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Homework for Wednesday, Jan 30 • P. 285: problems 4 and 7 • In Student Study Guide: – Interactive questions: 15.2, 15.3, 15.4 – Test your Knowledge:2, 6, 7, 20 You get 5 minutes to prepare for the class answers to one of the following.Teams of 2-3: • 1.What is the Chromosome theory of inheritance? • 2. Distinguish between “wild-type”; “mutant” phenotypes, and give an example • 3. Where are the red/white eye alleles located in fruit flies? What did Morgan discover?……. • 4. explain Fig. 15.3 • 5. Distinguish between sex-linked genes and linked genes. • 6. What is Genetic recombination? • 7. Refer to Fig. 15.4-give the phenotype of the wild-type female, and the double mutant male (draw on board) CHAPTER 15 THE CHROMOSOMAL BASIS OF INHERITANCE Section A: Relating Mendelism to Chromosomes 1. Mendelian inheritance has its physical basis in the behavior of chromosomes during sexual life cycles 2. Morgan traced a gene to a specific chromosome 3. Linked genes tend to be inherited together because they are located on the same chromosome 4. Independent assortment of chromosomes and crossing over produce genetic recombinants 5. Geneticists use recombination data to map a chromosome’s Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings genetic loci The Chromosomal Theory of Inheritance • Genes have specific loci on chromosomes and it is the chromosomes that undergo segregation and independent assortment 2. Morgan traced a gene to a specific chromosome • Thomas Hunt Morgan was the first to associate a specific gene with a specific chromosome • early 20th century. • Drosophila melanogaster, a fruit fly species that eats fungi on fruit. – prolific breeders – generation time of two weeks. – Fruit flies have three pairs of autosomes and a pair of sex chromosomes (XX in females, XY in – Morgan discovered a single male fly with white eyes instead of the usual red. • wild type: the normal or most frequently observed phenotype • mutant phenotypes: Alternatives Fig. 15.2 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • White Eyed Male x Red-eyed female offspring • F1 offspring X F1 the F2 offspring. all red eyed classic 3:1 phenotypic ratio in • Surprisingly, the white-eyed trait appeared only in males. – All the females and half the males had red eyes. • Morgan concluded that a fly’s eye color was linked to its sex. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Morgan deduced that – eye color is linked to sex AND – the gene for eye color is only located on the X chromosome. – Sex-Linked Genes Fig. 15.3 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Linked Genes • linked genes: Genes located on the same chromosome. • They tend to be inherited together because the chromosome is passed along as a unit. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Figure 15.4 Evidence for linked genes in Drosophila Figure 15.5a Recombination due to crossing over Genetic Recombination • Production of offspring with new combos of traits different from those combos found in the parents • Parental types • Recombinants • Recombinant frequency (# recombinants/total offspring)100 • 1 map unit = 1% recombinant frequency Genetic recombination: • Can result from: • 1. Independent assortment of chromosomes (the recombination of unlinked genes). 2. crossing over ( the recombination of linked genes) Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Figure 15.5b Recombination due to crossing over Recombinant Frequency Problem • A wild type fruit fly (heterozygous for gray body color and red eyes) • was mated with a black fruit fly with purple eyes. • What is the recombinant frequency for these genes? • Wild type – 721 • Black purple – 751 • Gray purple – 49 • Black red - 45 Recombinant Frequency Problem - Answer • Total offspring - 1566 • Parental types – 1472 • Recombinants – 94 • Frequency = 94/1566 *100 = 6.0% Recap-Morgan’s test-cross (2 traits) • Most of the F2 offspring looked like the parents( because the genes were linked-same chromosome) • Explaining why the were greater number of recombinant phenotypes (resulted from some other force of nature-----crossing over) Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings – Under independent assortment (genes not linked) the testcross should produce a 1:1:1:1 phenotypic ratio. – If completely linked, we should expect to see a 1:1:0:0 ratio with only parental phenotypes among offspring. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings 5. Mapping chromosomes • Alfred Sturtevant • Linkage map: a genetic map (GENES & THEIR RELATIVE LOCTIONS) based upon recombination frequencies. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • The farther apart two genes are, the higher the probability that a crossover will occur between them & therefore a higher recombination frequency. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • A linkage map provides an imperfect picture of a chromosome. – Map units indicate relative distance and order, not precise locations of genes. • Cytological maps. – These indicated the positions of genes with respect to chromosomal features.