a. At least 6,000 human genes have been identified; many have been mapped to specific loci.

b. To analyze a genetically determined characteristic, one first needs to understand the mode of inheritance: whether it is autosomal, sex-linked, dominant, or recessive.

c. A pedigree shows this information, along with generations of individuals in families.

d. In pedigrees, squares represent males, circles represent females, and horizontal lines indicate marriage, or mating; the offspring, which comprise the sibship, are shown in birth order from left to right.

e. Fraternal and identical twins are distinguished in a pedigree by the lines leading to the sibship line, as shown in the text examples.

f. Pedigree generations are denoted with Roman numerals, and individuals within a generation are numbered with Arabic numbers.

g. Shading and dots indicate persons who exhibit a trait, or carry an allele for it, respectively.

h. Figure 19.1 shows three typical pedigrees.

i. In analyzing human pedigrees, X-linked traits tend to be easily identified, since all males carrying the allele for a trait would display the trait, and males with the trait would tend to pass it to their grandsons through their daughter carriers.

j. Section 16.12 covers X-linked inheritance in more detail.

k. For rare conditions, it is assumed that persons marrying into a family with the condition would not, on average, have the condition.

l. Recessive autosomal alleles, as opposed to dominant ones, are more difficult to analyze, as they may be hidden for generations in heterozygous individuals.

m. Traits that do not appear as regularly as expected are said to have reduced penetrance, as other factors prevent them from being expressed.

n. Sidebar 16.1 discusses the biochemistry of the ABO blood group.

a. A few human traits (e.g. the tasting of PTC) are the result of a single gene's expression.

b. Most human traits (e.g. human height) are the result of the action of several genes.

c. Human height (Figure 19.2) is an example of a quantitative characteristic, which can be better understood through graphing the effects of the various genes that contribute to the characteristic (Figure 19.3).

d. A polygenic trait, such as human height, results from the action of many genes.

a. Human chromosomes acquire distinctive banding patterns when dyed with quinacrine mustard (Q banding) or stained with Giemsa stain (G banding) (Figure 19.9).

b. Each human chromosome has a unique banding pattern, and the bands help locate genes and abnormalities.

c. Human chromosomes are further characterized by a convention that terms the short arm the p arm, and the long arm the q arm.

a. Nondisjunction, or failure of normal disjunction (separation), of chromosomes during meiosis can cause serious genetic problems (Figure 19.10).

b. Zygotes produced after nondisjunction are aneuploid, having either extra or missing chromosomes.

c. Monosomic individuals have just one copy of a particular chromosome; trisomic individuals have three copies; each of these cases is caused by nondisjunction.

d. Down syndrome (Figure 19.11) is caused by trisomy of chromosome number 21.

e. Trisomies become increasingly more likely as the mother ages, probably due to the extended time period of gametogenesis (recall, all of a woman's eggs are arrested during meiosis and any egg to be released during ovulation divides and matures just before being released).

f. A chromosome translocation occurs when a piece of one chromosome becomes attached to another; Figure 19.12 shows a 14/21 translocation.

a. Several syndromes in humans result from unusual numbers of sex chromosomes.

b. Turner syndrome (Figure 19.13) is caused in females by a 45 XO karyotype (45 chromosomes, with one X chromosome missing).

c. Klinefelter syndrome (Figure 19.14) is caused in males by nondisjunction that results in a 47 XXY, 48 XXXY, or 49 XXXXY karyotype.

d. Mary Lyon and Liane Russell proposed, in 1961, that each cell uses just one of its X chromosomes, and that the other X chromosome is inactivated (Figure 19.16).

e. Calico cats (Figure 19.15) display this phenomenon, as their fur is a mosaic of two cell types; differences between X chromosome activation in a female's cells cause phenotypic differences.

f. Lyon and Russell proposed that an inactivated X chromosome becomes condensed into a tight bundle named a Barr body (Figure 19.17); these chromosomes cannot be expressed (Section 18.10).

a. When hybrid cells are made by fusing human cells in tissue culture with cells from another animal (Figure 19.18), the chromosomes of one species or another tend to be lost as the cells grow.

b. Hybridization techniques have proved useful in assigning human genes to particular chromosomes, as human chromosomes, or parts thereof, are lost at random in hybrid cultures, and the cells can thus be analyzed for production, or nonproduction, of particular proteins.

c. Figure 19.19 illustrates how this technique was used for localizing the TK (thymidine kinase) gene to chromosome 17.

a. The allelic frequency is the percentage of time a given allele occurs in a population.

b. A mutant allele that becomes randomly distributed in a population, in frequencies equal to those for another allele to which it is linked, is said to be in linkage equilibrium.

c. A mutant allele that does not have time to achieve random distribution in a population would be in linkage disequilibrium with the randomly distributed allele to which it is linked (Figure 19.20).

d. In humans, if one allele's frequency is known, and can be compared to those of a disease-causing allele that is in linkage disequilibrium, the linkage of the two alleles, and thus the location of the mutant allele, might be demonstrated.

e. Gene mapping thus depends on some part of a chromosome that can serve as a marker.

f. Because known alleles are not always available, DNA fragments known as restriction fragment length polymorphisms (RFLPs), have been used as markers.

g. RFLPs are produced because restriction endonucleases cut the chromosomes of two genetically different persons in different locations; the DNA segments produced can be separated on a gel and probed (Section 18.1), as in Figure 19.21.

h. Sidebar 19.2 discusses the use of RFLPs in forensic medicine.

a. Recombinant DNA methods have been responsible for the identification and mapping of several genes related to human disease.

b. Restriction maps (Figure 19.22) show chromosome sites known to be cut by certain restriction enzymes.

c. Cystic fibrosis (CF) was discovered using restriction mapping techniques, and was shown to be caused by the deletion of three nucleotides that, when present in the genome, would remove a phenylalanine from the normal gene product.

d. The techniques for determining the locations and sequences of unknown genes are thus now available and are shown to have great potential for relieving human suffering.

a. Gene therapy, better known as gene transfer, involves substituting a normal gene for a defective one in the cells of a diseased person.

b. The CFTR gene was transformed into isolated cells using vaccinia virus (Figure 19.24 and Chapter 17), and when the virus was introduced into cells from a CF patient, the cells acquired normal ionic regulation.

c. As of 1996, several gene therapy centers are doing gene studies with CF adults, and various vectors are being examined, with limited success:

a. Increasing the level of knowledge regarding human genetics and associated diseases has also increased the number of questions concerning management of this information.