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Tamarin: Principles of Genetics, Seventh Edition
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II. Mendelism and the Chromosomal Theory
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5. Sex Determination, Sex Linkage, and Pedigree Analysis
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The McGraw Hill Companies, 2001
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This chapter begins a four-chapter sequence that analyzes the relationship of genes to chromosomes. We begin with the study of sex determination.
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STUDY OBJECTIVE 1: To analyze the causes of sex deterlar mosaicism for most loci on the X chromosome. In Drosophila, the X chromosome in males is hyperactive. STUDY OBJECTIVE 3: To analyze the inheritance patterns of traits that loci on the sex chromosomes control 95 97 Since different chromosomes are normally associated with each sex, inheritance of loci located on these chromosomes shows speci c, nonreciprocal patterns. The white-eye locus in Drosophila was the rst case when a locus was assigned to the X chromosome. Over four hundred sex-linked loci are now known in human beings. STUDY OBJECTIVE 4: To use pedigrees to infer inheriSTUDY OBJECTIVE 2: To understand methods of dosage
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mination in various organisms
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Sex determination in animals is often based on chromosomal differences. In human beings and fruit ies, females are homogametic (XX) and males are heterogametic (XY). In human beings, a locus on the Y chromosome, SRY, determines maleness; in Drosophila, sex is determined by the balance between genes on the X chromosome and genes on the autosomes that regulate the state of the sex-switch gene, Sxl.
tance patterns 97 102
Human genetic studies use pedigree analysis to determine inheritance patterns because it is impossible to carry out largescale, controlled human crosses. However, not all traits determined by genotype are apparent in the phenotype, and this lack of penetrance can pose problems in genetic analysis.
compensation
90 95
Different organisms have different ways of solving problems of dosage compensation for loci on the X chromosome. In human beings, one of the X chromosomes in cells in a woman is Lyonized, or inactivated. Lyonization in women leads to cellu-
S O L V E D
PROBLEM 1: A Female fruit y with a yellow body is dis-
P R O B L E M S
yellow-bodied and the females are wild-type. When these ies are crossed among themselves, the F2 produced are both yellow-bodied and wild-type, equally split among males and females (see g. 1). Explain the genetic control of this trait. Answer: Since the results in the F1 generation differ between the two sexes, we suspect that a sex-linked locus is responsible for the control of body color. If we assume that it is a recessive trait, then the female parent must have been a recessive homozygote, and the male must have been a wild-type hemizygote. If we assign the wild-type allele as X , the yellow-body allele as Xy, and the Y chromosome as Y, then gure 1, showing the crosses into the F2 generation, is consistent with the data.Thus, a recessive Xlinked gene controls yellow body color in fruit ies.
PROBLEM 2: The affected individuals in the pedigree in gure 2 are chronic alcoholics (data from the National Institute of Alcohol Abuse and Alcoholism). What can you say about the inheritance of this trait Answer: We begin by assuming 100% penetrance. If that is the case, then we can rule out either sex-linked or autosomal recessive inheritance because both parents had the trait, yet they produced some unaffected children.
covered in a wild-type culture.The female is crossed with a wild-type male. In the F1 generation, the males are
Yellow Xy Xy
Wild-type X+ Y
X+ F1
Y Xy Y Yellow(
Xy X+ Wild-type&
Xy X+ F2 Xy X+ Wild-type& Xy Xy Yellow&
Y X+ Y Wild-type( Xy Y Yellow(
Cross between yellow-bodied and wild-type fruit ies.
Tamarin: Principles of Genetics, Seventh Edition
II. Mendelism and the Chromosomal Theory
5. Sex Determination, Sex Linkage, and Pedigree Analysis
The McGraw Hill Companies, 2001
Five
Sex Determination, Sex Linkage, and Pedigree Analysis
II 1 Figure 2 2 3 4 5 6 7 8 9 10
A pedigree for alcoholism.
Nor can the mode of inheritance be by a sex-linked dominant gene because an affected male would have only affected daughters, since his daughters get copies of his single X chromosome. We are thus left with autosomal dominance as the mode of inheritance. If that is the case, then both parents must be heterozygotes; otherwise, all the children would be affected. If both parents are heterozygotes, we expect a 3:1 ratio of affected to unaffected offspring (a cross of Aa Aa produces offspring of A-:aa in a 3:1 ratio); here, the ratio is 6:4. If we did a chi-square test, the expected numbers would be 7.5:2.5 (3/4 and 1/4, respectively, of 10). Although the expected value of 2.5 makes it inappropriate to do a chi-square test (the expected value is too small), we can see that the observed and expected numbers are very close. Thus, from the pedigree we would conclude that an autosomal dominant allele controls chronic alcoholism. (Although the analysis is consistent, we actually cannot draw that conclusion about alcoholism because other pedigrees are not consistent with 100% penetrance, a one-gene model, or the lack of environmental in uences. In fact, scientists are currently debating whether alcoholism is inherited at all. These types of problems related to complex human traits are discussed in chapter 18.)
PROBLEM 3: A female y with orange eyes is crossed with a male y with short wings. The F1 females have wild-type (red) eyes and long wings; the F1 males have orange eyes and long wings.The F1 ies are crossed to yield
47 long wings, red eyes 45 long wings, orange eyes 17 short wings, red eyes 14 short wings, orange eyes with no differences between the sexes. What is the genetic basis of each trait Answer: In the F1 ies, we see a difference in eye color between the sexes, indicating some type of sex linkage. Since the females are wild-type, wild-type is probably dominant to orange. We can thus diagram the cross for eye color as (female) XoXo orange X Xo red X Xo XoXo red orange Z Z X Y red X Y (male) red XoY orange XoY orange P1
We would thus expect to see equal numbers of redeyed and orange-eyed males and females, which is what we observe. Now look at long versus short wings. If we disregard eye color, wing length seems to be under autosomal control with short wings being recessive.Thus, the parents are homozygotes (ss and s s ), the F1 offspring are heterozygotes (s s), and the F2 progeny have a phenotypic ratio of 3:1, wild-type (long) to short wings.
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