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 female diploid germ cells in male meiosis, gamete formation in both female and male: eggs sperm X × Y X × X fertilization: X X Figure 12.2 (a) Punnett-square diagram showing the sex determination pattern in humans. (b) An early human embryo appears neither male nor female. Then tiny ducts and other structures that can develop into male or female reproductive organs start forming. In an XX embryo, ovaries form in the absence of the Y chromosome and its SRY gene. In an XY embryo, the gene product triggers formation of testes, which secrete a hormone that initiates development of other male traits. (c) External reproductive organs in human embryos. X XX XX Y XY XY sex chromosome combinations possible in the new individual Fig. 12-2a, p. 186

Figure 12.2 (a) Punnett-square diagram showing the sex determination pattern in humans. (b) An early human embryo appears neither male nor female. Then tiny ducts and other structures that can develop into male or female reproductive organs start forming. In an XX embryo, ovaries form in the absence of the Y chromosome and its SRY gene. In an XY embryo, the gene product triggers formation of testes, which secrete a hormone that initiates development of other male traits. (c) External reproductive organs in human embryos. Fig. 12-2bc, p. 186

At seven weeks, appearance of “uncommitted” duct system of embryo At seven weeks, appearance of structures that will give rise to external genitalia Y chromosome present Y chromosome absent Y chromosome present Y chromosome absent testes ovaries 10 weeks 10 weeks Figure 12.2 (a) Punnett-square diagram showing the sex determination pattern in humans. (b) An early human embryo appears neither male nor female. Then tiny ducts and other structures that can develop into male or female reproductive organs start forming. In an XX embryo, ovaries form in the absence of the Y chromosome and its SRY gene. In an XY embryo, the gene product triggers formation of testes, which secrete a hormone that initiates development of other male traits. (c) External reproductive organs in human embryos. ovary penis vaginal opening uterus penis vagina testis birth approaching b c Fig. 12-2bc, p. 186

Animation: Human sex determination

Karyotyping Karyotype Construction of a 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

Figure 12.3 Karyotyping, a diagnostic tool that reveals an image of a single cell’s diploid complement of chromosomes. This human karyotype shows 22 pairs of autosomes and a pair of X chromosomes. Figure It Out: Was this cell taken from a male or female? Answer: Female Fig. 12-3a, p. 187

Figure 12.3 Karyotyping, a diagnostic tool that reveals an image of a single cell’s diploid complement of chromosomes. This human karyotype shows 22 pairs of autosomes and a pair of X chromosomes. Figure It Out: Was this cell taken from a male or female? Answer: Female 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

Figure 12.4 (a) Example of autosomal dominant inheritance. A dominant allele (red) is fully expressed in heterozygotes. Achondroplasia, an autosomal dominant disorder, affects the three men shown above. At center, Verne Troyer (Mini Me in the Mike Myers spy movies), stands two feet, eight inches tall. (b) An autosomal recessive pattern. In this example, both parents are heterozygous carriers of the recessive allele (red). Fig. 12-4a, p. 188

Figure 12.4 (a) Example of autosomal dominant inheritance. A dominant allele (red) is fully expressed in heterozygotes. Achondroplasia, an autosomal dominant disorder, affects the three men shown above. At center, Verne Troyer (Mini Me in the Mike Myers spy movies), stands two feet, eight inches tall. (b) An autosomal recessive pattern. In this example, both parents are heterozygous carriers of the recessive allele (red). 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

Figure 12.9 Left, what red–green color blindness means, using ripe red cherries on a green-leafed tree as an example. In this case, the perception of blues and yellows is normal, but the affected individual has difficulty distinguishing red from green. Right, two of many Ishihara plates, which are standardized tests for different forms of color blindness. (a) You may have one form of red–green color blindness if you see the numeral 7 instead of 29 in this circle. (b) You may have another form if you see a 3 instead of an 8. Fig. 12-9a, p. 191

