29 Heredity

Study of mechanism of heredity Genetics Study of mechanism of heredity Basic principles proposed by Mendel in mid-1800s © 2013 Pearson Education, Inc.

The Vocabulary of Genetics Diploid number (46) of chromosomes in all cells except gametes 23 pairs of homologous chromosomes 1 pair-sex chromosomes Determine genetic sex (XX = female, XY = male) 22 pairs–autosomes Guide expression of most other traits © 2013 Pearson Education, Inc.

The Vocabulary of Genetics Karyotype diploid chromosomal complement displayed in homologous pairs Genom -genetic (DNA) makeup; two sets of genetic instructions (maternal and paternal) © 2013 Pearson Education, Inc.

Figure 29.1 Preparing a karyotype. The slide is viewed with a microscope, and the chromosomes are photographed. 2 The photograph is entered into a computer, and the chromosomes are electronically rearranged into homologous pairs according to size and structure. 3 The resulting display is the karyotype, which is examined for chromosome number and structure. © 2013 Pearson Education, Inc.

Gene Pairs Alleles Matched genes at same locus (location) on homologous chromosomes Homozygous–alleles same for single trait Heterozygous–alleles different for single trait © 2013 Pearson Education, Inc.

Gene Pairs Dominant-one allele masks (suppresses) its recessive partner Dominant denoted by capital letter; recessive by same letter in lower case Dominant expressed if one or both alleles dominant Recessive expressed only if both alleles recessive © 2013 Pearson Education, Inc.

Genotype and Phenotype Genotype–genetic makeup Phenotype–expression of genotype © 2013 Pearson Education, Inc.

Sexual Sources of Genetic Variation Each person unique due to three events Independent assortment of chromosomes Crossover of homologues Random fertilization of eggs by sperm © 2013 Pearson Education, Inc.

Chromosome Segregation and Independent Assortment During gametogenesis, maternal and paternal chromosomes randomly distributed to daughter cells Alleles for each trait segregated during meiosis I  Gamete receives only one allele of the four alleles (2 maternal / 2 paternal) for each trait Alleles on different pairs of homologous chromosomes distributed independently © 2013 Pearson Education, Inc.

Segregation and Independent Assortment Independent assortment  incredible variety Number of gamete types = 2n, where n = number of homologous pairs In testes, 2n = 2223 = 8.5 million © 2013 Pearson Education, Inc.

Figure 29.2 Gamete variability resulting from independent assortment. Maternal chromosomes Paternal chromosomes © 2013 Pearson Education, Inc.

Crossover and Genetic Recombination Genes on same chromosome linked Normally pass to daughter cells as unit Homologous chromosomes can break, even between linked genes  precisely exchange gene segments (crossover or chiasma)  Recombinant chromosomes Chromosomes have mixed contributions from each parent  Tremendous variability © 2013 Pearson Education, Inc.

Figure 29.3 Crossover and genetic recombination. (1 of 4) Hair color genes Eye color genes Homologous chromosomes synapse during prophase of meiosis I. Each chromosome consists of two sister chromatids. H Allele for brown hair E Allele for brown eyes h Allele for blond hair e Allele for blue eyes Paternal chromosome Homologous pair Maternal chromosome © 2013 Pearson Education, Inc.

Figure 29.3 Crossover and genetic recombination. (2 of 4) Chiasma One chromatid segment exchanges positions with a homologous chromatid segment—in other words, crossing over occurs, forming a chiasma. H Allele for brown hair E Allele for brown eyes h Allele for blond hair e Allele for blue eyes Paternal chromosome Homologous pair Maternal chromosome © 2013 Pearson Education, Inc.

Figure 29.3 Crossover and genetic recombination. (3 of 4) The chromatids forming the chiasma break, and the broken-off ends join their corresponding homologues. H Allele for brown hair E Allele for brown eyes h Allele for blond hair e Allele for blue eyes Paternal chromosome Homologous pair Maternal chromosome © 2013 Pearson Education, Inc.

