Chromosomes consist of DNA, proteins, and structures like telomeres and centromeres. Chromosomal abnormalities can include aneuploidy (extra or missing chromosomes) and polyploidy (extra sets of chromosomes). These abnormalities can be detected through techniques like amniocentesis, chorionic villus sampling, and analyzing fetal cells in maternal blood, which allow chromosomal analysis to screen for conditions like Down syndrome, Turner syndrome, and Klinefelter syndrome. Nondisjunction during cell division can result in aneuploidies, while errors in meiosis can also produce chromosomal abnormalities.

2. Portrait of a Chromosome
 Mutations range from single-base changes to entire
extra sets of chromosomes
 A mutation is considered a chromosomal aberration if
 it is large enough to see with a light microscope using
stains and/or fluorescent probes to highlight missing,
extra, or moved genetic material.
 Cytogenetics is the subdiscipline within genetics that
links chromosome variations to specific traits,
including illnesses

3. Required Parts: Telomeres and Centromeres
 A chromosome consists primarily of DNA and proteins
with a small amount of RNA
 Heterochromatin consists mostly of highly repetitive
DNA sequences, whereas euchromatin has more
protein-encoding sequences
 A chromosome must include structures that enable it
to replicate and remain intact
 Everything else is essentially informational cargo
(protein-encoding genes and their controls).

4.  The essential parts of a chromosome are:
 telomeres
 origin of replication sites, where replication forks begin to
form
 the centromere
 The centromere is the largest constriction of a
chromosome and it is where spindle fibers attach
when the cell divides
 Centromeres are replicated toward the end of S phase.
 A protein that may control their duplication is called
centromere protein A, or CENP-A

6. Karyotypes Chart Chromosomes
 A karyotype displays chromosomes in pairs by size and
by physical landmarks that appear during mitotic
metaphase, when DNA coils tightly
 The 24 human chromosome types are numbered from
largest to smallest—1 to 22. The other two
chromosomes are the X and the Y

7.  A chromosome is metacentric if the centromere
divides it into two arms of approximately equal length.
 It is submetacentric if the centromere establishes one
long arm and one short arm
 And acrocentric if it pinches off only a small amount
of material toward one end
 Telocentric chromosomes that have only one arm, but
humans do not.
 The long arm of a chromosome is designated q, and
the short arm p ( p stands for “petite”).

9. Visualizing Chromosomes
 Extra or missing chromosomes are detected by counting a
number other than 46.
 Identifying chromosome rearrangements, such as an
inverted sequence or an exchange of parts between two
chromosomes, requires a way to distinguish among the
chromosomes.
 A combination of stains and DNA probes applied to
chromosomes allows this.
 A DNA probe is a labeled piece of DNA that binds to its
complementary base sequence on a particular chromosome

10. Obtaining Cells for Chromosome Study
 Any cell other than a mature red blood cell (which lacks a
nucleus) can be used to examine chromosomes
 Amniocentesis and chorionic villus sampling have been
available for many years.
 They sample fetal cells from the amniotic fluid and chorionic
villi, respectively, and detect large-scale chromosomal
abnormalities.
 A newer technique called chromosome microarray analysis
can be paired with the older techniques to detect copy number
variants, which include extremely small sections of missing or
extra DNA.
 Chromosome microarray analysis probes and displays specific
sequences, detecting many disorders that other techniques miss

11. Amniocentesis
 A small sample of fetal cells and fluids is removed from the
uterus with a needle passed through the woman’s
abdominal wall
 The cellsare cultured for a week to 10 days, and typically 20
cells are karyotyped.
 The sampled amniotic fluid may also be examined for
deficient, excess, or abnormal biochemicals that could
indicate an inborn error of metabolism.
 Amniocentesis can detect approximately 1,000 of the more
than 5,000 known chromosomal and biochemical
problems

12.  The most common chromosomal abnormality
detected is one extra chromosome, called a trisomy.
 Amniocentesis is usually performed between 14 and 16
weeks gestation, when the fetus isn’t yet very large but
amniotic fluid is plentiful
 The procedure is also warranted if a couple has had
several spontaneous abortions or children with birth
defects or a known chromosome abnormality,
irrespective of maternal age

14. Chorionic Villus Sampling
 During the 10th through 12th week of pregnancy, chorionic
villus sampling (CVS) obtains cells from the chorionic villi
 Which are finger-like structures that develop into the
placenta
 A karyotype is prepared directly from the collected cells,
rather than first culturing them, as in amniocentesis
 Because chorionic villus cells descend from the fertilized
ovum, their chromosomes should be identical to those of
the embryo and fetus.

