Changes in Chromosome Number

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Changes in Chromosome Number

• Chapter 3

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Central Points

• Chromosomes are composed of DNA and proteins
• Most humans have 46 chromosomes
• Possible to test fetal chromosome number
• Extra chromosomes affect fetus
• Problems with genetic testing can result in
  lawsuits

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Case A Results Worry Pregnant Woman

• Martha, age 41, is 18-weeks pregnant
• Increased risk of chromosomal abnormalities
• Amniocentesis recommended
• Test results
• No Down syndrome
• Fetus is XYY (Jacobs syndrome)

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XYY Karyotype
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3.1 Chromosomes

• Thread-like structures in nucleus
• Carry genetic information
• Humans have 46
• Parts
• Centromere
• p arm
• q arm
• Telomeres

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p arm
Centromere
q arm
Fig. 3-1, p. 43
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Animation How Cells Reproduce (chromosome
structure and organization)
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3.2 Changes in Chromosome Number

• Eggs and sperm are produced by meiosis
• Begin with two copies of each chromosome (46)
• Two divisions meiosis I and meiosis II
• Homologous chromosome pairs separate
• Produces haploid cells with one copy of each
  chromosome (23)

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Meiosis Produces Haploid Cells
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Before cells begin meiosis, the chromosomes
duplicate. As meiosis begins, chromosomes coil
and shorten, and become visible in the
microscope. Each chromosome has a matching
partner and the two chromosomes may exchange
parts (cross over) during this stage, called
prophase I.
p. 44
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The chromosome pairs line up along the middle of
the cell, and spindle fibers attach to the
centromere of each pair. This stage is called
metaphase I.
p. 44
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Members of each homologous pair separate and move
toward opposite sides of the cell. This stage is
called anaphase I.
p. 44
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The chromosomes reach opposite poles of the cell,
and the nuclei begin to re-form. This stage is
called telophase I. The cytoplasm divides, and
two cells are formed. These cells have half the
number of chromosomes of the original cells and
are called haploid cells.
p. 44
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MEIOSIS I
Before cells begin meiosis, the chromosomes
duplicate. As meiosis begins, chromosomes coil
and shorten, and become visible in the
microscope. Each chromosome has a matching
partner and the two chromosomes may exchange
parts (cross over) during this stage, called
prophase I.
The chromosome pairs line up along the middle of
the cell, and spindle fibers attach to the
centromere of each pair. This stage is called
metaphase I.
Members of each homologous pair separate and move
toward opposite sides of the cell. This stage is
called anaphase I.
The chromosomes reach opposite poles of the cell,
and the nuclei begin to re-form. This stage is
called telophase I. The cytoplasm divides, and
two cells are formed. These cells have half the
number of chromosomes of the original cells and
are called haploid cells.
Stepped Art
p. 44
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Meiosis Produces Haploid Cells
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Two cells formed during meiosis I. In prophase
II, the chromosomes of these cells become coiled,
and move toward the center of the cell.
p. 44
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The 23 chromosomes in each cell attach to spindle
fibers at their centromeres. This stage is called
metaphase II.
p. 44
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Each centromere divides, and the newly formed
chromosomes (also called sister chromatids) move
to opposite ends of the cell. This stage is
called anaphase II.
p. 44
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Finally, the chromosomes uncoil and the nuclear
membrane re-forms. This stage is called telophase
II. After the cytoplasm divides, the result is
four cells, each with the haploid number of
chromosomes. Meiosis is now completed.
p. 44
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MEIOSIS II
Two cells formed during meiosis I. In prophase
II, the chromosomes of these cells become coiled,
and move toward the center of the cell.
The 23 chromosomes in each cell attach to spindle
fibers at their centromeres. This stage is called
metaphase II.
Each centromere divides, and the newly formed
chromosomes (also called sister chromatids) move
to opposite ends of the cell. This stage is
called anaphase II.
Finally, the chromosomes uncoil and the nuclear
membrane re-forms. This stage is called telophase
II. After the cytoplasm divides, the result is
four cells, each with the haploid number of
chromosomes. Meiosis is now completed.
Stepped Art
p. 44
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Events in Meiosis
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Animation Meiosis
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Animation Mitosis
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Nondisjunction