Figure 29.3 Crossover and genetic recombination. (4 of 4) Gamete 1 Gamete 2 Gamete 3 Gamete 4 At the conclusion of meiosis, each haploid gamete has one of the four chromosomes shown. Two of the chromosomes are recombinant (they carry new combinations of genes). H Allele for brown hair E Allele for brown eyes h Allele for blond hair e Allele for blue eyes Paternal chromosome Homologous pair Maternal chromosome © 2013 Pearson Education, Inc.

Single egg fertilized by single sperm in random manner Random Fertilization Single egg fertilized by single sperm in random manner Independent assortment and random fertilization ~ 72 trillion (8.5 million  8.5 million) zygote possibilities Random fertilization increases number of possibilities exponentially © 2013 Pearson Education, Inc.

Few phenotypes traced to single gene Types of Inheritance Few phenotypes traced to single gene Most traits determined by multiple alleles or by interaction of several gene pairs © 2013 Pearson Education, Inc.

Dominant-Recessive Inheritance Reflects interaction of dominant and recessive alleles Punnett square Predicts possible gene combinations resulting from mating of parents of known genotypes Only probability of particular genotype (phenotype) © 2013 Pearson Education, Inc.

Dominant-Recessive Inheritance Example Probability of genotypes from mating two heterozygous parents Dominant allele—capital letter; recessive allele—lowercase letter T = tongue roller and t = cannot roll tongue TT and tt are homozygous; Tt is heterozygous © 2013 Pearson Education, Inc.

Dominant-Recessive Inheritance Offspring: 25% TT; 50% Tt; 25% tt Larger number of offspring  greater likelihood ratios conform to predicted values Probability of two children with same genotype Multiply probabilities of separate events E.g., probability of two children who cannot roll tongue = 1/4 * 1/4 = 1/16 © 2013 Pearson Education, Inc.

Tt female Tt male Heterozygous female forms two types of gametes Figure 29.4 Genotype and phenotype probabilities resulting from a mating of two heterozygous parents. Tt female Tt male Heterozygous female forms two types of gametes Heterozygous male forms two types of gametes 1/2 T T 1/2 TT 1/2 t t 1/2 1/4 tT Tt 1/4 1/4 tt 1/4 Possible combinations in offspring © 2013 Pearson Education, Inc.

Dominant traits (for example, widow's peaks, freckles, dimples) Dominant disorders uncommon; many lethal  death before reproductive age Huntington's disease caused by delayed-action gene Activated ~ age 40 Dominant gene possibly passed to offspring–50% chance © 2013 Pearson Education, Inc.

Recessive Inheritance Some recessive genes more desirable condition E.g., normal vision-recessive; astigmatism - dominant Most genetic disorders inherited as simple recessive traits Albinism, cystic fibrosis, and Tay-Sachs disease Heterozygotes–carriers; do not express trait but can pass to offspring © 2013 Pearson Education, Inc.

Table 29.1 Traits Determined by Simple Dominant-Recessive Inheritance. © 2013 Pearson Education, Inc.

Heterozygous individuals have intermediate phenotype Incomplete Dominance Heterozygous individuals have intermediate phenotype Rare in humans; example-Sickling gene SS = normal Hb made Ss = sickle-cell trait; both aberrant and normal Hb made; can suffer sickle-cell crisis under prolonged reduction in blood O2 ss = sickle-cell anemia; only aberrant Hb made; more susceptible to sickle-cell crisis © 2013 Pearson Education, Inc.

… Val His Leu Thr Pro Val Glu 1 2 3 4 5 6 7 146 Figure 17.8b Sickle-cell anemia. … Val His Leu Thr Pro Val Glu 1 2 3 4 5 6 7 146 Sickled erythrocyte results from a single amino acid change in the beta chain of hemoglobin. © 2013 Pearson Education, Inc.

