distinguish them from gene mutations. Because the chromosome is the unit of genetic transmission, according to Mendelian laws, chromosome aberrations are passed to offspring in a predictable manner, resulting in many unique genetic outcomes. Because the genetic component of an organism is delicately balanced, even minor alterations of either content or location of genetic information within the genome can result in some form of phenotypic variation. More substantial changes may be lethal, particularly in animals. Throughout this chapter, we consider many types of chromosomal aberrations, the phenotypic consequences for the organism that harbors an aberration, and the impact of the aberration on the offspring of an affected individual. We will also discuss the role of chromosomal aberrations in the evolutionary process. 171GENES, CHROMOSOMES, AND HEREDITY 172 PART 1 8.1   Variation in Chromosome Number: Terminology and Origin Variation in chromosome number ranges from the addition or loss of one or more chromosomes to the addition of one or more haploid sets of chromosomes. Before we embark on our discussion, it is useful to clarify the terminology that describes such changes. In the general condition known as aneuploidy, an organism gains or loses one or more chromosomes but not a complete set. The loss of a single chromosome from an otherwise diploid genome is called monosomy. The gain of one chromosome results in trisomy. These changes are contrasted with the condition of euploidy, where complete haploid sets of chromosomes are present. If more than two sets are present, the term polyploidy applies. Organisms with three sets are specifically triploid, those with four sets are tetraploid, and so on. Table 8.1 provides an organizational framework for you to follow as we discuss each of these categories of aneuploid and euploid variation and the subsets within them. As we consider cases that include the gain or loss of chromosomes, it is useful to examine how such aberrations originate. For instance, how do the syndromes arise where the number of sex-determining chromosomes in humans is altered (Chapter 7)? As you may recall, the gain (47,XXY) or loss (45,X) of an X chromosome from an otherwise diploid genome affects the phenotype, resulting in Klinefelter syndrome or Turner syndrome, respectively (see Figure 7.2). Human females may contain extra X chromosomes (e.g., 47,XXX, 48,XXXX), and some males contain an extra Y chromosome (47,XYY). Such chromosomal variation originates as a random error during the production of gametes, a phenomenon referred to as nondisjunction, whereby paired homologs TABLE 8.1 Terminology for Variation in Chromosome Numbers Term Aneuploidy Monosomy Disomy Trisomy Tetrasomy, pentasomy, etc. Euploidy Diploidy Polyploidy Triploidy Explanation 2n { x chromosomes 2n- 1 2n 2n + 1 2n + 2, 2n + 3, etc. Multiples of n 2n 3n, 4n, 5n, . . . 3n Tetraploidy, pentaploidy, etc. 4n, 5n, etc. Autopolyploidy Multiples of the same genome Allopolyploidy (amphidiploidy) Multiples of closely related genomes NOW SOLVE THIS 8.1 A human female with Turner syndrome (47,X) also expresses the X-linked trait hemophilia, as did her father. Which of her parents underwent nondisjunction during meiosis, giving rise to the gamete responsible for the

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, Brief Contents

PA RT ON E PART FOUR
G EN E S , C H R O MOS OME S , AND GENETIC TECHNOLOGY AND
H ERE D IT Y GENOM ICS
1 Introduction to Genetics 1 20 Recombinant DNA Technology 454

2 Mitosis and Meiosis 14 21 Genomic Analysis 485

3 Mendelian Genetics 36 22 Applications of Genetic Engineering and
4 Extensions of Mendelian Genetics 62 Biotechnology 521

5 Chromosome Mapping in Eukaryotes 94

6 Genetic Analysis and Mapping in Bacteria and PART FIVE
Bacteriophages 123
GENETIC ANALYSIS OF ORGA NISM S
7 Sex Determination and Sex Chromosomes 151 AND POPULATIONS
8 Chromosomal Mutations: Variation in Number
and Arrangement 171 23 Developmental Genetics 555

9 Extranuclear Inheritance 196 24 Cancer Genetics 579

25 Quantitative Genetics and Multifactorial
Traits 599
PA RT TWO 26 Population and Evolutionary Genetics 621
D N A : ST R U C T UR E , R E P LIC ATION,
A N D O R G A N IZ AT ION
SPECIAL TOPICS IN M OD E RN
10 DNA Structure and Analysis 213
GENETICS
11 DNA Replication and Recombination 238
1 CRISPR-Cas and Genome Editing 649
12 DNA Organization in Chromosomes 263
2 DNA Forensics 661

3 Genomics and Precision Medicine 672
PA RT T HR E E
4 Genetically Modified Foods 683
G EN E E X P R E S S IO N A ND IT S 5 Gene Therapy 695
R EG U L AT I O N
6 Advances in Neurogenetics: The Study of
13 The Genetic Code and Transcription 283 Huntington Disease 710
14 Translation and Proteins 312

15 Gene Mutation, DNA Repair, and Appendix A Selected Readings A-1
Transposition 340
Appendix B Answers to Selected Problems B-1
16 Regulation of Gene Expression in Bacteria 373
Glossary G-1
17 Transcriptional Regulation in Eukaryotes 393
Credits C-1
18 Posttranscriptional Regulation in
Eukaryotes 413 Index I-1