• Chromosomes fail to separate
• Results in gametes and zygote with an abnormal
  chromosome number
• Aneuploidy is variations in chromosome number
  that involve one or more chromosomes
• Most aneuploidy from errors in meiosis

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Nondisjunction
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Chromosome number in gametes
Extra chromosome (n 1)
Extra chromosome (n 1)
Missing chromosome (n 1)
Missing chromosome (n 1)
Chromosomes align at metaphase I
Nondisjunction at anaphase I
Alignments at metaphase II
Anaphase II
Fig. 3-2, p. 45
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Stepped Art
Fig. 3-2, p. 45
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Aneuploidy

• Effects vary by chromosomal condition
• Many cause early miscarriages
• Leading cause of mental retardation

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3.3 ID of Chromosomal Abnormalities

• Two tests
• Amniocentesis (gt 16 weeks)
• Collects amniotic fluid
• Fetal cells grown and karyotype produced
• Chorionic villus sampling (CVS) (1012 weeks)
• Rapidly dividing cells
• Karyotype within few days

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Amniocentesis
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Removal of about 20 ml of amniotic ?uid
containing suspended cells that were sloughed off
from the fetus
Biochemical analysis of the amniotic ?uid after
the fetal cells are separated out
Centrifugation
Fetal cells are removed from the solution
Analysis of fetal cells to determine sex
Cells are grown in an incubator
Karyotype analysis
p. 46
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Stepped Art
p. 46
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Karyotype
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Animation Chromosomes and Human Inheritance
(karyotype preparation)
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Chorionic Villus Sampling (CVS)
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Chorionic villi
Ultrasound to monitor procedure
Developing placenta
Developing fetus
Bladder
Uterus
Chorion
Catheter
Amniotic cavity
Rectum
p. 47
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Amniocentesis Only Used in Certain Conditions

• Risks for miscarriage typically only done under
  one of following circumstances
• Mother gt 35
• History of child with chromosomal abnormalities
• Parent has abnormal chromosomes
• Mother carries a X-linked disorder
• History of infertility or multiple miscarriages

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Other Chromosomal Variations

• Polyploidy multiple sets of chromosomes
• Euploid normal two copies of each chromosome
• Trisomy three copies of one chromosome
• Monosomy only one copy of a chromosome
• Structural changes duplication, deletion,
  inversion, translocation

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Structural Changes in Chromosomes
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p. 47
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Normal chromosome
One segment repeated three times
p. 47
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p. 47
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Segment C deleted
p. 47
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p. 47
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Segments G, H, I become inverted
p. 47
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p. 47
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Chromosome A
Chromosome B
Translocation
p. 47
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Animation Chromosome abnormalities exercise
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Animation Meiosis and Sexual Reproduction
(Meiosis I and II)
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3.4 Effects of Changes in Chromosomes

• Vary by chromosome and type of variation
• May cause birth defects or fetal death
• Monosomy of any autosome is fatal
• Only a few trisomies result in live births

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Autosomal Trisomies
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Autosomal Trisomies
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Autosomal Trisomies
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Trisomy 13 Patau Syndrome (47,13)

• 1/15,000
• Survival 12 months
• Facial, eye, finger, toe, brain, heart, and
  nervous system malformations

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Patau Syndrome
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Trisomy 13 Edwards Syndrome (47,18)

• 1/11,000, 80 females
• Survival 24 months
• Small, mental disabilities, clenched fists,
  heart, finger, and foot malformations
• Die from heart failure or pneumonia

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Edwards Syndrome
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Trisomy 21 Down Syndrome (47,21)

• 1/800 (changes with age of mother)
• Survival up to age 50
• Leading cause of childhood mental retardation and
  heart defects
• Wide, flat skulls eyelid folds large tongues
  physical, mental, development retardation
• May live rich, productive lives

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Down Syndrome
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Leading Risk Factor for Trisomy