Multiple-Allele Inheritance Genes that exhibit more than two allele forms E.g., ABO blood grouping Three alleles (IA, IB, i) determine ABO blood type in humans Each person has only two IA and IB-codominant (both expressed if present) i - recessive © 2013 Pearson Education, Inc.

Table 29.2 ABO Blood Groups. © 2013 Pearson Education, Inc.

Sex-Linked Inheritance Inherited traits determined by genes on sex chromosomes X chromosomes bear over 2500 genes (many for brain function); Y chromosomes carry about 78 genes Few regions can participate in crossover © 2013 Pearson Education, Inc.

Sex-Linked Inheritance X-linked genes - found only on X chromosome X-linked recessive alleles always expressed in males Never masked or damped in males (no Y counterpart) Most X-linked conditions expressed in males Passed from mothers to sons (e.g., hemophilia or red-green color blindness); never father to sons Passed from mothers to daughters, but females require two alleles to express © 2013 Pearson Education, Inc.

Traits reflecting actions of several gene pairs at different locations Polygene Inheritance Traits reflecting actions of several gene pairs at different locations Results in continuous phenotypic variation between two extremes Examples: skin color, eye color, height, intelligence, metabolic rate © 2013 Pearson Education, Inc.

Polygene Inheritance of Skin Color Alleles for dark skin (ABC) incompletely dominant over those for light skin (abc) First-generation offspring of AABBCC X aabbcc cross  all heterozygous (intermediate pigmentation) Second-generation offspring have wide variation in possible pigmentations  bell-shaped curve © 2013 Pearson Education, Inc.

Proportion of second-generation population Figure 29.6 Simplifiedmodel for polygene inheritance of skin color based on three gene pairs. Parents 3 aabbcc (very light) AABBCC (very dark) First-generation offspring 3 AaBbCc AaBbCc 20/64 15/64 Proportion of second-generation population 6/64 1/64 1/64 6/64 15/64 20/64 15/64 6/64 1/64 © 2013 Pearson Education, Inc.

Environmental Factors in Gene Expression Maternal factors (e.g., drugs, pathogens) alter normal gene expression during embryonic development E.g., thalidomide Embryos developed phenotypes not directed by their genes Phenocopies-environmentally produced phenotypes; mimic conditions caused by genetic mutations © 2013 Pearson Education, Inc.

Environmental Factors in Gene Expression Environmental factors influence gene expression after birth Poor nutrition affects brain growth, body development, and height Childhood hormonal deficits can lead to abnormal skeletal growth and proportions © 2013 Pearson Education, Inc.

Nontraditional Inheritance Genetic outcomes influenced by Small RNAs Epigenetic marks (chemical groups attached to DNA or histone proteins) Extranuclear inheritance (mitochondrial DNA) © 2013 Pearson Education, Inc.

Nontraditional Inheritance: Regulation of Gene Expression Three levels of controls in human genome First layer - protein-coding genes Less than 2% of DNA Second layer–small RNAs In non-protein-coding DNA Third layer–epigenetic marks Stored in proteins and chemical groups that bind to DNA; and in way chromatin packaged © 2013 Pearson Education, Inc.

MicroRNAs (miRNAs) and short interfering RNAs (siRNAs) Small RNAs MicroRNAs (miRNAs) and short interfering RNAs (siRNAs) Act directly on DNA, other RNAs, or proteins Inactivate transposons, genes that tend to replicate themselves and disable or hyperactivate other genes Control timing of apoptosis during development Prevent translation of another gene Mutations linked to prostate and lung cancers, and schizophrenia © 2013 Pearson Education, Inc.

Nucleotide sequences for small RNAs now determined Extensive gene therapy research to develop RNA-interfering drugs for diseases such as Age-related macular degeneration, Parkinson's disease, cancer, and other disorders © 2013 Pearson Education, Inc.