19 Epigenetic Regulation of Gene Expression 433




CVR_KLUG4718_12_SE_BEP.indd 2-3

,Nobel Prizes Awarded for Research in Genetics or Genetics-Related Areas
Year Recipients Nobel Prize Discovery/Research Topic
2017 J. C. Hall Physiology or Identification of the genes and molecular mechanisms
M. Rosbash Medicine that regulate circadian rhythms
M. W. Young
2015 T. Lindahl Chemistry Mechanistic studies of DNA repair
P. Modrich
A. Sancar
2012 J. B. Gurdon Physiology or Differentiated cells can be reprogrammed to become
S. Yamanaka Medicine pluripotent
2009 V. Ramakrishnan Chemistry Structure and function of the ribosome
T. A. Steitz
A. E. Yonath
2009 E. H. Blackburn Physiology or The nature and replication of the DNA of telomeres,
C. W. Greider Medicine and the discovery of the telomere-replenishing ribonu-
J. W. Szostak cleoprotein enzyme telomerase
2008 O. Shimomura Chemistry Discovery and development of a genetically encoded
M. Chalfie fluorescent protein as an in vivo marker of gene
R. Y. Tsien expression
2007 M. R. Capecchi Physiology or Gene-targeting technology essential to the creation
M. J. Evans Medicine of knockout mice serving as animal models of human
O. Smithies disease
2006 R. D. Kornberg Chemistry Molecular basis of eukaryotic transcription
2006 A. Z. Fire Physiology or Gene silencing using RNA interference (RNAi)
C. C. Mello Medicine
2004 A. Ciechanover Chemistry Regulation of protein degradation by the proteasome
A. Hershko
I. Rose
2002 S. Brenner Physiology or Genetic regulation of organ development and pro-
H. R. Horvitz Medicine grammed cell death (apoptosis)
J. E. Sulston
2001 L. H. Hartwell Physiology or Genes and regulatory molecules controlling the cell
T. Hunt Medicine cycle
P. M. Nurse
1999 G. Blobel Physiology or Genetically encoded amino acid sequences in proteins
Medicine that guide their cellular transport
1997 S. B. Prusiner Physiology or Prions—a new biological principle of infection
Medicine
1995 E. B. Lewis Physiology or Genetic control of early development in Drosophila
C. NÜsslein-Volhard Medicine
E. Wieschaus
1993 R. J. Roberts Physiology or RNA processing of split genes
P. A. Sharp Medicine
K. B. Mullis Chemistry Development of polymerase chain reaction (PCR) and
M. Smith site-directed mutagenesis (SDM)
1989 J. M. Bishop Physiology or Role of retroviruses and oncogenes in cancer
H. E. Varmus Medicine
T. R. Cech Chemistry Ribozyme function during RNA splicing
S. Altman
1987 S. Tonegawa Physiology or Genetic basis of antibody diversity
Medicine




12/1/17 1:02 P

, Year Recipients Nobel Prize Discovery/Research Topic
1985 M. S. Brown Physiology or Genetic regulation of cholesterol metabolism
J. L. Goldstein Medicine
1983 B. McClintock Physiology or Mobile genetic elements in maize
Medicine
1982 A. Klug Chemistry Crystalline structure analysis of significant complexes,
including tRNA and nucleosomes
1980 P. Berg Chemistry Development of recombinant DNA and DNA sequenc-
W. Gilbert ing technology
F. Sanger
1978 W. Arber Physiology or Recombinant DNA technology using restriction endo-
D. Nathans Medicine nuclease technology
H. O. Smith
1976 B. S. Blumberg Physiology or Elucidation of the human prion-based diseases, kuru
D. C. Gajdusek Medicine and Creutzfeldt-Jakob disease
1975 D. Baltimore Physiology or Molecular genetics of tumor viruses
R. Dulbecco Medicine
H. M. Temin
1972 G. M. Edelman Physiology or Chemical structure of immunoglobulins
R. R. Porter Medicine
C. B. Anfinsen Chemistry Relationship between primary and tertiary structure
of proteins
1970 N. Borlaug Peace Prize Genetic improvement of Mexican wheat
1969 M. Delbrück Physiology or Replication mechanisms and genetic structure of
A. D. Hershey Medicine bacteriophages
S. E. Luria
1968 H. G. Khorana Physiology or For their interpretation of the genetic code and its
M. W. Nirenberg Medicine function during protein synthesis
R. W. Holley
1966 P. F. Rous Physiology or Viral induction of cancer in chickens
Medicine
1965 F. Jacob Physiology or Genetic regulation of enzyme synthesis in bacteria
A. M. Lwoff Medicine
J. L. Monod
1962 F. H. C. Crick Physiology or Double helical model of DNA
J. D. Watson Medicine
M. H. F. Wilkins
J. C. Kendrew Chemistry Three-dimensional structure of globular proteins
M. F. Perutz
1959 A. Kornberg Physiology or Biological synthesis of DNA and RNA
S. Ochoa Medicine
1958 G. W. Beadle Physiology or Genetic control of biochemical processes
E. L. Tatum Medicine
J. Lederberg Physiology or Genetic recombination in bacteria
Medicine
F. Sanger Chemistry Primary structure of proteins
1954 L. C. Pauling Chemistry Alpha helical structure of proteins
1946 H. J. MÜller Physiology or X-ray induction of mutations in Drosophila
Medicine
1933 T. H. Morgan Physiology or Chromosomal theory of inheritance
Medicine
1930 K. Landsteiner Physiology or Discovery of human blood groups
Medicine




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