Human Genetics: Concepts and Applications (Lewis), 9th Edition

Chapter 13: Chromosomes

Chapter Outline

CHAPTER OVERVIEW

1. Some mutations are observable at the chromosome level, and these large alterations are the focus of this chapter.
2. Excess or deficient genetic material can cause medical syndromes or damage prenatal development.
3. Cytogenetics is the study of chromosome abnormalities and associated effects on health or other traits.

1. Chromosomes consist of DNA and proteins. Staining reveals dark regions termed heterochromatin and lighter areas called euchromatin.
2. Telomeres consist of repeat sequences and protect chromosome tips.
3. A centromere is a constricted site where spindle fibers attach during cell division.
4. Centromeres are regions of repeated DNA bound to centromere-associated proteins.

1. Karyotypes are charts that display chromosomes in size order.
2. Chromosomes are numbered from largest to smallest, 1 through 22, plus X and Y.
3. Chromosomes are distinguished by size, centromere location, differential staining, and DNA probes.
4. The short arm of a chromosome is called the "p" arm and the long arm is
designated "q."

5. Five human chromosomes (13, 14, 15, 21, and 22) have satellites, which carry repeats of genes encoding ribosomal components.
6. Translocations result in exchanges of material between two chromosomes.
7. Some cancers arise from translocations.

1. Any cell with a nucleus can be used to obtain chromosomes to prepare a karyotype.
2. Fetal karyotypes are constructed from cells obtained by amniocentesis, chorionic villus sampling, and chromosome microarray analysis.
3. Fetal karyotypes are prepared for patients with advanced maternal age, repeated miscarriages, and increased risk of a chromosomal anomaly as indicated by a maternal serum marker test or family history.
4. Techniques are also available to separate fetal cells, DNA and RNA from maternal blood for screening and analysis.

1. To obtain chromosomes for karyotyping, cells are halted in metaphase, broken open on a glass slide, and the chromosomes spread over the surface.
2. Traditionally, chromosomes were stained, identified, and arranged in order of size and centromere location.
3. Newer, fluorescent in situ hybridization (FISH) techniques use chromosome specific probes and fluorescent dyes to "paint" chromosomes and create karyotypes.
4. Chromosomal shorthand describes the total number of chromosomes, types of sex chromosomes, and any aberrations present.
5. Ideograms are maps of the distinguishing features of individual chromosomes.

1. Polyploid cells have extra chromosome sets and are designated by the number of complete sets they contain — triploid, tetraploid, etc.
2. They may result from fertilization of an oocyte by two sperm or one sperm fertilizing a diploid oocyte.
3. Polyploidy is tolerated in plants, but is a common cause of spontaneous abortion in humans.

1. Aneuploidy refers to the loss or gain of individual chromosomes. A euploid cell has a normal chromosome number (46).
2. Individuals with trisomies are more likely to survive than those with monosomies.
3. Sex chromosome aneuploidy is less severe than autosomal aneuploidy.
4. This condition most often results from meiotic nondisjunction.
5. The most common autosomal aneuploids seen in newborns are trisomies 13, 18
and 21.

6. Sex chromosome aneuploids include XO (Turner syndrome), triplo-X females, XXY males (Klinefelter syndrome), and XYY males.

1. Deletions and duplications are considered copy number variants.
2. Many microduplications and microdeletions are too small to be detected by traditional karyotyping techniques but have important implications for health.
3. These are detected by comparative genome hybridization.

1. In a Robertsonian translocation, the two long arms of nonhomologous chromosomes fuse, creating one large translocation chromosome. The short arms are lost.
2. In a reciprocal translocation, two nonhomologous chromosomes exchange parts.
3. A translocation that deletes, duplicates, or disrupts a gene can harm health.
4. Translocation carriers may have a normal phenotype but may have affected children.

1. Inversions result when part of a chromosome flips, and may affect health.

1. An isochromosome has two identical arms and therefore introduces duplications and deletions.
2. Isochromosomes arise in meiosis when the centromere splits in the wrong plane.
3. Ring chromosomes arise when telomeres are lost, leaving sticky ends that close and form rings.
4. While ring chromosomes are usually comprised of DNA repeats and do not affect health, some can produce symptoms.

1. Uniparental disomy (UPD) results when two chromosomes or chromosome parts are inherited from the same parent, doubling part of one parent's contribution.
2. UPD can arise from a trisomy and subsequent chromosome loss, or from two nondisjunction events.
3. UPD can cause disease if it creates a homozygous recessive condition associated with an illness.
4. UPD can also cause disease by disrupting genomic imprinting.