May predispose cell to cancerous changes or devastating illness Epigenetic Marks Information stored in proteins and chemical groups (e.g., methyl and acetyl groups) bound to DNA; and in way chromatin packaged in cell Determine whether DNA available for transcription (acetylation) or silenced (methylation) May predispose cell to cancerous changes or devastating illness © 2013 Pearson Education, Inc.

Allows embryo to express only mother's or father's gene Epigenetic Marks Genomic imprinting Tags certain genes with methyl group during gametogenesis as maternal or paternal; essential for normal development Allows embryo to express only mother's or father's gene Each new generation erases imprinting when new gametes produced © 2013 Pearson Education, Inc.

Mutations of imprinted genes may  pathology Epigenetic Marks Mutations of imprinted genes may  pathology Same allele can have different effects depending on which parent it comes from For example, deletions in chromosome 15 result in disorders with different symptoms Prader-Willi syndrome if inherited from father Angelman syndrome if inherited from mother © 2013 Pearson Education, Inc.

Extranuclear (Mitochondrial) Inheritance Some genes (37) in mitochondrial DNA (mtDNA) Transmitted by mother in cytoplasm of egg Errors in mtDNA linked to rare disorders Muscle disorders and neurological problems, possibly Alzheimer's and Parkinson's diseases © 2013 Pearson Education, Inc.

Genetic Screening, Counseling, and Therapy Newborn infants routinely screened for number of genetic disorders Congenital hip dysplasia, imperforate anus, PKU, and other metabolic disorders Other examples Screening adult children of parents with Huntington's disease; testing fetus of 35 yo woman for trisomy-21 (Down syndrome) © 2013 Pearson Education, Inc.

Two ways to identify gene carriers Pedigrees Carrier Recognition Two ways to identify gene carriers Pedigrees and blood tests Pedigrees Trace genetic trait through several generations; helps predict future © 2013 Pearson Education, Inc.

Carrier Recognition Blood tests and DNA probes can detect presence of unexpressed recessive genes E.g., Tay-Sachs and cystic fibrosis genes © 2013 Pearson Education, Inc.

Chorionic villus sampling (CVS) Fetal Testing Used when known risk of genetic disorder; both invasive; both carry risk Amniocentesis Amniotic fluid withdrawn after 14th week; fluid and cells examined for genetic abnormalities Testing takes several weeks Chorionic villus sampling (CVS) Chorionic villi sampled at 8-10 weeks; karyotyped for genetic abnormalities; testing ~ immediate © 2013 Pearson Education, Inc.

Figure 29.7 Fetal testing—amniocentesis and chorionic villus sampling. Chorionic villus sampling (CVS) Amniotic fluid withdrawn A sample of amniotic fluid can be taken starting at the 14th to 16th week of pregnancy. 1 A sample of chorionic villus tissue can be taken as early as the 8th to 10th week of pregnancy. 1 Fetus Placenta Fetus Centrifugation Suction tube inserted through cervix Uterus Cervix Placenta Chorionic villi Fluid Biochemical tests (tests for genetic disorders) can be performed immediately on the amniotic fluid or later on the cultured cells. 2 Fetal cells Fetal cells Biochemical tests Karyotyping and biochemical tests can be performed on the fetal cells immediately, providing results within a day or so. 2 Fetal cells must be cultured for several weeks to obtain sufficient numbers for karyotyping (testing for chromosomal disorders). 3 Several weeks Several hours Karyotyping of chromosomes of cultured cells © 2013 Pearson Education, Inc.

Amniocentesis Amnioti fluid withdrawn A sample of amniotic 1 Figure 29.7a Fetal testing—amniocentesis and chorionic villus sampling. Slide 1 Amniocentesis Amnioti fluid withdrawn A sample of amniotic fluid can be taken starting at the 14th to 16th week of pregnancy. 1 Fetus Placenta Centrifugation Uterus Cervix Fluid Biochemical tests (tests for genetic disorders) can be performed immediately on the amniotic fluid or later on the cultured cells. 2 Fetal cells Biochemical tests Fetal cells must be cultured for several weeks to obtain sufficient numbers for karyotyping (testing for chromosomal disorders). 3 Several weeks Karyotyping of chromosomes of cultured cells © 2013 Pearson Education, Inc.

