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Because learning changes everything.(R) Chapter 13 Mutations and Genetic Testing Essentials of Biology SEVENTH EDITION Sylvia S. Mader Michael Windelspecht (C) McGraw Hill LLC.Rheumatoid arthritis o Immune system destroys person's own body o Inject adenoviruses that contain anti-inflammatory genes into the affected joint (C) McGraw Hill LLC 2Figure 13.10 Use of a DNA Microarray to Test for Mutated Genes (C) McGraw Hill LLC 18 DNA Sequencing o Individual's complete genome o Important in personalized medicine o Can not only show risk for disease but also holds key to new treatment options o Based on genetic information, it is possible to improve patient outcomes and increase treatment options with increased precision o Becoming more affordable leading to popularity of personalized medicine (C) McGraw Hill LLC 19 Testing the Fetus Ultrasound--helps evaluate fetal anatomy for serious abnormalities o Uses high-frequency sound waves Testing fetal cells o Cells from amniocentesis or chorionic villus sampling o Fetal cells can also be collected from mother's blood o PCR used to amplify DNA, no risk to fetus (C) McGraw Hill LLC 20 Testing the Embryo o Testing the embryo-- following IVF, one cell can be removed from embryo without harm Access the text alternative for slide images.Inv dup 15 syndrome--inverted duplication of chromosome 15 o Inversion--segment joins in direction opposite from normal (C) McGraw Hill LLC 9 Chromosomal Mutations- Translocation Rearrangement of parts between nonhomologous chromosomes.o Alignment only possible when the inverted chromosome forms a loop (C) McGraw Hill LLC 12 Genetic Testing Genetic counseling--potential parents are advised on their risk of inherited disorders Counselor helps couple understand the mode of inheritance, medical consequences of disorder, and decisions they might wish to make Karyotyping--visual display of chromosomes arranged by size, shape, and banding pattern.(C) McGraw Hill LLC Kateryna Kon/Shutterstock 15 Testing for a Protein Some disorders are caused by a missing enzyme o Test for quantity of enzyme produced (C) McGraw Hill LLC 16 Testing the DNA- Genetic Markers Relies on an abnormality in the DNA sequence due to presence of abnormal allele.(C) McGraw Hill LLC 25 In Vivo Gene Therapy Cystic fibrosis treatment o Gene needed is sprayed into the nose or delivered to lower respiratory tract o Use adenoviruses or liposomes to carry gene Poor coronary circulation treatment o Vascular endothelial growth factor can cause growth of new blood vessels.(C) McGraw Hill LLC 23 Ex Vivo Gene Therapy Treatment of SCID o Severe combined immunodeficiency o Lack enzyme involved in the maturation of cells producing antibodies o Bone marrow stem cells are removed and infected with RNA retrovirus carrying the gene for normal enzyme.o Williams syndrome--chromosome 7 loses a tiny end piece o Cri du chat--chromosome 5 loses an end piece (C) McGraw Hill LLC 8 Chromosomal Mutations- Duplication Chromosome segments are repeated Individual has more than two alleles for certain traits.5% of Down syndrome cases caused by a translocation in previous generation between chromosomes 21 and 14 o Not related to parental age but is inherited (C) McGraw Hill LLC 10 Chromosomal Mutations- Inversion A chromosome segment is turned 180?o Small portion of liver is removed and infected with retrovirus containing normal cholesterol receptor o Tissue is returned to patient (C) McGraw Hill LLC 24 Figure 13.13 Ex Vivo Gene Therapy in Humans Access the text alternative for slide images.(C) McGraw Hill LLC 2 Gene Mutations Gene: A segment of DNA that encodes for a functional product, typically a protein, crucial for cellular functions.Figure 13.9 Use of a Genetic Marker to Test for a Genetic Mutation (C) McGraw Hill LLC 17 Testing the DNA- DNA Microarrays Mutant alleles placed onto a DNA microarray, small silicone chip which is compared to DNA of a person to indicate risk of developing disease, which can be discussed with genetic counselor.Include deletions, duplications, inversions, and translocations.All rights reserved.2.3.4.?

Because learning changes everything.®
Chapter 13
Mutations and Genetic
Testing
Essentials of Biology
SEVENTH EDITION
Sylvia S. Mader
Michael Windelspecht
© McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.
Learning Outcomes

1. 
   
   
   
   2. 
      
      
      
      3. 
         
