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

Meiosis 1

Meiosis 2

Non-Disjunction During Meiosis

Non-disjunction in Meiosis 1 Non-disjunction in Meiosis 2

Trisomy zygoteMonosomy 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

p. 46

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

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:• 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