Figure 1. Risk of chromosomal abnormalities by maternal age. Adapted from Ferguson-Smith and Yates (1984), Hook and Chamber (1977), Hook (1981 and 1990).

Figure 2. Normal meiosis (left) and nondisjunction (right). Only one of the 23 chromosome pairs is demonstrated; assume all other chromosome pairs undergo normal meiosis. Numbers reflect the total number of chromosomes in the gamete at that stage in meiosis.

Figure 3. (a) Normal karyotype. (b) Karyotype of an individual with Down syndrome, characterized by an extra chromosome 21, provided by either egg or sperm. This karyotype is written: 47,XY,+21, demonstrating that there are 47 total chromosomes, the sex chromosomes are X and Y (male), and the extra chromosome is a number 21. For a female with Down syndrome, the karyotype would be: 47,XX,+21. Courtesy of Dynagene Cytogenetics Laboratory, Swedish Medical Centre, Seattle, WA, USA.

Figure 4. Development of various cell lines in the human embryo. The fertilized egg (1) gives rise to a trophoblast precursor (1b) and a totipotent stem cell (2), which produces another trophoblast precursor (2b) and a stem cell (3), which give rise to the inner cell mass. This divides into stem cells and becomes the hypoblast (hy, 3b) and epiblast (ep, 4). Only a few of the epiblast cells go on to form the embryo in the inner cell mass. (5) CVS, chorionic villus sampling. ys, yolk sac; ps, primitive streak. Reproduced with permission of Wiley Liss Inc., New York, from Bianchi DW et al. (1993) Origin of extraembryonic mesoderm in experimental animals: relevance to chorionic mosaicism in humans. American Journal of Medical Genetics 46: 542–550.

Figure 5. (a) Transabdominal and (b) transcervical chorionic villus sampling. Courtesy of Dr Robert Saul, Greenwood Genetic Center, Greenwood, SC; from Counseling Aids for Geneticists, 3rd edn, 1995.

Figure 6. Prenatal diagnosis by amniocentesis. Courtesy of Dr Robert Saul of Greenwood Genetic Center, Greenwood, SC; from Counselling Aids for Geneticists, 3rd edn, 1995.

Figure 7. Percutaneous umbilical blood sampling. Courtesy of Dr Robert Saul of Greenwood Genetic Center, Greenwood, SC; from Counseling Aids for Geneticists, 3rd edn, 1995.

Figure 8. Ultrasound image demonstrating the measurement of nuchal translucency (the ‘nuchal fold’) at the back of the fetal neck. Increased nuchal thickness (>2 mm in the first trimester; >5 mm in the second trimester) has been associated with increased risk of Down syndrome (and other aneuploidies) and is therefore considered a marker for these conditions. Courtesy of Dr Vivienne Souter, Swedish Medical Center, Seattle, WA, USA.

Figure 9. An example of fluorescence in situ hybridization (FISH) analysis, wherein interphase nuclei from an amniocentesis sample are hybridized with probes for chromosomes 13, 18, 21, X and Y. (a) A nucleus has been hybridized with probes for chromosomes 18 (aqua), X (green) and one Y (red). (If this had been a female fetus, there would have been two green lights and no red.) (b) A nucleus has been hybridized with probes for chromosomes 13 (green) and 21 (red). There are two number 13 chromosomes (normal) and three copies of chromosome number 21 (indicating Down syndrome). Overall result: male fetus with Down syndrome. Courtesy of Dynagene Cytogenetics Laboratory, Swedish Medical Center, Seattle, WA, USA.

Figure 10. Direct mutation analysis with restriction enzymes. (a) Sickle cell anaemia and -haemoglobin gene. Sickle cell anaemia is caused by a base-pair substitution in which adenine is changed to a thymine. MstII is restriction enzyme that cuts the specific DNA sequence shown in the figure. MstII will splice exon I of the HbA; however, MstII will not splice HbS because it does not recognize the restriction site due to the AT mutation. (b) Southern blot analysis depicts the results of gel electrophoresis of an individual homozygous for the sickle cell mutation (lane 1; sickle cell anaemia), heterozygous for normal and sickle cell (lane 2; sickle cell trait/carrier status) and homozygous for the normal alleles (lane 3; unaffected, not a carrier).

Figure 11. Sequencing restriction enzymes and polymerase chain reaction (PCR) (Sanger dideoxy method).

Figure 12. Representative dot blot analysis of one of the most common cystic fibrosis mutations (F508). Individual membranes are hybridized with an end-labelled oligonucleotide probe that detects either the normal sequence (left) or the sequence with the F508 mutation (right). Individuals’ amplified DNA samples are each blotted twice, once on each membrane. (Each patient's DNA is blotted in the same column and row on each membrane.) Results from the first row of this blot are as follows: 1-1 and 1-5 are both normal, homozygous for the normal sequence. 1-2 is a heterozygous carrier, amplifying on both membranes. Both 1-3 and 1-4 show affected individuals, hybridizing only with the F508 probe. Courtesy of Kristen Skogerbe, Molecular Laboratory, Swedish Medical Center, Seattle, WA, USA.

Figure 13. Linkage analysis. Polymorphisms A and B closely flank the disease gene locus, establishing the linkage phases: AB = mutation present; ab = mutation absent.

Figure 14. Spectral karyotype demonstrating duplication of chromosome 9 affixed (arrow) to the bottom of chromosome 4. Further analysis with reverse chromosome banding (see images to the left of each chromosome) allowed for further analysis of the breakpoints. This individual is missing a small segment at the bottom of chromosome 4 (the ‘q arm’ of the chromosome), and has a duplication for the top of chromosome 9 (the ‘p arm’ of the chromosome). Results: 46,XY,der(4)t(4;9)(q35.1;p12). A subsequent review of the literature found that this patient's developmental delay and clinical features indeed matched those described for duplication 9p syndrome (Jones, 1997). Courtesy of Dr Kent Opheim, Children's Hospital and Medical Center of Seattle.