15.  Occasionally, a chromosomal aberration occurs only in a
cell of the embryo, or only in a chorionic villus cell
 This results in chromosomal mosaicism—the karyotype of
a villus cell differs from that of an embryo cell
 CVS is slightly less accurate than amniocentesis, and in
about 1 in 1,000 to 3,000 procedures
 It halts development of the feet and/or hands
 A condition termed transverse limb defects.
 Also, CVS does not sample amniotic fluid, so tests for
inborn errors of metabolism are not possible

16. Fetal Cells, DNA, and RNA
 Detecting fetal cells or nucleic acids in the pregnant woman’s
bloodstream is safer than amniocentesis and CVS
 The technique traces its roots to 1957, when a pregnant woman
died when cells from a very early embryo lodged in a major blood
vessel in her lung, blocking blood flow
 Researchers found that fetal cells enter the maternal circulation
in up to 70 percent of pregnancies.
 Cells from female embryos, however, cannot easily be
distinguished from the cells of the pregnant woman on the basis
of sex chromosome analysis.
 But fetal cells from either sex can be distinguished from
maternal cells using a device called a fluorescence-activated cell
sorter.

17.  It separates fetal cells from maternal blood by
identifying surface characteristics that differ from
those on the woman’s cells.
 The fetal cells are then karyotyped and specific gene
tests performed on fetal DNA
 Free fetal DNA is also in a pregnant woman’s
bloodstream but is difficult to detect because it is so
rare.
 A new technique detects fetal mRNA in the woman’s
bloodstream

18.  Down syndrome (an extra chromosome 21),
 Turner syndrome (also called XO syndrome, a female
with only one X chromosome)
 And Klinefelter syndrome (also called XXY syndrome,
a male with an extra X chromosome)
 Trisomy 18 is also called Edward syndrome
 and trisomy 13 is also known as Patau syndrome

22. Abnormal Chromosome Number
 A human karyotype is abnormal if the number of
chromosomes in a somatic cell is not 46
 Or if individual chromosomes have extra, missing, or
rearranged genetic material
 Abnormal chromosomes account for at least 50
percent of spontaneous abortions

23. Polyploidy
 The most drastic upset in chromosome number is an entire extra
set. A cell with extra sets of chromosomes is polyploid.
 An individual whose cells have three copies of each chromosome
is a triploid (designated 3N, for three sets of chromosomes).
 Two-thirds of all triploids result from fertilization of an oocyte
by two sperm
 The other cases arise from formation of a diploid gamete, such as
when a normal haploid sperm fertilizes a diploid oocyte
 However, certain human cells may be polyploid. The liver, for
example, has some tetraploid (4N) and even octaploid (8N) cells

25. Aneuploidy
 Cells missing a single chromosome or having an extra one are
aneuploid, which means “not good set.”
 A normal chromosome number is euploid, which means “good
set.”
 The meiotic error that causes aneuploidy is called
nondisjunction.
 Recall that in normal meiosis, homologs separate and each of
the resulting gametes receives only one member of each
chromosome pair.
 In nondisjunction, a chromosome pair fails to separate at
anaphase of either the first or second meiotic division.
 This produces a sperm or oocyte that has two copies of a
particular chromosome, or none, rather than the normal one
copy

26.  Different trisomies tend to be caused by nondisjunction in the
male or female, at meiosis I or II
 Aneuploidy and polyploidy also arise during mitosis, producing
groups of somatic cells with the extra or missing chromosome
 An individual with two chromosomally distinct cell populations
is a mosaic
 Another meiotic error that leads to unbalanced genetic material
is the formation of an isochromosome, which is a chromosome
that has identical arms
 Inheriting two chromosomes or chromosome segments from one
parent is called uniparental disomy (UPD) (“two bodies from
one parent”).