Chromosomes and Human Genetics Chapter 12 Chromosomes Cancer

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Chromosomes and Human Genetics Chapter 12

Chromosomes and Human Genetics Chapter 12

Chromosomes & Cancer n n n Some genes on chromosomes control cell growth and

Chromosomes & Cancer n n n Some genes on chromosomes control cell growth and division If something affects chromosome structure at or near these loci, cell division may spiral out of control This can lead to cancer

Philadelphia Chromosome n First abnormal chromosome to be associated with a cancer n Reciprocal

Philadelphia Chromosome n First abnormal chromosome to be associated with a cancer n Reciprocal translocation n Causes chronic myelogenous leukemia (CML)

Genes n n n Units of information about heritable traits In eukaryotes, distributed among

Genes n n n Units of information about heritable traits In eukaryotes, distributed among chromosomes Each has a particular locus n Location on a chromosome

Homologous Chromosomes n n n Homologous autosomes are identical in length, size, shape, and

Homologous Chromosomes n n n Homologous autosomes are identical in length, size, shape, and gene sequence Sex chromosomes are nonidentical but still homologous Homologous chromosomes interact, then segregate from one another during meiosis

Alleles n Different molecular forms of a gene n Arise through mutation n Diploid

Alleles n Different molecular forms of a gene n Arise through mutation n Diploid cell has a pair of alleles at each locus n Alleles on homologous chromosomes may be same or different

Sex Chromosomes n Discovered in late 1800 s n Mammals, fruit flies n XX

Sex Chromosomes n Discovered in late 1800 s n Mammals, fruit flies n XX is female, XY is male n In other groups XX is male, XY female n Human X and Y chromosomes function as homologues during meiosis

Karyotype Preparation Stopping the Cycle n n Cultured cells are arrested at metaphase by

Karyotype Preparation Stopping the Cycle n n Cultured cells are arrested at metaphase by adding colchicine This is when cells are most condensed and easiest to identify

Karyotype Preparation n n Arrested cells are broken open Metaphase chromosomes are fixed and

Karyotype Preparation n n Arrested cells are broken open Metaphase chromosomes are fixed and stained Chromosomes are photographed through microscope Photograph of chromosomes is cut up and arranged to form karyotype diagram

Karyotype Diagram 1 12 2 3 4 13 14 15 16 5 17 6

Karyotype Diagram 1 12 2 3 4 13 14 15 16 5 17 6 7 8 9 18 19 20 21 10 22 11 XX (or XY) Figure 12. 4 Page 197

Sex Determination Figure 12. 5 Page 198 female (XX) male (XY) eggs sperm X

Sex Determination Figure 12. 5 Page 198 female (XX) male (XY) eggs sperm X x Y X x X X XX XX Y XY XY

The Y Chromosome n n Fewer than two dozen genes identified One is the

The Y Chromosome n n Fewer than two dozen genes identified One is the master gene for male sex determination n SRY gene (sex-determining region of Y) n SRY present, testes form n SRY absent, ovaries form

The X Chromosome n Carries more than 2, 300 genes n Most genes deal

The X Chromosome n Carries more than 2, 300 genes n Most genes deal with nonsexual traits n Genes on X chromosome can be expressed in both males and females

Discovering Sex Linkage homozygous dominant female recessive male x Gametes: X X X Y

Discovering Sex Linkage homozygous dominant female recessive male x Gametes: X X X Y All F 1 have red eyes Gametes: x X X 1/2 1/4 1/2 F 2 generation: X 1/4 1/4 Figure 12. 7 Page 200 1/2 Y

Crossover Frequency Proportional to the distance that separates genes A B C D Crossing

Crossover Frequency Proportional to the distance that separates genes A B C D Crossing over will disrupt linkage between A and B more often than C and D In-text figure Page 201

Linkage Mapping in Humans n n Linkage maps based on pedigree analysis through generations

