Cecie Starr Christine Evers Lisa Starr www.cengage.com/chemistry/starr Chapter 14 Human Inheritance (Sections 14.5 - 14.7) Albia Dugger • Miami Dade College 14.5 Heritable Changes in Chromosome Structure • Major changes in chromosome structure include duplications, deletions, inversions, and translocations • Major changes in chromosome structure have been evolutionarily important • More frequently, such changes tend to result in genetic disorders Duplication • Duplications occur during prophase I of meiosis, when crossing over occurs unequally between homologous chromosomes • duplication • Repeated section of a chromosome Deletion • In mammals, deletions usually cause serious disorders and are often lethal • deletion • Loss of part of a chromosome Inversion • Inversion may not affect a carrier’s health if it doesn’t disrupt a gene, but it may affect fertility • inversion • Structural rearrangement of a chromosome in which a part becomes oriented in the reverse direction, with no molecular loss Duplication and Deletion A With a duplication, a section of a chromosome gets repeated. B With a deletion, a section of a chromosome gets lost. Fig. 14.9ab, p. 210 Inversion C With an inversion, a section of a chromosome gets flipped so it runs in the opposite orientation. Fig. 14.9c, p. 210 Translocation • If a chromosome breaks, the broken part may attach to a different chromosome, or to a different part of the same one • Most translocations are reciprocal, or balanced, which means two chromosomes exchange broken parts • translocation • Structural change of a chromosome in which a broken piece gets reattached in the wrong location Reciprocal Translocation • Many reciprocal translocations have no adverse effects on health, but can affect fertility Reciprocal Translocation D With a translocation, a broken piece of a chromosome gets reattached in the wrong place. This example shows a reciprocal translocation, in which two chromosomes exchange chunks. Fig. 14.9d, p. 210 Some Disorders with Changes in Chromosome Structure • Huntington’s disease: expansion mutations (duplications) • Degeneration of the nervous system • Cri-du-chat syndrome (deletion) • Mental impairment; abnormal larynx • Burkitt’s lymphoma (translocation) • An aggressive cancer of the immune system Chromosome Changes in Evolution • Most major alterations are harmful or lethal in humans • Even so, many major structural changes have accumulated in chromosomes of all species over evolutionary time • Speciation can and does occur by large-scale changes in chromosomes Evolution of the Y Chromosome • X and Y chromosomes were once homologous autosomes in reptilelike ancestors of mammals • About 350 mya, a gene on one chromosome mutated – interfering with crossing over during meiosis – and mutations began to accumulate separately in the two chromosomes • Today, the SRY gene (Y chromosome) determines male sex Evolution of the Y Chromosome Evolution of the Y Chromosome (autosome pair) area that cannot cross over SRY Ancestral reptiles >350 mya A Before 350 mya, sex was determined by temperature, not by chromosome differences. Ancestral reptiles 350 mya B The SRY gene begins to evolve 350 mya. The DNA sequences of the chromosomes diverge as other mutations accumulate. Monotremes 320–240 mya C By 320–240 mya, the DNA sequences of the chromosomes are so different that the pair can no longer cross over in one region. The Y chromosome begins to get shorter. Marsupials 170–130 mya Monkeys 130–80 mya Humans 50–30 mya D Three more times, the pair stops crossing over in yet another region. Each time, the DNA sequences of the chromosomes diverge, and the Y chromosome shortens. Today, the pair crosses over only at a small region near the ends. Fig. 14.10, p. 211 Human Evolution • One human chromosome matches two in chimpanzees and other great apes • During human evolution, two chromosomes fused end to end and formed our chromosome 2 Human Evolution telomere sequence human chimpanzee Fig. 14.11, p. 211 ANIMATION: Deletion To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE ANIMATION: Duplication To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE ANIMATION: Inversion To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE Animation: Translocation To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE 14.6 Heritable Changes in the Chromosome Number • Occasionally, abnormal events occur before or during meiosis, and new individuals end up with the wrong chromosome number • Consequences range from minor to lethal changes in form and function Nondisjunction • Changes in chromosome number are usually caused by nondisjunction • Nondisjunction affects chromosome number at fertilization and causes genetic disorders among resulting offspring • nondisjunction • Failure of sister chromatids or homologous chromosomes to separate during nuclear division Nondisjunction Nondisjunction Metaphase I Anaphase I Telophase I Metaphase II Anaphase II Telophase II Fig. 14.12, p. 212 Nondisjunction Metaphase I Anaphase I Telophase I Metaphase II Anaphase II Telophase II Stepped Art Fig. 14.12, p. 212 Aneuploidy • In aneuploidy, an individual’s cells