         
         
         4. Understand the mechanisms and effects of gene mutations, and the
            differences between point mutations and frameshift mutations.
            Identify chromosomal mutations and recognize their consequences
            and examples in humans.
            Describe genetic testing applications using karyotypes, genetic
            markers, and DNA testing methods for genetic disorders.
            Explain gene therapy, differentiating between ex vivo and in vivo
            methods, and the techniques to deliver genes to cells.
            © McGraw Hill LLC
            2
            Gene Mutations
            Gene: A segment of DNA that encodes for a functional product, typically a
            protein, crucial for cellular functions.
            Alleles: Variants of a gene that exist at the same locus on a
            chromosome, which can result in different phenotypic traits.
            Mutations: Permanent changes to the DNA sequence that may alter
            gene expression or function, influencing traits, and possibly leading to
            diseases. Many go undetected (no observable effect).
            Causes of Gene Mutations
            ▪ Spontaneous Mutations: Occur without external cause, due to
            replication error (rare due to proofreading) or caused by transposons.
            ▪ Induced Mutations: Caused by environmental agents (such as
            radiation and chemicals) that can alter DNA by changing nucleotide
            bases.
            © McGraw Hill LLC
            3
            Causes of Gene Mutations- Transposons
            "Jumping Genes“
         
         
         
         
      
      
      
      
   
   
   
   