Figure 12.9 Left, what red–green color blindness means, using ripe red cherries on a green-leafed tree as an example. In this case, the perception of blues and yellows is normal, but the affected individual has difficulty distinguishing red from green. Right, two of many Ishihara plates, which are standardized tests for different forms of color blindness. (a) You may have one form of red–green color blindness if you see the numeral 7 instead of 29 in this circle. (b) You may have another form if you see a 3 instead of an 8. Fig. 12-9b, p. 191

Figure 12.9 Left, what red–green color blindness means, using ripe red cherries on a green-leafed tree as an example. In this case, the perception of blues and yellows is normal, but the affected individual has difficulty distinguishing red from green. Right, two of many Ishihara plates, which are standardized tests for different forms of color blindness. (a) You may have one form of red–green color blindness if you see the numeral 7 instead of 29 in this circle. (b) You may have another form if you see a 3 instead of an 8. Fig. 12-9c, p. 191

Figure 12.9 Left, what red–green color blindness means, using ripe red cherries on a green-leafed tree as an example. In this case, the perception of blues and yellows is normal, but the affected individual has difficulty distinguishing red from green. Right, two of many Ishihara plates, which are standardized tests for different forms of color blindness. (a) You may have one form of red–green color blindness if you see the numeral 7 instead of 29 in this circle. (b) You may have another form if you see a 3 instead of an 8. 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

Figure 12.10 Cri-du-chat syndrome. (a) This infant’s ears are low relative to his eyes. (b) Same boy, four years later. The high-pitched monotone of cri-du-chat children may persist into their adulthood. Fig. 12-10a, p. 192

Figure 12.10 Cri-du-chat syndrome. (a) This infant’s ears are low relative to his eyes. (b) Same boy, four years later. The high-pitched monotone of cri-du-chat children may persist into their adulthood. 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)

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 Figure 12.11 Banding patterns of human chromosome 2 (a), compared with two chimpanzee chromosomes (b). Bands appear because different regions of the chromosomes take up stain differently. human chimpanzee gorilla orangutan Fig. 12-11, p. 193

Evolution of X and Y Chromosomes from Homologous Autosomes

areas that cannot cross over SRY Ancestral reptiles Ancestral reptiles Y X Monotremes Y X Marsupials Y X Monkeys Y X Humans Y X (autosome pair) areas that can cross over areas that cannot 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. 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. Figure 12.12 Evolution of the Y chromosome. Mya stands for million years ago. 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

chromosome alignments at metaphase I CHROMOSOME NUMBER IN GAMETES Figure 12.13 (a) A case of nondisjunction. This karyotype reveals the trisomic 21 condition of a human female. (b) One example of how nondisjunction arises. Of the two pairs of homologous chromosomes shown here, one fails to separate during anaphase I of meiosis. The chromosome number is altered in the gametes that form after meiosis. n − 1 chromosome alignments at metaphase I CHROMOSOME NUMBER IN GAMETES NONDISJUNCTION AT ANAPHASE I alignments at metaphase II anaphase II Fig. 12-13b, p. 194

chromosome alignments at metaphase I NONDISJUNCTION AT ANAPHASE I alignments at metaphase II anaphase II n + 1 n − 1 CHROMOSOME NUMBER IN GAMETES Figure 12.13 (a) A case of nondisjunction. This karyotype reveals the trisomic 21 condition of a human female. (b) One example of how nondisjunction arises. Of the two pairs of homologous chromosomes shown here, one fails to separate during anaphase I of meiosis. The chromosome number is altered in the gametes that form after meiosis. Stepped Art Fig. 12-13b, p. 194

Down Syndrome and Maternal Age

Figure 12.14 Relationship between the frequency of Down syndrome and mother’s age at childbirth. The data are from a study of 1,119 affected children. The risk of having a trisomic 21 baby rises with the mother’s age. About 80 percent of trisomic 21 individuals are born to women under thirty-five, but these women have the highest fertility rates, and they have more babies. Fig. 12-14a, p. 195

Figure 12.14 Relationship between the frequency of Down syndrome and mother’s age at childbirth. The data are from a study of 1,119 affected children. The risk of having a trisomic 21 baby rises with the mother’s age. About 80 percent of trisomic 21 individuals are born to women under thirty-five, but these women have the highest fertility rates, and they have more babies. 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