have too many or too few copies of a chromosome (result of nondisjunction) • Most cases of autosomal aneuploidy are lethal in embryos • aneuploidy • A chromosome abnormality in which an individual’s cells carry too many or too few copies of a particular chromosome Types of Aneuploidy • Trisomy: • A normal gamete (n) fuses with an n+1 gamete • New individual is trisomic (2n+1), having three of one type of chromosome and two of every other type • Monosomy: • An n-1 gamete fuses with a normal (n) gamete • New individual is monosomic (2n-1) Polyploidy • Polyploid individuals have three or more of each type of chromosome • Polyploidy is lethal in humans, but many flowering plants, and some insects, fishes, and other animals, are polyploid • polyploid • Having three or more of each type of chromosome characteristic of the species Disorders with Changes in Chromosome Number Disorder Main Symptoms Down syndrome Mental impairment; heart defects Turner syndrome (XO) Sterility; abnormal ovaries and sexual traits Klinefelter syndrome Sterility; mild mental impairment XXX syndrome Minimal abnormalities XYY condition Mild mental impairment or no effect Autosomal Change and Down Syndrome • The most common aneuploidy, trisomy 21, causes Down syndrome • Characteristics include upward-slanting eyes, slightly flattened facial features, and other symptoms • Trisomic 21 individuals tend to have moderate to severe mental impairment and heart problems Down Syndrome Down Syndrome Fig. 14.13a, p. 213 Down Syndrome Fig. 14.13b, p. 213 Change in Sex Chromosome Number • A change in the number of sex chromosomes usually results in some degree of impairment in learning and motor skills • In individual with trisomy (XXY, XXX, and XYY) these problems can be subtle and the cause may never be diagnosed Female Sex Chromosome Abnormalities • Individuals with Turner syndrome have an X chromosome and no corresponding X or Y chromosome (XO) • XO individuals are well proportioned but short; their ovaries do not develop properly, so they do not make enough sex hormones to become sexually mature • In XXX syndrome, having extra X chromosomes usually does not result in physical or medical problems Male Sex Chromosome Abnormalities • Males with Klinefelter syndrome (XXY ) tend to be overweight, tall, and within normal range of intelligence • They make more estrogen and less testosterone than normal males, which has feminizing effects • XYY males tend to be taller than average and have mild mental impairment, but are otherwise normal Key Concepts • Changes in Chromosome Structure and Number • 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 Animation: Amniocentesis To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE ABC Video: Genetic Testing: Screening Embryos for Disease 14.7 Genetic Screening • Prospective parents can estimate probability that a child will inherit a genetic disorder with genetic screening, in which pedigrees and genotype are analyzed by a genetic counselor • Some disorders can be detected early enough to start countermeasures before symptoms develop Newborn Screening for PKU • Most US hospitals now screen newborns for mutations in the gene for phenylalanine hydroxylase, a defect that can cause phenylalanine to accumulate to high levels • The resulting imbalance inhibits protein synthesis in the brain, which results in severe neurological symptoms characteristic of phenylketonuria (PKU) Prenatal Diagnosis • Prenatal genetic testing of an embryo or fetus can reveal genetic abnormalities or disorders before birth • Obstetric sonography • Fetoscopy • Amniocentesis • Chorionic villus sampling (CVS) • An invasive procedure often carries a risk to the fetus Imaging a Fetus in the Uterus • Obstetric sonography (ultrasound) forms images of the fetus’s developing limbs and internal organs • Fetoscopy yields higher-resolution images Imaging a Fetus in the Uterus A An ultrasound image. Fig. 14.14a, p. 214 Imaging a Fetus in the Uterus B A fetoscopy image. Fig. 14.14b, p. 214 Tests for Genetic Disorders • With amniocentesis, fetal cells shed into the fluid inside the amniotic sac are tested for genetic disorders • Chorionic villus sampling tests cells of the chorion, which is part of the placenta Tests for Genetic Disorders amniotic sac placenta Fig. 14.15, p. 215 Preimplantation Diagnosis • Clump of cells formed by three mitotic divisions after in vitro fertilization • One cell can be removed for genetic analysis to determine whether the embryo carries any genetic defects Key Concepts • Genetic Testing • Genetic testing provides information about the risk of passing a harmful allele to one’s offspring • After conception, various methods of prenatal testing can reveal a genetic abnormality or disorder in a fetus or embryo Shades of Skin (revisited) • People of Chinese descent carry an allele of the DCT gene which results in conversion of tyrosine to melanin • Distribution of SLC24A5 and DCT genes suggests that (1) an African population was ancestral to both Chinese and Europeans, and (2) Chinese and European populations separated before their pigmentation genes mutated and their skin color changed