• Pieces of DNA that can move within and between
  chromosomes, affecting gene function and regulation.
  Contribute to genetic diversity and have played roles in the evolution of
  genomes.
  © McGraw Hill LLC
  4
  Types and Effects of Mutations
  Point mutations
  • Change in a single DNA nucleotide
  • Results can be minor or severe. Can lead to different protein coding,
  potentially causing diseases like sickle cell anemia.
  Frameshift mutations
  • Insertions or deletions that disrupt the reading frame, affecting protein
  synthesis. All downstream codons affected.
  • Typically results in a nonfunctional protein. Usually much more severe.
  • THE CAT ATE THE RAT—C removed
  • THE ATA TET HER AT
  © McGraw Hill LLC
  5
  Figure 13.2 Varying Effects of a Point Mutation
  Access the text alternative for slide images.
  © McGraw Hill LLC
  (b, c): Eye of Science/Science Source 6
  Chromosomal Mutations
  Changes that involve large segments of DNA or whole
  chromosomes, affecting multiple genes. More common than
  changes in the chromosome number.
  Due to breakage and failure to reunite properly.
  Include deletions, duplications, inversions, and
  translocations.
  © McGraw Hill LLC
  7
  Chromosomal Mutations- Deletion
  • When a single break causes a chromosome to lose an end or two
  breaks result in the loss of an internal segment of the chromosome.
  Can lead to genetic disorders if essential genes are lost.
  • Williams syndrome—chromosome 7 loses a tiny end piece
  • Cri du chat—chromosome 5 loses an end piece
  © McGraw Hill LLC
  8
  Chromosomal Mutations- Duplication
  Chromosome segments are repeated
  Individual has more than two alleles for certain traits. Potentially
  leading to developmental abnormalities.
  Inv dup 15 syndrome—inverted duplication of chromosome 15
  • Inversion—segment joins in direction opposite from normal
  © McGraw Hill LLC
  9
  Chromosomal Mutations- Translocation
  Rearrangement of parts between
  nonhomologous chromosomes.
  Involves either swapping segments
  (reciprocal) or moving a segment
  without exchange (nonreciprocal).
  Unbalanced Translocation: Results
  in a net gain or loss of genetic
  material, potentially leading to
  genetic disorders like partial trisomy
  or partial monosomy.
  5% of Down syndrome cases caused
  by a translocation in previous
  generation between chromosomes
  21 and 14
  • Not related to parental age but is
  inherited
  © McGraw Hill LLC
  10
  Chromosomal Mutations- Inversion
  A chromosome segment is turned 180° (reversed end to end). Reverse
  sequence of alleles can lead to altered gene function if it disrupts
  control of gene expression.
  During meiosis, crossing-over can lead to recombinant chromosomes.
  • Alignment only possible when the inverted chromosome forms a loop
  © McGraw Hill LLC
  12
  Genetic Testing
  Genetic counseling—potential parents are advised on their risk of
  inherited disorders
  Counselor helps couple understand the mode of inheritance,
  medical consequences of disorder, and decisions they might wish
  to make
  Karyotyping—visual display of chromosomes arranged by size,
  shape, and banding pattern. Can help detect genetic
  abnormalities.
  • Can be from white blood cells or fetal cells by amniocentesis or
  chorionic villus sampling.
  © McGraw Hill LLC
  13
  Figure 13.7 Testing for Chromosomal Mutations
  • Not until 14th -17th week of pregnancy
  • 0.6% risk of spontaneous abortion
  • As early as 5th week of pregnancy
  • Greater risk of abortion (0.7%) but earlier
  results
  Access the text alternative for slide images.
  © McGraw Hill LLC
  14
  Figure 13.8 Karyotype Analysis
  Access the text alternative for slide images.
  © McGraw Hill LLC
  Kateryna Kon/Shutterstock 15
  Testing for a Protein
  Some disorders are caused by a missing enzyme
  • Test for quantity of enzyme produced
  © McGraw Hill LLC
  16
  Testing the DNA- Genetic Markers
  Relies on an abnormality in the DNA sequence due to presence of
  abnormal allele. Fragments from restriction enzyme will differ from
  a normal person’s results.
  Figure 13.9 Use of a Genetic Marker to Test for a Genetic Mutation
  © McGraw Hill LLC
  17
  Testing the DNA- DNA Microarrays
  Mutant alleles placed onto a DNA microarray, small silicone chip which is
  compared to DNA of a person to indicate risk of developing disease,
  which can be discussed with genetic counselor.
  Figure 13.10 Use of a DNA Microarray to Test
  for Mutated Genes
  © McGraw Hill LLC
  18
  DNA Sequencing
  • Individual’s complete genome
  • Important in personalized medicine
  • Can not only show risk for disease but also holds key to
  new treatment options
  • Based on genetic information, it is possible to improve
  patient outcomes and increase treatment options with
  increased precision
  • Becoming more affordable leading to popularity of
  personalized medicine
  © McGraw Hill LLC
  19
  Testing the Fetus
  Ultrasound—helps evaluate fetal anatomy for serious
  abnormalities
  • Uses high-frequency sound waves
  Testing fetal cells
  • Cells from amniocentesis or chorionic villus sampling
  • Fetal cells can also be collected from mother’s blood
  • PCR used to amplify DNA, no risk to fetus
  © McGraw Hill LLC
  20
  Testing the Embryo
  • Testing the embryo—
  following IVF, one cell
  can be removed from
  embryo without harm
  Access the text alternative for slide images.
  © McGraw Hill LLC
  (photo): Elyse Lewin/Exactostock-1555/SuperStock 21
  Testing the Egg
  • Testing egg—meiosis
  results in single egg and
  two polar bodies.
  • Polar bodies can be used
  in genetic testing.
  • If a woman is a
  heterozygote, when the
  polar body has the
  defective allele, the egg
  must be normal.
  © McGraw Hill LLC
  22
  Gene Therapy
  Insertion of genetic material into human cells for treatment of
  a disorder
  Two methods
  • Ex vivo (outside the body)—Cells are genetically modified
  outside the body and then reinserted into the patient.
  • In vivo (inside the body) — Direct delivery of genes into
  the body using vectors such as viruses.
  © McGraw Hill LLC
  23
  Ex Vivo Gene Therapy
  Treatment of SCID
  • Severe combined immunodeficiency
  • Lack enzyme involved in the maturation of cells producing
  antibodies
  • Bone marrow stem cells are removed and infected with RNA
  retrovirus carrying the gene for normal enzyme.
  • Cells are then returned to patient
  Treatment of familial hypercholesterolemia
  • High levels of cholesterol lead to early fatal heart attacks.
  • Small portion of liver is removed and infected with retrovirus
  containing normal cholesterol receptor
  • Tissue is returned to patient
  © McGraw Hill LLC
  24
  Figure 13.13 Ex Vivo Gene Therapy in Humans
  Access the text alternative for slide images.
  © McGraw Hill LLC
  25
  In Vivo Gene Therapy
  Cystic fibrosis treatment
  • Gene needed is sprayed into the nose or delivered to lower respiratory
  tract
  • Use adenoviruses or liposomes to carry gene
  Poor coronary circulation treatment
  • Vascular endothelial growth factor can cause growth of new blood
  vessels.
  • Genes coding for growth factor can be injected alone, or within a virus,
  into the heart to stimulate branching of coronary arteries.
  Rheumatoid arthritis
  • Immune system destroys person’s own body
  • Inject adenoviruses that contain anti-inflammatory genes into the
  affected joint
  © McGraw Hill LLC
  2