• Maternal age
• Unknown why, older eggs increase risk of
  nondisjunction
• Eggs held in meiosis I from birth to ovulation
• Possible changes in maternal selection

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Maternal Age and Down Syndrome
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Aneuploidy and Sex Chromosomes

• More common than in autosomes
• Turner syndrome (45,X) monosomy of X chromosome
• Klinefelter syndrome (47,XXY)
• Jacobs syndrome (47,XYY)

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Sex Chromosome Trisomies
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Sex Chromosome Trisomies
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Sex Chromosome Trisomies
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Turner Syndrome (45,X)

• Survival to adulthood
• Female, short, wide-chested, undeveloped ovaries,
  possible narrowing of aorta
• Normal intelligence
• 1/10,000 female births, 9599 of 45,X
  conceptions die before birth

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Turner Syndrome
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Klinefelter Syndrome (47,XXY)

• Survival to adulthood
• Male
• Features do not develop until puberty, usually
  sterile, may have learning disabilities
• 1/1,000 males

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Klinefelter Syndrome
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XYY or Jacobs Syndrome (47,XYY)

• Survival to adulthood
• Average height, thin, personality disorders, some
  form of mental disabilities, and adolescent acne
• Some may have very mild symptoms
• 1/1,000 male births

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XYY Syndrome
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3.5 Ways to Evaluate Risks

• Genetic counselors are part of the health care
  team
• In nondirective way, they assist understanding
  of
• Risks
• Diagnosis
• Progression
• Possible treatments
• Management of disorder
• Possible recurrence

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Counseling Recommendations (1)

• Pregnant women or those who are planning
  pregnancy
• Women gt age 35
• Couples with a child with
• Mental retardation
• A genetic disorder
• A birth defect

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Counseling Recommendations (2)

• Couples from certain ethic groups
• Couples that are closely related
• Individuals with jobs, lifestyles, or medical
  history that may pose a risk to a pregnancy
• Women who have had two or more miscarriages or
  babies who died in infancy

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Genetic Counseling

• Most see a genetic counselor
• After a prenatal test
• After the birth of a child or
• To determine their risk
• Counselor
• Constructs a detailed family history and pedigree
• Shares information that allows an individual or a
  couple to make informed decisions

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Case A Questions

• Child is XYY What are the best options?
• Would the options change if the child had a
  different condition?
• Who should know?
• See the textbook for further questions on this
  case

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Case B Test Results Worry Doctor

• 31-year-old woman gave birth to a child with
  serious abnormalities
• Sued doctor for not performing amniocentesis
• What legal issues should concern the doctor and
  what should she do?
• See the textbook for further questions on this
  case

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Future of Genetic Counseling

• Human Genome Project (HGP) changed medical care
  and genetic testing
• Genetic counselor will become more important
• Evaluate reproductive risks and other conditions
• Allow at-risk individuals to make informed
  choices about lifestyle, children, and medical
  care

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3.6 Legal and Ethical Issues

• Wrongful-birth suit
• Wrongful-life suit
• Based on
• Could a diagnosis of this condition have been
  made in time to have an abortion?
• Was the condition serious enough that a
  reasonable person would have had an abortion?

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Wrongful-Birth and Wrongful-Life Cases
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Issues with Wrongful-Birth and Wrongful-Life
Suits

• Wrongful-birth suit (most states allow)
• Roe v. Wade gave a woman an alternative to birth
• Doctors have extensive medical malpractice
  insurance
• Wrongful-life suits (only 5 states allow)
• Courts uncomfortable declaring someone should
  never have been born

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XYY Individuals (Jacobs Syndrome)

• Early studies linking XYY with aggressive/
  criminal behavior no longer supported by research
• Should parents and or child know the condition?
• What should the doctor do?

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Spotlight on Law Becker v. Schwartz

• Becker, age 37, was not informed about
  amniocentesis
• Child born with Down syndrome, parents sued
  doctor for wrongful life
• Parents won 2,500 and gave baby up for adoption
• What is your opinion on this case?