Chapter 2

Genes and Genetic Diseases

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 DNA

 Deoxyribose
 Phosphate molecule
 Four nitrogenous bases:
 Pyrimidines: cytosine and thymine
 Purines: adenine and guanine
 Double helix model
 Nucleotide

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 Proteins

 One or more polypeptides

 Composed of amino acids
 Twenty amino acids
 Directed by sequence of bases (codons)

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 DNA Replication

 Untwisting and unzipping of the DNA strand

 Single strand acts as a template
 Complementary base pairing by DNA
polymerase
 Adenine-thymine; cytosine-guanine

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 Mutation

 Any inherited alteration of genetic material

 Chromosome—aberrations
 Base pair substitution
 One base pair is substituted for another
 Frameshift mutation
 Insertion or deletion of one or more base pairs
 Causes a change in the entire “reading frame”

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 Mutation (Cont.)

 Spontaneous mutation
 Mutation that occurs in absence of exposure to
known mutagens
 Mutational hot spots
 Areas of the chromosomes that have high
mutation rates

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 Mutagen

 Agent known to increase the frequency of

mutations
 Radiation
 Chemicals
• Nitrogen mustard, vinyl chloride, alkylating agents,
formaldehyde, sodium nitrite

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 Transcription

 RNA is synthesized from the DNA template

 RNA polymerase binds to promoter site
 Results in the formation of messenger RNA
(mRNA)
 RNA polymerase detaches
 mRNA moves out of the nucleus and into the
cytoplasm
 Transcription continues until termination
sequence is reached
https://www.youtube.com/watch?v=gG7uCskUOrA
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 Gene Splicing

 Many RNA sequences are removed (introns),

and those remaining are spliced together
(exons) before mRNA migrates to the
cytoplasm
 is a post-transcriptional modification in which
a single gene can code for multiple proteins
 is an important source of protein diversity

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 Translation

 Process by which RNA directs the synthesis

of a polypeptide via interaction with tRNA
 Site of protein synthesis is the ribosome
 tRNA contains a sequence of nucleotides
(anticodon) complementary to the triad of
nucleotides on the mRNA strand (codon)

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 Translation (Cont.)

 The ribosome moves along the mRNA

sequence to translate the amino acid
sequence
 Continues until termination sequence is
reached
 Then polypeptide is released into cytoplasm

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1. Which of the following statements is TRUE?

A. RNA is double stranded.

B. DNA is replicated in the cytoplasm.
C. RNA contains the same bases as DNA.
D. A mutation is an inherited alteration of DNA.

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 Chromosomes

 Somatic cells
 Contain 46 chromosomes (23 pairs)
 Diploid cells

 Gametes
 Contain 23 chromosomes
 Haploid cells
• One member of each chromosome pair

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 Chromosomes (Cont.)

 Meiosis
 Formation of haploid cells from diploid cells
 Mitosis
 Formation of somatic cells

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 Chromosomes (Cont.)

 Autosomes
 The first 22 of the 23 pairs of chromosomes in
males and females
 The two members are virtually identical and thus
said to be homologous
 Sex chromosomes
 Remaining pair of chromosomes
• In females, it is a homologous pair (XX)
• In males, it is a nonhomologous pair (XY)
 Karyotype (karyogram)

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 Karyotype

 Ordered display of chromosomes

From Raven PH et al: Biology, ed 8, New York, 2008, McGraw-Hill.

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 Chromosome Aberrations

 Euploid cells have a multiple of the normal

number of chromosomes
 Haploid and diploid cells are euploid forms
 When a euploid cell has more than the diploid
number, it is called a polyploid cell
• Triploidy: a zygote having three copies of each
chromosome (69 total)
• Tetraploidy: four copies of each (92 total)
 Neither triploid nor tetraploid fetuses survive

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 Chromosome Aberrations (Cont.)

 Aneuploidy
 A somatic cell that does not contain a multiple of
23 chromosomes
 A cell containing three copies of one chromosome
is trisomic (trisomy)
 Monosomy is the presence of only one copy of
any chromosome
 Monosomy is lethal, but infants can survive with
trisomy of certain chromosomes
 It is better to have extra than less

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 Chromosome Aberrations (Cont.)

 Nondisjunction
 Usually the cause of aneuploidy
 Failure of homologous chromosomes or sister
chromatids to separate normally during meiosis or
mitosis

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 Nondisjunction

From Jorde LB et al: Medical genetics, ed 4, St Louis, 2010, Mosby.

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 Autosomal Aneuploidy

 Partial trisomy
 Only an extra portion of a chromosome is present
in each cell
 Chromosomal mosaics
 Trisomies occurring only in some cells of the body

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 Autosomal Aneuploidy (Cont.)

 Down syndrome
 Best known example of aneuploidy
• Trisomy 21
 1:800 live births
 Mentally challenged, low nasal bridge, epicanthal
folds, protruding tongue, low-set ears, poor
muscle tone
 Risk increases with maternal age above 35

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 Down Syndrome

Courtesy Drs. A. Olney and M. MacDonald, University of Nebraska Medical Center, Omaha, Neb.

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 Sex Chromosome Aneuploidy

 One of the most common is trisomy X (a

female who has three X chromosomes)
 Symptoms are variable: sterility, menstrual
irregularity, and/or intellectual disability
 Symptoms worsen with each additional X

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Sex Chromosome Aneuploidy (Cont.)

 Turner syndrome
 Females with only one X chromosome
 Characteristics:
• Underdeveloped ovaries (sterile)
• Short stature (~ 4'7")
• Webbing of the neck
• Edema
• Underdeveloped breasts; wide nipples
• High number of aborted fetuses
 X is usually inherited from mother

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 Turner Syndrome Karyotype

From Patton KT, Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby. Courtesy Nancy S. Wexler, PhD,
Columbia University.

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 Sex Chromosome Aneuploidy

 Klinefelter syndrome
 Individuals with at least two Xs and one Y
chromosome
 Characteristics
• Male appearance
• Develop female-like breasts
• Small testes—usually sterile
• Sparse body hair
• Long limbs

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Sex Chromosome Aneuploidy (Cont.)

 Klinefelter syndrome (Cont.)

 Some individuals can be XXY and XXXY
 The abnormalities increase with each X

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 Klinefelter Syndrome

From Patton KT, Thibodeau GA: Anatomy & physiology, ed 9, St Louis, 2016, Mosby. Courtesy Nancy S. Wexler,
PhD, Columbia University.

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