Chromosomes and Human Genetics Chapter 12

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

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

Studying Human Genetics Studying Human Genetics is much more complicated than using other model systems (e.g. Pea Plants) Humans reproduce slowly, have few offspring, and it is unethical to breed humans for experiments There are many techniques that are used to study human genetics indirectly Karyotypes Pedigree analysis Linkage maps

Karyotype Picture of an individual’s chromosomes Making a Karyotype: Metaphase chromosomes are fixed and stained Chromosomes are photographed through microscope Photograph of chromosomes is cut up and arranged to form karyotype diagram

Karyotype Autosomes Sex Chromosomes

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

Sex Determination female (XX) male (XY) eggs sperm Y X X x XX XY X Y Figure 12.5 Page 198

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

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

Pedigree A chart showing the genetic connections between individuals A genetic family tree Often groups of people whose heritage is well documented or who are somewhat isolated from others are used to develop pedigrees. E.g. Icelanders, Mormons, Ashkenazi Jews, Amish, Sardinians

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

Example: Pedigree of Polydactyly II III IV V female male 5,5 6,6 * 5,5 6,6 6,6 5,5 6,6 5,5 6 7 5,5 6,6 5,5 6,6 5,5 6,6 5,5 6,6 5,6 6,7 12 6,6 6,6 *Gene not expressed in this carrier.

Hemophilia

Polydactyly or Extra Digits

Linked Genes Genes found on one type of chromosome Linked genes can assort separately from on another only through crossing over The closer to genes are to each other on a chromosome, the more tightly linked they are (i.e. the more likely they are to assort together during meiosis

Markers A & C are not linked A B C D a b c d A B C D a b c d A B c d a b C D Markers A & B are linked Markers A & C are not linked

Full Linkage A B a b x Parents: A B a b AB ab F1 offspring: All AaBb meiosis, gamete formation Equal ratios of two types of gametes: A B a b 50% AB 50% ab

Incomplete Linkage AC ac A C a c x Parents: A C a c F1 offspring: All AaCc meiosis, gamete formation A a A a Unequal ratios of four types of gametes: C c c C parental genotypes recombinant genotypes

Crossover Frequency Proportional to the distance that separates genes Crossing over will disrupt linkage between A and B more often than C and D A B C D

Linkage mapping Done by using known “landmarks” or markers on chromosomes These markers are either genes or DNA fragments whose location has already been worked out By watching how these markers are inherited by those with & without the disorder, geneticists can predict the location of the gene responsible for the disorder If a gene and a marker are found together 100% of the time, they are completely linked If a gene and a marker are found together 50% of the time they are completely unlinked

Human Genetic Conditions A genetic abnormality is an uncommon or rare trait E.g. Polydactyly A genetic disorder is an inherited condition that may cause medical problems E.g. Cystic Fibrosis A syndrome is a set of symptoms that characterize a disorder E.g. Down Syndome

Human Genetic Abnormalities/Disorders Different patterns of inheritance are observed depending on the condition: Autosomal Recessive Inheritance Autosomal Dominant Inheritance X-linked inheritance

Autosomal Recessive Inheritance If parents are both heterozygous, child will have a 25% chance of being affected

Albinism

Autosomal Dominant Inheritance Trait typically appears in every generation

Huntington Disorder 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 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 Males show disorder more than females Son cannot inherit disorder from his father

Color Blindness

Hemophilia

Chromosomal Mutations Duplication Deletion Inversion Translocation

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

Duplication normal chromosome one segment repeated three repeats

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

Translocation 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

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

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

Polyploidy Individuals have three or more of each type of chromosome (3n, 4n) Common in flowering plants Found in some fish & amphibians Lethal for humans

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

nondisjunction at anaphase I chromosome alignments at metaphase I n - 1 nondisjunction at anaphase I alignments at metaphase II anaphase II Figure 12.17 Page 208

Down Syndrome 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

Aneuploidy Having one extra or one less chromosome Downs Syndrome trisomy 21 Turners Syndrome XO Klinefelters XXY Downs Syndrome

Trisomy and monosomy in sex chromosomes

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

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

Turners Syndrome Klinefelters Syndrome

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

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

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

Prenatal Diagnosis Amniocentesis Chorionic villus sampling