Linkage Mapping in Humans n n Linkage maps based on pedigree analysis through generations Color blindness and hemophilia are very closely linked on X chromosome

Pedigree Symbols male female marriage/mating offspring in order of birth, from left to right

Pedigree Symbols male female marriage/mating offspring in order of birth, from left to right Individual showing trait being studied sex not specified I, III, IV. . . Figure 12. 9 a Page 202 generation

Pedigree for Polydactyly female II 5, 5 6, 6 * III IV 6 5,

Pedigree for Polydactyly female II 5, 5 6, 6 * III IV 6 5, 5 6, 6 7 5, 5 6, 6 5, 5 6, 6 5, 6 6, 7 12 V *Gene not expressed in this carrier. Figure 12. 9 b Page 202 5, 5 6, 6

Genetic Abnormality n A rare, uncommon version of a trait n Polydactyly n Unusual

Genetic Abnormality n A rare, uncommon version of a trait n Polydactyly n Unusual number of toes or fingers n Does not cause any health problems n View of trait as disfiguring is subjective

Genetic Disorder n n Inherited conditions that cause mild to severe medical problems Why

Genetic Disorder n n Inherited conditions that cause mild to severe medical problems Why don’t they disappear? n n Mutation introduces new rare alleles In heterozygotes, harmful allele is masked, so it can still be passed on to offspring

Autosomal Recessive Inheritance Patterns n If parents are both heterozygous, child will have a

Autosomal Recessive Inheritance Patterns n If parents are both heterozygous, child will have a 25% chance of being affected Figure 12. 10 a Page 204

Galactosemia n n Caused by autosomal recessive allele Gene specifies a mutant enzyme in

Galactosemia n n Caused by autosomal recessive allele Gene specifies a mutant enzyme in the pathway that breaks down lactose enzyme 1 lactose In-text figure Page 204 enzyme 3 enzyme 2 galactose + glucose galactose-1 phosphate intermediate in glycolysis

Autosomal Dominant Inheritance Trait typically appears in every generation Figure 12. 10 b Page

Autosomal Dominant Inheritance Trait typically appears in every generation Figure 12. 10 b Page 204

Huntington Disorder n n Autosomal dominant allele Causes involuntary movements, nervous system deterioration, death

Huntington Disorder n n Autosomal dominant allele Causes involuntary movements, nervous system deterioration, death Symptoms don’t usually show up until person is past age 30 People often pass allele on before they know they have it

Achondroplasia n n Autosomal dominant allele In homozygous form usually leads to stillbirth Heterozygotes

Achondroplasia n n Autosomal dominant allele In homozygous form usually leads to stillbirth Heterozygotes display a type of dwarfism Have short arms and legs relative to other body parts

X-Linked Recessive Inheritance n n Males show disorder more than females Son cannot inherit

X-Linked Recessive Inheritance n n Males show disorder more than females Son cannot inherit disorder from his father Figure 12. 12 a Page 205

Examples of X-Linked Traits n Color blindness n n Inability to distinguish among some

Examples of X-Linked Traits n Color blindness n n Inability to distinguish among some of all colors Hemophilia n Blood-clotting disorder n 1/7, 000 males has allele for hemophilia A n Was common in European royal families

Fragile X Syndrome n An X-linked recessive disorder n Causes mental retardation n n

Fragile X Syndrome n An X-linked recessive disorder n Causes mental retardation n n Mutant allele for gene that specifies a protein required for brain development Allele has repeated segments of DNA

Hutchinson-Gilford Progeria n Mutation causes accelerated aging n No evidence of it running in

Hutchinson-Gilford Progeria n Mutation causes accelerated aging n No evidence of it running in families n Appears to be dominant n Seems to arise as spontaneous mutation n Usually causes death in early teens

Duplication n Gene sequence that is repeated several to hundreds of times n Duplications

Duplication n Gene sequence that is repeated several to hundreds of times n Duplications occur in normal chromosomes n May have adaptive advantage n Useful mutations may occur in copy

