Changes in Chromosome Number Chapter 3

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

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)

XYY Karyotype

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

p arm Centromere q arm Figure 3.1: Anatomy of a Chromosome. The parts of a chromosome include the centromere and two arms (the short arm is the p arm, the long arm is the q arm). Fig. 3-1, p. 43

Animation: How Cells Reproduce (chromosome structure and organization)

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)

Meiosis: Produces Haploid Cells

Before cells begin meiosis, the chromosomes duplicate 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

to the centromere of each pair. This stage is called metaphase 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. p. 44

Members of each homologous pair separate and move toward opposite sides of the cell. This stage is called anaphase I. p. 44

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

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

Meiosis: Produces Haploid Cells

Two cells formed during meiosis I 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

The 23 chromosomes in each cell attach to spindle fibers at their centromeres. This stage is called metaphase II. p. 44

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

Finally, the chromosomes uncoil and the nuclear membrane re-forms 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

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

Events in Meiosis

Animation: Meiosis

Animation: Mitosis

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

Nondisjunction

Alignments at metaphase II 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 Figure 3.2: Nondisjunction. Nondisjunction can cause abnormal chromosome numbers in gametes (eggs or sperm). Nondisjunction at anaphase I Alignments at metaphase II Anaphase II Fig. 3-2, p. 45

Alignments at metaphase II Chromosome number in gametes: Extra chromosome (n + 1) Missing chromosome (n – 1) Anaphase II Alignments at metaphase II Nondisjunction at anaphase I Chromosomes align at metaphase I Figure 3.2: Nondisjunction. Nondisjunction can cause abnormal chromosome numbers in gametes (eggs or sperm). Stepped Art Fig. 3-2, p. 45

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

3.3 ID of Chromosomal Abnormalities Two tests: Amniocentesis (> 16 weeks) Collects amniotic fluid Fetal cells grown and karyotype produced Chorionic villus sampling (CVS) (10–12 weeks) Rapidly dividing cells Karyotype within few days

Amniocentesis

Fetal cells are removed from the solution Removal of about 20 ml of amniotic fluid containing suspended cells that were sloughed off from the fetus Biochemical analysis of the amniotic fluid 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

Fetal cells are removed from the solution Removal of about 20 ml of amniotic fluid containing suspended cells that were sloughed off from the fetus Biochemical analysis of the amniotic fluid 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 Stepped Art p. 46

Karyotype

Animation: Chromosomes and Human Inheritance (karyotype preparation)

Chorionic Villus Sampling (CVS)

Ultrasound to monitor procedure Chorionic villi Ultrasound to monitor procedure Developing placenta Developing fetus Bladder Uterus Chorion Catheter Amniotic cavity Rectum p. 47

Amniocentesis Only Used in Certain Conditions Risks for miscarriage; typically only done under one of following circumstances: Mother > 35 History of child with chromosomal abnormalities Parent has abnormal chromosomes Mother carries a X-linked disorder History of infertility or multiple miscarriages

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

Structural Changes in Chromosomes

p. 47

One segment repeated three times Normal chromosome One segment repeated three times p. 47

p. 47

Segment C deleted p. 47

p. 47

Segments G, H, I become inverted p. 47

p. 47

Chromosome A Chromosome B Translocation p. 47

Animation: Chromosome abnormalities exercise

Animation: Meiosis and Sexual Reproduction (Meiosis I and II)

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

Autosomal Trisomies

Autosomal Trisomies

Autosomal Trisomies

Trisomy 13: Patau Syndrome (47,+13) 1/15,000 Survival: 1–2 months Facial, eye, finger, toe, brain, heart, and nervous system malformations

Patau Syndrome

Trisomy 13: Edwards Syndrome (47,+18) 1/11,000, 80% females Survival: 2–4 months Small, mental disabilities, clenched fists, heart, finger, and foot malformations Die from heart failure or pneumonia

Edwards Syndrome

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

Down Syndrome

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

Maternal Age and Down Syndrome

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)

Sex Chromosome Trisomies

Sex Chromosome Trisomies

Sex Chromosome Trisomies

Turner Syndrome (45,X) Survival to adulthood Female, short, wide-chested, undeveloped ovaries, possible narrowing of aorta Normal intelligence 1/10,000 female births, 95–99% of 45,X conceptions die before birth

Turner Syndrome

Klinefelter Syndrome (47,XXY) Survival to adulthood Male Features do not develop until puberty, usually sterile, may have learning disabilities 1/1,000 males

Klinefelter Syndrome

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

XYY Syndrome

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

Counseling Recommendations (1) Pregnant women or those who are planning pregnancy Women > age 35 Couples with a child with: Mental retardation A genetic disorder A birth defect

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

Genetic Counseling Most see a genetic counselor: 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

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

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

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

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?

Wrongful-Birth and Wrongful-Life Cases

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

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?

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?