Hartl, Jones - Genetics. Principlers and analysis - 1998 (522927), страница 23
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(The term sibship refers to a group of offspring from the same parents.) The data indicatethat a human family is no more likely to have a girl on the next birth if it already has five boys than if it already hasfive girls. The statistical reason is that, though the sex ratios tend to balance out when they are averaged across alarge number of sibships, they do not need to balance within individual sibships.
Thus, among families in whichthere are five children, the sibships consisting of five boys balance those consisting of five girls, for an overall sexratio of 1 : 1. However, both of these sibships are unusual in their sex distribution.Page 50When events are independent (such as independent traits or successive offspring from a cross), the probabilities arecombined by means of the multiplication rule.Multiplication Rule: The probability of two independent events, A and B, being realized simultaneously isgiven by the product of their separate probabilities.In symbols, the multiplication rule isThe multiplication rule can be used to answer questions like the following one: Of two offspring from the matingAa × Aa, what is the probability that both have the dominant phenotype? Because the mating is Aa × Aa, theprobability that any particular offspring has the dominant phenotype equals 3/4.
The multiplication rule says thatthe probability that both of two offspring have the dominant phenotype is 3/4 × 3/4 = 9/16.Here is a typical genetic question that can be answered by using the addition and multiplication rules together: Oftwo offspring from the mating Aa × Aa, what is the probability of one dominant phenotype and one recessive?Sibships of one dominant phenotype and one recessive can come about in two different ways—with the dominantborn first or with the dominant born second— and these outcomes are mutually exclusive.
The probability of thefirst case is 3/4 × 1/4 and that of the second is 1/4 × 3/4 because the events are mutually exclusive, the probabilitiesare added. The answer is thereforeThe addition and multiplication rules are very powerful tools for calculating the probabilities of genetic events.Figure 2.14 shows how the rules are applied to determine the expected proportions of the nine different genotypespossible among the F2 progeny produced by self-pollination of a Ww Gg dihybrid.In genetics, independence applies not only to the successive offspring formed by a mating, but also to genes thatsegregate according to the principle of independent assortment (Figure 2.15). The independence means that themultiplication rule can be used to determine the probability ofFigure 2.14Example of the use of the addition and multiplication rules to determine theprobabilities of the nine genotypes and four phenotypes in the F2 progenyobtained from self-pollination of a dihybrid F1.
The Roman numerals arearbitrary labels identifying the F2 genotypes.Page 51Figure 2.15In genetics, two important types of independence are(A) independent segregation of alleles that showindependent assortment and (B) independentfertilizations resulting in successive offspring. Inthese cases, the probabilities of the individualoutcomes of segregation or fertilization aremultiplied to obtain the overall probability.the various types of progeny from a cross in which there is independent assortment among numerous pairs ofalleles. This principle is the theoretical basis for the expected progeny types from a trihybrid cross, shown in Figure2.12. One can also use the multiplication rule to calculate the probability of a specific genotype among the progenyof a cross. For example, if a quadruple heterozygote of genotype Aa Bb Cc Dd is self-fertilized, the probability of aquadruple heterozygote Aa Bb Cc Dd offspring is (1/2) (1/2) (1/2) (1/2) = (1/2)4, or 1/16, assuming independentassortment of all four pairs of alleles.2.4—Segregation in Human PedigreesDetermining the genetic basis of a trait from the kinds of crosses that we have considered requires that we controlmatings between organisms and obtain large numbers of offspring to classify with regard to phenotype.
Theanalysis of segregation by this method is not possible in human beings, and it is not usually feasible for traits inlarge domestic animals. However, the mode of inheritance of a trait can sometimes be determined by examining theappearance of the phenotypes that reflect the segregation of alleles in several generations of related individuals.This is typically done with a family tree that shows the phenotype of each individual; such a diagram is called apedigree. An important application of probability in genetics is its use in pedigree analysis.Figure 2.16 depicts most of the standard symbols used in drawing human pedigree. Females are represented bycircles and males by squares.
(A diamond is used if the sex of an individual is unknown.) Persons with thephenotype of interest are indicated by colored or shaded symbols. For recessive alleles, heterozygous carriers aredepicted with half-filled symbols. A mating between a female and a male is indicated by joining their symbols witha horizontal line, which is connected vertically to a second horizontal line below that connects the symbols for theiroffspring. The offspring within a sibship, called siblings or sibs regardless of sex, are represented from left to rightin order of their birth.Page 52Figure 2.16Conventional symbols used in depicting human pedigrees.A pedigree for the trait Huntington disease, which is due to a dominant allele, is shown in Figure 2.17.
Thenumbers in the pedigree are for convenience in referring to particular persons. The successive generations aredesignated by Roman numerals. Within any generation, all of the persons are numbered consecutively from left toright. The pedigree starts with the woman I-1 and the man I-2. He has Huntington disease, which is a progressivenerve degeneration that usually begins about middle age. It results in severe physical and mental disability and thendeath. The pedigree shows that the trait affects both sexes, that it is transmitted from affected parent to affectedoffspring, and that about half of all the offspring of anFigure 2.17Pedigree of a human family showing the inheritance of the dominant genefor Huntington disease.
Females and males are represented by circles andsquares, respectively. Red symbols indicate persons affected with the disease.Page 53Connection In Memoriam: This Land Is Your Land, This Land Is My LandThe Huntington's Disease Collaborative Research Group 1993Comprising 58 authors among 9 institutionsA Novel Gene Containing a Trinucleotide Repeat That is Expanded and Unstable on Huntington's DiseaseChromosomesModern genetic research is sometimes carried out by large collaborative groups in a number of researchinstitutions scattered across several countries.
This approach is exemplified by the search for the generesponsible for Huntington disease. The search was highly publicized because of the severity of the disease, thelate age of onset, and the dominant inheritance. Famed folk singer Woody Guthrie, who wrote "This Land Is YourLand" and other well-known tunes, died of the disease in 1967.
When the gene was identified, it turned out toencode a protein (now called huntingtin) of unknown function that is expressed in many cell types throughout thebody and not, as expected, exclusively in nervous tissue. Within the coding sequence of this gene is a trinucleotiderepeat (5'-CAG-3') that is repeated in tandem a number of times according to the general formula (5'-CAG-3')n.Among normal alleles, the number n of repeats ranges from 11 to 34 with an average of 18; among mutantalleles, the number of repeats ranges from 40 to 86. This tandem repeat is genetically unstable in that it can, bysome unknown mechanism, increase in copy number ("expand"). In two cases in which a new mutant allele wasanalyzed, one had increased in repeat number from 36 to 44 and the other from 33 to 49. This is a mutationalmechanism that is quite common in some human genetic diseases.
The excerpt cites several other examples. Theauthors also emphasize that their discovery raises important ethical issues, including genetic testing,confidentiality, and informed consent.Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor disturbance,cognitive loss, andWe consider it of the utmost importance that the current internationally accepted guidelines andcounseling protocols for testing people at risk continue to be observed, and that samples fromunaffected relatives should not be tested inadvertently or without full consent.psychiatric manifestations. It is inherited in an autosomal dominant fashion and affects approximately 1 in 10,000individuals in most populations of European origin.
The hallmark of HD is a distinctive choreic [jerky] movementdisorder that typically has a subtle, insidious onset in the fourth to fifth decade of life and gradually worsens overa course of 10 to 20 years until death. . . .The genetic defect causing HD was assigned to chromosome 4 in one ofthe first successful linkage analyses using DNA markers in humans. Since that time, we have pursued anapproach to isolating and characterizing the HD gene based on progressively refining its localization.
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