Duplication normal chromosome one segment repeated three repeats

Duplication normal chromosome one segment repeated three repeats

Inversion A linear stretch of DNA is reversed within the chromosome segments G, H,

Inversion A linear stretch of DNA is reversed within the chromosome segments G, H, I become inverted In-text figure Page 206

Translocation n A piece of one chromosome becomes attached to another nonhomologous chromosome Most

Translocation n A piece of one chromosome becomes attached to another nonhomologous chromosome Most are reciprocal Philadelphia chromosome arose from a reciprocal translocation between chromosomes 9 and 22

Translocation one chromosome a nonhomologous chromosome nonreciprocal translocation In-text figure Page 206

Translocation one chromosome a nonhomologous chromosome nonreciprocal translocation In-text figure Page 206

Deletion n n Loss of some segment of a chromosome Most are lethal or

Deletion n n Loss of some segment of a chromosome Most are lethal or cause serious disorder

Aneuploidy n n Individuals have one extra or less chromosome (2 n + 1

Aneuploidy n n Individuals have one extra or less chromosome (2 n + 1 or 2 n - 1) Major cause of human reproductive failure Most human miscarriages are aneuploids

Polyploidy n Individuals have three or more of each type of chromosome (3 n,

Polyploidy n Individuals have three or more of each type of chromosome (3 n, 4 n) n Common in flowering plants n Lethal for humans n 99% die before birth n Newborns die soon after birth

Nondisjunction n+1 n-1 chromosome alignments at metaphase I n-1 nondisjunction alignments at at anaphase

Nondisjunction n+1 n-1 chromosome alignments at metaphase I n-1 nondisjunction alignments at at anaphase I metaphase II anaphase II Figure 12. 17 Page 208

Down Syndrome n n Trisomy of chromosome 21 Mental impairment and a variety of

Down Syndrome n n Trisomy of chromosome 21 Mental impairment and a variety of additional defects Can be detected before birth Risk of Down syndrome increases dramatically in mothers over age 35

Turner Syndrome n Inheritance of only one X (XO) n 98% spontaneously aborted n

Turner Syndrome n Inheritance of only one X (XO) n 98% spontaneously aborted n Survivors are short, infertile females n No functional ovaries n Secondary sexual traits reduced n May be treated with hormones, surgery

Klinefelter Syndrome n n n XXY condition Results mainly from nondisjunction in mother (67%)

Klinefelter Syndrome n n n XXY condition Results mainly from nondisjunction in mother (67%) Phenotype is tall males Sterile or nearly so n Feminized traits (sparse facial hair, somewhat enlarged breasts) n Treated with testosterone injections n

XYY Condition n Taller than average males n Most otherwise phenotypically normal n Some

XYY Condition n Taller than average males n Most otherwise phenotypically normal n Some mentally impaired n Once thought to be predisposed to criminal behavior, but studies now discredit

Phenotypic Treatments n Symptoms of many genetic disorders can be minimized or suppressed by

Phenotypic Treatments n Symptoms of many genetic disorders can be minimized or suppressed by n Dietary controls n Adjustments to environmental conditions n Surgery or hormonal treatments

Genetic Screening n n Large-scale screening programs detect affected persons Newborns in United States

Genetic Screening n n Large-scale screening programs detect affected persons Newborns in United States routinely tested for PKU n Early detection allows dietary intervention and prevents brain impairment

Prenatal Diagnosis n Amniocentesis n Chorionic villus sampling n Fetoscopy n All methods have

Prenatal Diagnosis n Amniocentesis n Chorionic villus sampling n Fetoscopy n All methods have some risks

Preimplantation Diagnosis n Used with in-vitro fertilization n Mitotic divisions produce ball of 8

Preimplantation Diagnosis n Used with in-vitro fertilization n Mitotic divisions produce ball of 8 cells n All cells have same genes n n One of the cells is removed and its genes analyzed If cell has no defects, the embryo is implanted in uterus