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

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

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

Meiosis: Produces Haploid Cells

Animation: Meiosis

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

Meiosis: The Creations of Gametes

Non-Disjunction During Meiosis Non-disjunction in Meiosis 1 Non-disjunction in Meiosis 2

Monosomy zygote Trisomy zygote

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

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

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

Chorionic Villus Sampling (CVS)

Karyotype

Animation: Chromosomes and Human Inheritance (karyotype preparation)

Non-Invasive Prenatal Diagnosis In 1997 it was determined the “cell-free” fetal DNA is found in maternal plasma Has been used to determine the sex and blood group of the fetus Harder to detect fetal chromosomal aneuploidies, because fetal DNA is only 3% of cell-free DNA in maternal plasma

Other Chromosomal Variations Haploid: one copy of each chromosome Diploid: normal two copies of each chromosome Polyploidy: multiple sets of chromosomes Aneuploid: A variation in chromosome number, but not involving all of the chromosomes Trisomy: three copies of one chromosome Monosomy: only one copy of a chromosome Structural changes: duplication, deletion, inversion, translocation

Duplication

Deletion

Karyotype of Deletion on Chromosome 16

Inversion

Translocation

Translocation Karyotype

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

Patau Syndrome

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

Edwards Syndrome

Trisomy 18: 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

Down 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; large tongues; physical, mental, development retardation

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)

Turner Syndrome

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

Klinefelter Syndrome

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

XYY 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

3.5 Ways to Evaluate Risks Genetic counselors are part of the health care team 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, after age 35 Couples with a child with: Mental retardation A genetic disorder A birth defect

Counseling Recommendations (2) Couples from certain ethnic 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

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