-like banding Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings three fruit fly genes, body color (b), wing size (vg), and eye color (cn). – The recombination frequency between cn and b is 9%. – The recombination frequency between cn and vg is 9.5%. – The recombination frequency between b and vg is 17% Fig. 15.6 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Map units: the distance between genes • 1 map unit =1% recombination frequency • Centimorgan • relative distance and order, not precise locations of genes. –. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Practice: Interactive Question 15.2 from student work book • Recombination frequencies for gene pairs. Create linkage map, show map units between gene loci. • J,k 12% • J,m 9% • K,l 6% • l,m 15% answer K L 6 J 6 M 9 • Some genes on a chromosome are so far apart that a crossover between them is virtually certain. • Frequency of recombination reaches has a maximum value of 50% • Same as recom. Freq. as if found on separate chromosomes, and are inherited independently. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Homework for Wednesday, Jan 30 • P. 285: problems 4 and 7 • In Student Study Guide: – Interactive questions: 15.2, 15.3, 15.4 – Test your Knowledge:2, 6, 7, 20 CHAPTER 15 THE CHROMOSOMAL BASIS OF INHERITANCE Section B: Sex Chromosomes 1. The chromosomal basis of sex varies with the organism 2. Sex-linked genes have unique patterns of inheritance Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings The chromosomal basis of sex varies with the organism 1. In the X-Y system, X and Y rarely undergo crossing over. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • 2. X-0 system – some insects: – XX=female; XO-male • Z-W system – Birds: – females determine sex ZZ-male; ZW-females • the haplo-diploid system: – Bees, ants: no sex chromosomesFemales develop from fertilized eggs (2n); Males from unfert. eggs (haploid) Fig. 15.8 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • In humans, the anatomical signs of sex first appear when the embryo is about two months old. • In individuals with the SRY gene (sexdetermining region of the Y chromosome), the generic embryonic gonads are modified into testes. – Activity of the SRY gene triggers a cascade of biochemical, physiological, and anatomical features because it regulates many other genes. – In addition, other genes on the Y chromosome are necessary for the production of functional sperm. • In individuals lacking the SRY gene, the generic embryonic gonads develop into ovaries. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings The Chromosomal Basis of Sex in Humans • Males-heterogametic (XY) • Females homogametic ( XX) • Whether an embryo develops into male of female depends upon the Y chromosome. • SRY gene – Triggers cascade of events—normal testicular development – SRY absent-gonads develop into ovaries 2. Sex-linked genes have unique patterns of inheritance Fig. 15.9 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Sex-linked traits • Males are hemizygous –More males than females have sex-linked disorders • Sex-linked disorders • 1. Duchenne muscular dystrophy affects one in 3,500 males born in the United States. – rarely live past their early 20s. – This disorder is due to the absence of an X-linked gene for a key muscle protein, called dystrophin. – progressive weakening of the muscles and a loss of coordination. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • 2.Hemophilia sex-linked, recessive absence of one or more clotting factors that normally slow and then stop bleeding. • prolonged bleeding – Bleeding in muscles and joints can be painful and lead to serious damage. – treated with intravenous injections of the missing protein. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Sex Linkage Problem Hemophilia is caused by a sex-linked recessive allele. A man with hemophilia marries a woman with normal clotting factors. What is the probability that they will have a daughter with hemophilia? What is the probability that they will have a son with hemophilia? What is the probability that their son will have hemophilia? X-Inactivation in Females Compensating for the missing X. Lyon Hypothesis: In female mammals, only one X is fully functional • Barr body –Inactive X chromosome (random) –condenses –Reactivated in gonadal cells at meiosis • Mosaic of inactive maternal and paternal X chromosomes (calico cats) • In humans, this mosaic pattern is evident in women who are heterozygous for a X-linked mutation that prevents the development of sweat glands. – A heterozygous woman will have patches of normal skin and skin patches lacking sweat glands. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Similarly, the orange and black pattern on tortoiseshell cats is due to patches of cells expressing an orange allele while others have a nonorange allele. Fig. 15.10 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Figure 15.10x Calico cat X-inactivation Produces Tortoiseshell Cats • X-linked system with two alleles – heterozygous females express both alleles in a mosaic pattern, depending on active gene CHROMOSOMAL BASIS OF INHERITANCE: ERRORS AND EXCEPTIONS Nondisjunction and Abnormal Chromosome Numbers • aneuploidy (an abnormal chromosome number) – normal gamete fuses with a gamete from a nondisjunction (effect usually severe) – trisomic 2n + 1 total chromosomes – monosomic 2n - 1 chromosomes. • Nondisjunction spindle incorrectly separates chromosome during karyokinesis • usually lethal Polypoidy • organisms with more than two complete sets of chromosomes (effect often less severe) • usually occurs when a normal gamete fertilizes another gamete in which there has been nondisjunction of all its chromosomes – produces a triploid (3n) zygote (2n + 1n) Polyploid is Common in Plants, but Rare in Animals • polyploidy plays an important role in the evolution of plants – economically important – at least one species of rodent may be a product of polyploidy • Polyploids are more nearly • normal in phenotype than Abnormal Chromosome Numbers and Human Disorders • most aneuploid zygotes are non-viable, and spontaneously abort early in development – developmental problems result from an imbalance among gene products • certain aneuploid conditions upset the balance less, survive to term and beyond – individuals have a set of symptoms - a syndrome - characteristic of the type of Down Syndrome • trisomy 21, three copies of chromosome 21 – affects one in 700 children born in U.S. • severely alters an individual’s phenotype in specific ways. Incidence of Trisomy Increases with Age in Women • usually result from nondisjunction during gamete production in one parent • frequency of Down syndrome correlates with age of mother – may be linked to some age-dependent abnormality in spindle checkpoint during meiosis I, leading to nondisjunction • incidence of other trisomies also increase with maternal age, but are usually lethal if autosomal Nondisjunction of Sex Chromosomes • produces a variety of viable aneuploid conditions in humans • unlike autosomes, aneuploidy in sex chromosomes upsets genetic balance less severely. – may be because Y chromosome contains relatively few genes – extra copies of X chromosome become inactivated as Barr bodies in somatic cells XX or XY Nondisjuntions • XXY males Klinefelter’s syndrome, (1/2000) – sterile individuals with male sex organs – may be feminized. They are of normal intelligence • XYY males often taller than average • XXX females Trisomy X (1/2000) – produces healthy females • XO females Turner’s syndrome (1/5000) – produces phenotypic, but immature females Structural Changes in Chromosomes Breakage of a chromosome can lead to four types of changes in chromosome structure. • 1. A deletion occurs when a chromosome fragment lacking a centromere is lost during cell division. -Usually lethal • 2. A duplication occurs when a fragment becomes attached as an extra segment to a sister chromatid. Fig. 15.13a & b Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • 3. An inversion occurs when a chromosomal fragment reattaches to the original chromosome but in the reverse orientation. • 4. In translocation, a chromosomal fragment joins a nonhomologous chromosome. – Some translocations are reciprocal, others are not. Fig. 15.13c & d Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Deletions and duplications are common in meiosis. – Homologous chromatids may break and rejoin at incorrect places, such that one chromatid will lose more genes than it receives. •. – Duplications and translocations are typically harmful. • Reciprocal translocation or inversion can alter phenotype because a gene’s expression is influenced by its location. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Structural Changes and Human Disorders • cri du chat syndrome caused by a specific deletion in chromosome 5 – mentally handicapped, small head, unusual facial features, cry sounds like the meowing of a distressed cat. – fatal in infancy or early childhood • chronic myelogenous leukemia (CML) – CML translocation between tips of chromosome 22 and chromosome 9 2. Phenotypic imprinting • effects of some mammalian genes depends on whether they were inherited from mother or father • alleles for most genes have same expression regardless of source (maternal or paternal) • expression of some traits in mammals, vary depending on origin of inherited alleles. – genes involved are not linked to sex and may or may not lie on the X Prader-Willi and Angelman Syndromes • both due to a deletion of a specific segment of chromosome 15 • different phenotypic effects are due to genomic imprinting – Prader-Willi syndrome, mental retardation, obesity, short stature, and unusually small hands and feet • abnormal chromosome from their father. – Angelman syndrome, spontaneous laughter, jerky movements, and other motor and mental symptoms Fragile X Syndrome • leads to various degrees of mental retardation, appears to be subject to genomic