Amniocentesis Amnioti fluid withdrawn A sample of amniotic 1 Figure 29.7a Fetal testing—amniocentesis and chorionic villus sampling. Slide 2 Amniocentesis Amnioti fluid withdrawn A sample of amniotic fluid can be taken starting at the 14th to 16th week of pregnancy. 1 Fetus Placenta Centrifugation Uterus Cervix Fluid Fetal cells © 2013 Pearson Education, Inc.

Amniocentesis Amnioti fluid withdrawn A sample of amniotic 1 Figure 29.7a Fetal testing—amniocentesis and chorionic villus sampling. Slide 3 Amniocentesis Amnioti fluid withdrawn A sample of amniotic fluid can be taken starting at the 14th to 16th week of pregnancy. 1 Fetus Placenta Centrifugation Uterus Cervix Fluid Biochemical tests (tests for genetic disorders) can be performed immediately on the amniotic fluid or later on the cultured cells. 2 Fetal cells Biochemical tests © 2013 Pearson Education, Inc.

Amniocentesis Amnioti fluid withdrawn A sample of amniotic 1 Figure 29.7a Fetal testing—amniocentesis and chorionic villus sampling. Slide 4 Amniocentesis Amnioti fluid withdrawn A sample of amniotic fluid can be taken starting at the 14th to 16th week of pregnancy. 1 Fetus Placenta Centrifugation Uterus Cervix Fluid Biochemical tests (tests for genetic disorders) can be performed immediately on the amniotic fluid or later on the cultured cells. 2 Fetal cells Biochemical tests Fetal cells must be cultured for several weeks to obtain sufficient numbers for karyotyping (testing for chromosomal disorders). 3 Several weeks Karyotyping of chromosomes of cultured cells © 2013 Pearson Education, Inc.

Chorionic villus sampling (CVS) Figure 29.7b Fetal testing—amniocentesis and chorionic villus sampling. Slide 1 Chorionic villus sampling (CVS) Fetus A sample ofchorionic villus tissue can be taken as early as the 8th to 10th week of pregnancy. 1 Suction tube inserted through cervix Placenta Chorionic villi Fetal cells Biochemical tests Karyotyping and biochemical tests can be performed on the fetal cells immediately, providing results within a day or so. 2 Several hours Karyotyping of chromosomes of cultured cells © 2013 Pearson Education, Inc.

Chorionic villus sampling (CVS) Figure 29.7b Fetal testing—amniocentesis and chorionic villus sampling. Slide 2 Chorionic villus sampling (CVS) Fetus A sample ofchorionic villus tissue can be taken as early as the 8th to 10th week of pregnancy. 1 Suction tube inserted through cervix Placenta Chorionic villi Fetal cells © 2013 Pearson Education, Inc.

Chorionic villus sampling (CVS) Figure 29.7b Fetal testing—amniocentesis and chorionic villus sampling. Slide 3 Chorionic villus sampling (CVS) Fetus A sample ofchorionic villus tissue can be taken as early as the 8th to 10th week of pregnancy. 1 Suction tube inserted through cervix Placenta Chorionic villi Fetal cells Biochemical tests Karyotyping and biochemical tests can be performed on the fetal cells immediately, providing results within a day or so. 2 Several hours Karyotyping of chromosomes of cultured cells © 2013 Pearson Education, Inc.

Gene therapy may alleviate or cure disorders Human Gene Therapy Gene therapy may alleviate or cure disorders Genetic engineering has potential to replace defective gene, including Defective cells infected with genetically engineered virus containing functional gene Inject "corrected" gene directly into cells Prohibitively expensive; ethical, religious, societal questions © 2013 Pearson Education, Inc.