In addition to the predominant adult hemoglobin,HbA, which contains two α-globin chains and twoβ-globin chains (α2β2), there is a minor hemoglobin,HbA2, composed of two α and two δ chains (α2δ2).The β- and δ-globin genes are arranged in tandem andare highly homologous. Draw the chromosomes thatwould result from an event of unequal crossing-overbetween the β and δ genes
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In addition to the predominant adult hemoglobin,
HbA, which contains two α-globin chains and two
β-globin chains (α2β2), there is a minor hemoglobin,
HbA2, composed of two α and two δ chains (α2δ2).
The β- and δ-globin genes are arranged in tandem and
are highly homologous. Draw the chromosomes that
would result from an event of unequal crossing-over
between the β and δ genes
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- Adult hemoglobin is a multimeric protein with fourpolypeptides, two of which are α-globin and two ofwhich are β-globin.a. How many genes are needed to define the structureof the hemoglobin protein?b. If a person is heterozygous for wild-type allelesand alleles that would yield amino acid substitutionvariants for both α-globin and β-globin, how manydifferent kinds of hemoglobin protein would befound in the person’s red blood cells and in whatproportion? Assume all alleles are expressed at thesame level.A female patient 19 years old, whose symptoms areanemia and internal bleeding due to a massive buildupof leukemic white blood cells, is diagnosed withchronic myelogenous leukemia (CML). Karyotypeanalysis shows that the leukemic cells of this patientare heterozygous for a reciprocal translocation involving chromosomes 9 and 22. However, none of thenormal, nonleukemic cells of this patient contain thetranslocation. Which of the following statements istrue and which is false?a. The translocation results in the inactivation (loss offunction) of a tumor-suppressor gene.b. The translocation results in the inactivation (loss offunction) of an oncogene.c. There is a 50% chance that any child of this patientwill have CML.d. This patient is a somatic mosaic in terms of thekaryotype.e. DNA extracted from leukemic cells of this patient,if taken up by normal mouse tissue culture cells,could potentially transform the mouse cells intocells capable of causing tumors.f. The normal function of the…The HbβS(sickle-cell) allele of the human β-globingene changes the sixth amino acid in the β-globinchain from glutamic acid to valine. In HbβC, the sixthamino acid in β-globin is changed from glutamic acidto lysine. What would be the order of these two mutations within the map of the β-globin gene?
- Ehler-Danlos syndrome is a rare disorder caused by a mutation ina gene that encodes a protein called collagen (type 3 A1). Collagenis found in the extracellular matrix that plays an important role inthe formation of skin, joints, and other connective tissues. Peoplewith Ehler-Danlos syndrome have extraordinarily flexible skin andvery loose joints. The following pedigree contains several individualsaffected with this syndrome, shown with black symbols. Basedon this pedigree, does the syndrome follow autosomal recessive,autosomal dominant, X-linked recessive, or X-linked dominantinheritance? Explain your reasoning.Hemophilia A is caused by a sex-linked recessive gene in human and in dogs. a. What proportions (and sexes), among their offspring will be hemophiliacs if a hemophilic male is mated to a homozygous nonhemophilic female?b. If a daughter produced by the mating in (a) is mated to a normal male, what proportions and (sexes) will be hemophilic among their offspring?Spherocytosis is an inherited blood disease in whichthe erythrocytes (red blood cells) are spherical insteadof biconcave. This condition can be inherited in adominant fashion, with ANK1 (the nonfunctional mutant allele) dominant to ANK1+. In people with spherocytosis, the spleen recognizes the spherical redblood cells as defective and removes them from thebloodstream, leading to anemia. The spleen in different people removes the spherical erythrocytes withdifferent efficiencies. Some people with sphericalerythrocytes suffer severe anemia and some mild anemia, yet others have spleens that function so poorly nosymptoms of anemia exist at all. When 2400 peoplewith the genotype ANK1 ANK1+ were examined, itwas found that all of them had spherical erythrocytes,2250 had anemia of varying severity, and 150 had nosymptoms. (Assume that ANK1 ANK1 homozygotesdo not exist.)a. Does this description of people with spherocytosisrepresent incomplete penetrance, variable expressivity, or both? Explain…
- In com, male sterility is controlled by maternal cytoplasmic elements. However, the presence of a nuclear fertility restorer gene (F_) restores fertility to male sterile lines. a. What are the crosses male sterile female x FF male? Give the genotypes and phenotypes of the offspring in each cross. Explain.The pedigree here shows the inheritance of a human disease knownas familial hypercholesterolemia. This disorder is characterized by an elevated level of serumcholesterol in the blood. Though relatively rare, this geneticabnormality can be a contributing factor to heart attacks. At themolecular level, this disease is caused by a defective gene thatencodes a protein called low-density lipoprotein receptor (LDLR).In the bloodstream, serum cholesterol is bound to a carrier proteinknown as low-density lipoprotein (LDL). LDL binds to LDLR,which enables cells to absorb cholesterol. When LDLR is defective,it becomes more difficult for the cells to absorb cholesterol. Thisexplains why the blood level of cholesterol remains high. Basedon the pedigree, what is the most likely pattern of inheritance ofthis disorder?Sickle-cell anemia is a recessive autosomal disorderthat is caused by an amino acid substitution in theβ-hemoglobin protein. The DNA mutation underlyingthis substitution is a SNP that alters a GAG codon forthe amino acid glutamate to a GTG that codes a valine.The frequency of sickle-cell anemia among AfricanAmericans is about 1/400. What is the frequency ofthis GTG codon in the β-hemoglobin gene amongAfrican Americans?
- The chromosome 9/22 translocation associated withCML (chronic myelogenous leukemia) is called thePhiladelphia chromosome after the city in which itscancer association was first discovered in 1960.People with CML do not inherit this translocation—it occurs in somatic cells. Why do you think that thisparticular translocation that fuses the bcr and ablgenes happens independently in the somatic cellsof many different people?A rare blinding disease that has a relation to dengenerative factors is partially penetrant. In the following pedigrees for two families, the affected symptomatic individuals (black circles and squares) have been diagnosed with this disease due to the mutation in mitochondrial DNA m.14484T>C. If III.4 is homoplasmic for m.14484T>C in hair, blood, urine and other tissues examined. What will occur with IV.7 then?Ehler-Danlos syndrome is a rare disorder caused by a mutation ina gene that encodes a protein called collagen (type 3 A1). Collagenis found in the extracellular matrix that plays an important role inthe formation of skin, joints, and other connective tissues. Peoplewith Ehler-Danlos syndrome have extraordinarily flexible skin and very loose joints. The pedigree below contains several individualsaffected with this syndrome, shown with black symbols. Based onthis pedigree, does the syndrome appear to follow autosomalrecessive, autosomal dominant, X-linked recessive, or X-linkeddominant inheritance? Explain your reasoning.