imprinting. – abnormal X chromosome in which tip hangs on by a thin thread of DNA. – disorder affects 1/1,500 males and 1/2,500 females • inheritance of fragile X is complex • syndrome is more common when abnormal chromosome is inherited from mother Genomic Imprinting • a gene on one homologous chromosome is silenced, other is expressed • imprinting status of a given gene depends on whether gene resides in a female or a male – effects of alleles on offspring, depend on whether they arrive in zygote via ovum or via sperm • silencing mechanism depends on presence or absence of methylation, not well understood Genomic Imprinting is Reset Each Generation • each new generation, all imprints are “erased” in gamete-producing cells. • chromosomes are all “reimprinted” according to individuals sex • Certain aneuploid conditions upset the balance less, leading to survival to birth and beyond. – These individDevelopmental problems result from an imbalance among gene products. – These individuals have a set of symptoms - a syndrome characteristic of the type of aneuploidy. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Chromosomal translocations • Some individuals with Down syndrome have the normal number of chromosomes but have all or part of a third chromosome 21 attached to another chromosome by translocation. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings 2. The phenotypic effects of some mammalian genes depend on whether they were inherited from the mother or the father (imprinting) • For most genes it is a reasonable assumption that a specific allele will have the same effect regardless of whether it was inherited from the mother or father. • However, for some traits in mammals, it does depend on which parent passed along the alleles for those traits. – The genes involved are not sex linked and may or may not lie on the X chromosome. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Two disorders with different phenotypic effects, Prader-Willi syndrome and Angelman syndrome, are due to the same cause, a deletion of a specific segment of chromosome 15. – Prader-Willi syndrome is characterized by mental retardation, obesity, short stature, and unusually small hands and feet. – These individuals inherit the abnormal chromosome from their father. – Individuals with Angelman syndrome exhibit spontaneous laughter, jerky Copyrightmovements, © 2002 Pearson Education, Inc., publishing as Benjamin Cummingsmotor and mental and other • The difference between the disorders is due to genomic imprinting. • In this process, a gene on one homologous chromosome is silenced, while its allele on the homologous chromosome is expressed. • The imprinting status of a given gene depends on whether the gene resides in a female or a male. – The same alleles may have different effects on offspring, depending on whether they arrive in the zygote via the ovum or via the sperm. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • In the new generation, both maternal and paternal imprints are apparently “erased” in gamete-producing cells. • Then, all chromosomes are reimprinted according to the sex of the individual in which they reside. Fig. 15.15 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Fragile X syndrome, which leads to various degrees of mental retardation, also appears to be subject to genomic imprinting. – This disorder is named for an abnormal X chromosome in which the tip hangs on by a thin thread of DNA. – This disorder affects one in every 1,500 males and one in every 2,500 females. • Inheritance of fragile X is complex, but the syndrome is more common when the abnormal chromosome is inherited from the mother. – This is consistent with the higher frequency in – Imprinting by the mother somehow causes it. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings males. 3. Extranuclear genes exhibit a nonMendelian pattern of inheritance • Not all of a eukaryote cell’s genes are located in the nucleus. • Extranuclear genes are found on small circles of DNA in mitochondria and chloroplasts. • These organelles reproduce themselves. • Their cytoplasmic genes do not display Mendelian inheritance. – They are not distributed to offspring Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Karl Correns first observed cytoplasmic genes in plants in 1909. • He determined that the coloration of the offspring was determined only by the maternal parent. • These coloration patterns are due to genes in the plastids which are inherited only via the ovum, not the pollen. Fig. 15.16 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Because a zygote inherits all its mitochondria only from the ovum, all mitochondrial genes in mammals demonstrate maternal inheritance. • Several rare human disorders are produced by mutations to mitochondrial DNA. – These primarily impact ATP supply by producing defects in the electron transport chain or ATP synthase. – Tissues that require high energy supplies (for example, the nervous system and Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings