Chromosomes and Human Inheritance Chapter 12 Impacts, Issues: Strange Genes, Tortured Minds Exceptional creativity often accompanies neurobiological disorders such as schizophrenia, autism, chronic depression, and bipolar disorder • Examples: Lincoln, Woolf, and Picasso 12.1 Human Chromosomes In humans, two sex chromosomes are the basis of sex – human males have XY sex chromosomes, females have XX All other human chromosomes are autosomes – chromosomes that are the same in males and females Sex Determination in Humans Sex of a child is determined by the father • Eggs have an X chromosome; sperm have X or Y Sex Determination in Humans The SRY gene on the Y chromosome is the master gene for male sex determination • Triggers formation of testes, which produce the male sex hormone (testosterone) • Without testosterone, ovaries develop and produce female sex hormones (estrogens) Sexual Development in Humans diploid germ cells in male diploid germ cells in female meiosis, gamete formation in both female and male: eggs sperm X × Y X × X fertilization: X X X XX XX Y XY XY sex chromosome combinations possible in the new individual Fig. 12-2a, p. 186 Fig. 12-2bc, p. 186 At seven weeks, appearance of “uncommitted” duct system of embryo Y chromosome present At seven weeks, appearance of structures that will give rise to external genitalia Y chromosome absent testes Y chromosome present Y chromosome absent 10 weeks 10 weeks ovaries ovary penis vaginal opening uterus penis vagina birth approaching testis b c Fig. 12-2bc, p. 186 Animation: Human sex determination Karyotyping Karyotype • A micrograph of all metaphase chromosomes in a cell, arranged in pairs by size, shape, and length • Detects abnormal chromosome numbers and some structural abnormalities Construction of a karyotype • Colchicine stops dividing cells at metaphase • Chromosomes are separated, stained, photographed, and digitally rearranged Karyotyping Fig. 12-3a, p. 187 Fig. 12-3b, p. 187 Animation: Karyotype preparation 12.1 Key Concepts Autosomes and Sex Chromosomes All animals have pairs of autosomes – chromosomes that are identical in length, shape, and which genes they carry Sexually reproducing species also have a pair of sex chromosomes; the members of this pair differ between males and females 12.2 Autosomal Inheritance Patterns Many human traits can be traced to autosomal dominant or recessive alleles that are inherited in Mendelian patterns Some of those alleles cause genetic disorders Autosomal Dominant Inheritance A dominant autosomal allele is expressed in homozygotes and heterozygotes • Tends to appear in every generation • With one homozygous recessive and one heterozygous parent, children have a 50% chance of inheriting and displaying the trait • Examples: achondroplasia, Huntington’s disease Autosomal Recessive Inheritance Autosomal recessive alleles are expressed only in homozygotes; heterozygotes are carriers and do not have the trait • A child of two carriers has a 25% chance of expressing the trait • Example: galactosemia Autosomal Inheritance Fig. 12-4a, p. 188 Fig. 12-4b, p. 188 Animation: Autosomal dominant inheritance Animation: Autosomal recessive inheritance Galactosemia Neurobiological Disorders Most neurobiological disorders do not follow simple patterns of Mendelian inheritance • Depression, schizophrenia, bipolar disorders Multiple genes and environmental factors contribute to NBDs 12.3 Too Young to be Old Progeria • Genetic disorder that results in accelerated aging • Caused by spontaneous mutations in autosomes 12.2-12.3 Key Concepts Autosomal Inheritance Many genes on autosomes are expressed in Mendelian patterns of simple dominance Some dominant or recessive alleles result in genetic disorders 12.4 Examples of X-Linked Inheritance X chromosome alleles give rise to phenotypes that reflect Mendelian patterns of inheritance Mutated alleles on the X chromosome cause or contribute to over 300 genetic disorders X-Linked Inheritance Patterns More males than females have X-linked recessive genetic disorders • Males have only one X chromosome and can express a single recessive allele • A female heterozygote has two X chromosomes and may not show symptoms Males transmit an X only to their daughters, not to their sons X-Linked Recessive Inheritance Patterns Animation: X-linked inheritance Some X-Linked Recessive Disorders Hemophilia A • Bleeding caused by lack of blood-clotting protein Red-green color blindness • Inability to distinguish certain colors caused by altered photoreceptors in the eyes Duchenne muscular dystrophy • Degeneration of muscles caused by lack of the structural protein dystrophin Hemophilia A in Descendents of Queen Victoria of England Red-Green Color Blindness Fig. 12-9a, p. 191 Fig. 12-9b, p. 191 Fig. 12-9c, p. 191 Fig. 12-9d, p. 191 12.4 Key Concepts Sex-Linked Inheritance Some traits are affected by genes on the X chromosome Inheritance patterns of such traits differ in males and females 12.5 Heritable Changes in Chromosome Structure On rare occasions, a chromosome’s structure changes; such changes are usually harmful or lethal, rarely neutral or beneficial A segment of a chromosome may be duplicated, deleted, inverted, or translocated Duplication DNA sequences are repeated two or more times; may be caused by unequal crossovers in prophase I normal chromosome one segment repeated p. 192 Deletion Loss of some portion of a chromosome; usually causes serious or lethal disorders • Example: Cri-du-chat segment C deleted p. 192 Deletion: Cri-du-chat Fig. 12-10a, p. 192 Fig. 12-10b, p. 192 Inversion Part of the sequence of DNA becomes oriented in the reverse direction, with no molecular loss segments G, H, I become inverted p. 192 Translocation Typically, two broken chromosomes exchange parts (reciprocal translocation) chromosome nonhomologous chromosome reciprocal translocation p. 192 Does Chromosome Structure Evolve? Changes in chromosome structure can reduce fertility in heterozygotes; but accumulation of multiple changes in homozygotes may result in new species Certain duplications may allow one copy of a gene to mutate while the other carries out its original function Differences Among Closely Related Organisms Humans have 23 pairs of chromosomes; chimpanzees, gorillas, and orangutans have 24 • Two chromosomes fused end-to-end human chimpanzee gorilla orangutan Fig. 12-11, p. 193 Evolution of X and Y Chromosomes from Homologous Autosomes Ancestral reptiles Ancestral reptiles (autosome pair) Y X Monotremes Y X Marsupials Y X Monkeys Y X Humans Y X areas that can cross over SRY A Before 350 mya, sex was determined by temperature, not by chromosome differences. B SRY gene evolves 350 mya. Other mutations accumulate and the chromosomes of the pair diverge. areas that cannot cross over C By 320–240 mya, the two chromosomes have diverged so much that they no longer cross over in one region. The Y chromosome begins to degenerate. D Three more times, 170–130 mya, the pair stops crossing over in another region. Each time, more changes accumulate, and the Y chromosome gets shorter. Today, t he pair crosses over only at a small region near the ends. Fig. 12-12, p. 193 12.6 Heritable Changes in the Chromosome Number Occasionally, new individuals end up with the wrong chromosome number • Consequences range from minor to lethal Aneuploidy • Too many or too few copies of one chromosome Polyploidy • Three or more copies of each chromosome Nondisjunction Changes in chromosome number can be caused by nondisjunction, when a pair of chromosomes fails to separate properly during mitosis or meiosis Affects the chromosome number at fertilization • Monosomy (n-1 gamete) • Trisomy (n+1 gamete) Nondisjunction Autosomal Change and Down Syndrome Only trisomy 21 (Down syndrome) allows survival to adulthood • Characteristics include physical appearance, mental impairment, and heart defects Incidence of nondisjunction increases with maternal age Can be detected through prenatal diagnosis Trisomy 21 n+1 n+1 n−1 n−1 chromosome alignments at metaphase I NONDISJUNCTION alignments at AT ANAPHASE I metaphase II CHROMOSOME NUMBER anaphase II IN GAMETES Fig. 12-13b, p. 194 n+1 n+1 n−1 n−1 chromosome alignments at metaphase I NONDISJUNCTION alignments at AT ANAPHASE I metaphase II CHROMOSOME NUMBER anaphase II IN GAMETES Stepped Art Fig. 12-13b, p. 194 Down Syndrome and Maternal Age Fig. 12-14a, p. 195 Fig. 12-14b, p. 195 Change in Sex Chromosome Number Changes in sex chromosome number may impair learning or motor skills, or be undetected Female sex chromosome abnormalities • Turner syndrome (XO) • XXX syndrome (three or more X chromosomes) Male sex chromosome abnormalities • Klinefelter syndrome (XXY) • XYY syndrome Turner Syndrome XO (one unpaired X chromosome) • Usually caused by nondisjunction in the father • Results in females with undeveloped ovaries 12.5-12.6 Key Concepts: Changes in Chromosome Structure or Number On rare occasions, a chromosome may undergo a large-scale, permanent change in its structure, or the number of autosomes or sex chromosomes may change In humans, such changes usually result in a genetic disorder 12.7 Human Genetic Analysis Charting genetic connections with pedigrees reveals inheritance patterns for certain alleles Pedigree • A standardized chart of genetic connections • Used to determine the probability that future offspring will be affected by a genetic abnormality or disorder Studying Inheritance in Humans Genetic studies can reveal inheritance patterns or clues to past events • Example: A link between a Y chromosome and Genghis Khan? Defining Genetic Disorders and Abnormalities Genetic abnormality • A rare or uncommon version of a trait; not inherently life threatening Genetic disorder • An inherited condition that causes mild to severe medical problems, characterized by a specific set of symptoms (a syndrome) Some Human Genetic Disorders and Genetic Abnormalities Stepped Art Table 12-1, p. 196 Recurring Genetic Disorders Mutations that cause genetic disorders are rare and put their bearers at risk Such mutations survive in populations for several reasons • Reintroduction by new mutations • Recessive alleles are masked in heterozygotes • Heterozygotes may have an advantage in a specific environment A Pedigree for Huntington’s Disease A progressive degeneration of the nervous system caused by an autosomal dominant allele Constructing a Pedigree for Polydactyly Animation: Pedigree diagrams 12.8 Prospects in Human Genetics Genetic analysis can provide parents with information about their future children Genetic counseling • Starts with parental genotypes, pedigrees, and genetic testing for known disorders • Information is used to predict the probability of having a child with a genetic disorder Prenatal Diagnosis Tests done on an embryo or fetus before birth to screen for sex or genetic problems • Involves risks to mother and fetus Three types of prenatal diagnosis • Amniocentesis • Chorionic villus sampling (CVS) • Fetoscopy Amniocentesis Animation: Amniocentesis Fetoscopy Preimplantation Diagnosis Used in in-vitro fertilization • An undifferentiated cell is removed from the early embryo and examined before implantation After Preimplantation Diagnosis When a severe problem is diagnosed, some parents choose an induced abortion In some cases, surgery, prescription drugs, hormone replacement therapy, or dietary controls can minimize or eliminate symptoms of a genetic disorder • Example: PKU can be managed with dietary restrictions Genetic Screening Genetic screening (widespread, routine testing for alleles associated with genetic disorders) • • • • Provides information on reproductive risks Identifies family members with a genetic disorder Used to screen newborns for certain disorders Used to estimate the prevalence of harmful alleles in a population 12.7-12.8 Key Concepts Human Genetic Analysis Various analytical and diagnostic procedures often reveal genetic disorders What an individual, and society at large, should do with the information raises ethical questions Animation: Deletion Animation: Duplication Animation: Inversion Animation: Morgan’s reciprocal crosses Animation: Translocation Video: Strange genes, richly tortured minds