* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download PowerPoint to accompany Hole`s Human Anatomy and Physiology
Non-coding DNA wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Population genetics wikipedia , lookup
Genetic engineering wikipedia , lookup
Gene desert wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Pathogenomics wikipedia , lookup
Genomic library wikipedia , lookup
Long non-coding RNA wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Point mutation wikipedia , lookup
Polymorphism (biology) wikipedia , lookup
Human genome wikipedia , lookup
Epigenetics of diabetes Type 2 wikipedia , lookup
Public health genomics wikipedia , lookup
Hardy–Weinberg principle wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Ridge (biology) wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
History of genetic engineering wikipedia , lookup
Minimal genome wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Genome evolution wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Skewed X-inactivation wikipedia , lookup
Gene expression profiling wikipedia , lookup
Gene expression programming wikipedia , lookup
Genomic imprinting wikipedia , lookup
Neocentromere wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Y chromosome wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Designer baby wikipedia , lookup
Dominance (genetics) wikipedia , lookup
Microevolution wikipedia , lookup
Chapter 24 *Lecture Outline with Anatomy & Physiology Revealed Images *See separate Image PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Type Institution Name Here Type Course Number Here: Type Course Name Here Chapter 24 Type Professor Name Here Type Academic Rank Here Type Department Name Here 2 24.1: Introduction • Packaged into our cells are instruction manuals • The manual is the human genome • It is written in the language of the DNA molecules • DNA consists of a sequence of nucleotide building blocks A, G, C, and T • Sequences of DNA that encode particular proteins are called genes • A gene has different forms and can vary from individual to individual • Genetics is the study of the inheritance of characteristics • A genome is a complete set of genetic instructions • Genomics is the field in which the body is studied in terms of multiple, interacting genes • The exome consists of the protein-encoding genes of the genome…accounts for less than 2% or the 3.2 billion DNA bases of the human genome. • The environment influences how genes are expressed 3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Base pair DNA Gene Cell Nucleus Chromosome 4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromosome 7 Organs affected in cystic fibrosis Airways Mucus-clogged bronchi and bronchioles. Respiratory infections. (Common) DNA Transcription Liver Blocked small bile ducts impair digestion. (Rare) mRNA Pancreas Blocked ducts prevent release of digestive enzymes, impairing fat digestion. Diabetes is possible. (Common) Translation Intestines Hard stools may block intestines. (Rare) Reproductive tract Cell membrane Absence of ductus deferens. (Common) Cystic fibrosis transmembrane conductance regulator (CFTR) protein Skin Salty sweat. (Common) 5 (a) (b) 24.2: Modes of Inheritance • Genetics has the power of prediction • Knowing how genes are distributed in meiosis and the combinations in which they join at fertilization makes it possible to calculate the probability that a certain trait will appear in the offspring of two particular individuals • These patterns in which genes are transmitted in families are termed modes of inheritance 6 Chromosomes and Genes Are Paired • This normal karyotype shows 23 pairs of chromosomes: • Pairs 1-22 are autosomes (they do not determine sex) • Pair 23 are the sex chromosomes (XX female, XY male) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 2 3 6 7 8 13 14 15 19 4 9 5 11 10 16 20 17 21 Sex chromosomes (female) © SPL/Photo Researchers, Inc. 12 18 22 7 Chromosomes and Genes Are Paired • A gene consists of hundreds of nucleotide building blocks and exists in variant forms called alleles that differ in DNA sequence • An individual who has two identical alleles of a particular gene is homozygous for that gene • A person with two different alleles for a gene is heterozygous • The particular combination of gene variants (alleles) in a person’s genome constitutes the genotype • The appearance or health condition of the individual that develops as a result of the ways the genes are expressed is termed the phenotype • Wild type alleles are normal and/or most common • A mutant allele is a change from the wild type….not all cause disease 8 Dominant and Recessive Inheritance • For many genes, in heterozygotes, one allele determines the phenotype • Dominant allele masks the phenotype of the recessive allele • Recessive allele is expressed only if in a double dose (homozygous) • Autosomal conditions are carried on a non-sex chromosome • Sex-linked conditions are carried on a sex chromosome • X-linked conditions are carried on the X chromosome • Y-linked conditions are carried on the Y chromosome • A pedigree is a diagram that depicts family relationships and known genotypes and phenotypes 9 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. + = wild type allele cf = cystic fibrosis allele • Autosomal Recessive Inheritance • 3:1 Phenotype • 1:2:1 Genotype + cf + cf Carrier parents For each child conceived: + + + 25% chance unaffected noncarrier (a) cf + cf cf cf 50% chance unaffected 25% chance carrier (cf allele inherited affected from either parent) cf I cf cf cf Joe Mary cf cf 10 II (b) Punnett Square (c) Bill Sue Tina Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Autosomal Dominant Inheritance • 1:1 Phenotype • 1:1 Genotype + = wild type allele HD = Huntington disease allele + HD ++ Affected parent Unaffected parent For each Individual conceived: 50% chance unaffected 50% chance affected ++ + HD (a) I HD HD Dan Ann Pam Eric HD 11 II (b) Punnett Square (c) Different Dominance Relationships • Most genes exhibit complete dominance or recessiveness • Exceptions are incomplete dominance and codominance Plasma cholesterol (milligrams/deciliter) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1000 Homozygotes for FH 900 800 700 600 500 Heterozygotes for FH 400 • Incomplete dominance • Heterozygote has a phenotype intermediate between homozygous dominant and homozygous recessive • Familial hypercholesterolemia is an example here 300 200 General population 100 0 From Genest, Jacques, Jr., Lavoie, Marc-Andre. August 12, 1999. "Images in Clinical Medicine." New England Journal of Medicine, pp 490. ©1999, Massachusetts Medical Society. All Rights Reserved. 12 Different Dominance Relationships • Codominance • Different alleles expressed in a heterozygote are codominant • ABO blood type is an example: •Three alleles of ABO blood typing are IA, IB, I •A person with type A may have the genotype IA i or IA IA •A person with type B may have the genotype IB i or IB IB •A person with type AB must have the genotype IA IB •A person with type O blood must have the genotype ii 13 24.1 Clinical Application Genetic Counselors Communicate Modes of Inheritance 14 24.3: Factors That Affect Expression of Single Genes • Most genotypes vary somewhat from person to person, due to the effects of the environment and other genes • Penetrance, expressivity, and pleiotropy describe distinctions of genotype 15 Penetrance and Expressivity • Complete penetrance • Everyone who inherits the disease causing alleles has some symptoms • Incomplete penetrance • Some individuals do not express the phenotype even though they inherit the alleles • An example is polydactyly • Variable expression • Symptoms vary in intensity in different people • For example, two extra digits versus three extra digits in polydactyly 16 Pleiotropy • Pleiotropy • A single genetic disorder producing several symptoms • Marfan syndrome (an autosomal dominant defect) is an example • People affected produce several symptoms that vary 17 Genetic Heterogeneity • Genetic heterogeneity • The same phenotype resulting from the actions of different genes • Hereditary deafness is an example 18 24.4: Multifactorial Traits • Most if not all characteristics and disorders considered “inherited” actually reflect input from the environment as well as genes • Polygenic traits • Determined by more than one gene • Examples include height, skin color, and eye color • Blood type O without genotype ii. Due to homozygous recessive expression of another gene, therefore blood types A and B are not possible – called Bombay phenotype • Multifactorial traits • Traits molded by one or more genes plus environmental factors • Examples include height and skin color • Common diseases such as heart disease, diabetes mellitus, hypertension, and cancers are multifactorial 19 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (a) 20 (b) a: © Library of Congress; b: © Peter Morenus/University of Connecticut at Storrs Frequency Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. aabbcc Aabbcc aaBbcc aabbCc 0 1 AaBbcc AabbCc aaBbCc AAbbcc aaBBcc aabbCC AaBbCc aaBbCC AAbbCc AabbCC AABbcc aaBBCc AaBBcc aaBBCC AAbbCC AABBcc AaBbCC AaBBCC AaBBCc AABbCC AABbCc AABBCc AABBCC 2 3 4 Number of dominant alleles 5 6 21 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. AaBb AB Ab aB ab AABB AABb AaBB AaBb AB Number of Phenotype dominant frequency alleles Ab AABb AAbb AaBb Aabb 1/16 0 4/16 1 6/16 2 4/16 3 1/16 4 Light blue AaBb aB AaBB AaBb aaBB aaBb Deep blue or green Light brown ab AaBb Aabb aaBb aabb Medium brown Dark brown/black 22 24.5: Matters of Sex • Human somatic (nonsex) cells include an X and a Y chromosome in males and two X chromosomes in females • All eggs carry a single X chromosome • Sperm carry either an X or Y chromosome • Sex is determined at conception: a Y-bearing sperm fertilizing an egg conceives a male, and an X-bearing sperm conceives a female 23 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. X Y X-bearing sperm Y-bearing sperm + + X X Egg Egg XX female XY male 24 Sex Determination Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Maleness derives from a Y chromosome gene called SRY • The SRY gene encodes a type of protein called a transcription factor • The SRY activates transcription of genes that direct development of male structures in the embryo, while suppressing formation of female structures SRY gene X chromosome Y chromosome © Biophoto Associates/Photo Researchers, Inc. 25 Genes of the Sex Chromosomes • X chromosome • Has over 1,500 genes • Most genes on the X chromosome do not have corresponding alleles on the Y chromosome • Y chromosome • Has only 231 protein-encoding genes • Some genes are unique only to the Y chromosome • The human male is hemizygous for X-linked traits because he only has one copy of each X chromosome gene • Some recessive X-linked traits expressed in males include: • Red-green colorblindness • Hemophilia 26 Hemophilia • Passed from mother (heterozygote) to son • Each son has a 50% chance of receiving the recessive allele from the mother • Each son with one recessive allele will have the disease • Each son has no allele on the Y chromosome to mask the recessive allele • Each daughter has a 50% chance of receiving the recessive allele from the mother • Each daughter with one recessive allele will be a carrier • Each daughter with one recessive allele does not develop the disease because she has another X chromosome with a dominant allele 27 Gender Effects on Phenotype • Sex-limited trait • Affects a structure or function of the body that is present in only males or only females • Examples are beards or growth of breasts • Sex-influenced inheritance • An allele is dominant in one sex and recessive in the other • Baldness is an example • Heterozygous males are bald but heterozygous females are not • Genomic imprinting • The expression of a disorder differs depending upon which parent transmits the disease-causing gene or chromosome 28 24.6: Chromosome Disorders • Deviations from the normal chromosome number of 46 produce syndromes because of the excess or deficit of genes • Chromosome number abnormalities may involve single chromosomes or entire sets of chromosomes • Euploid is a normal chromosome number 29 Polyploidy • Polyploidy • The most drastic upset in chromosome number • This is an entire extra set of chromosomes • Results from formation of a diploid, rather than a normal haploid, gamete • Most embryos or fetuses die, but occasionally an infant survives a few days with many abnormalities 30 Aneuploidy • Aneuploidy • Cells missing a chromosome or having an extra chromosome • Results from meiotic error called nondisjunction • Here a chromosome pair fails to separate, either at the first or at the second meiotic division, producing a sperm or egg that has two copies of a particular chromosome or none, rather than the normal one copy • When a gamete fuses with its mate at fertilization, the resulting zygote has either 47 or 45 chromosomes, instead of 46 • Trisomy is the condition of having an extra chromosome • Monosomy is the condition of missing a chromosome 31 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. A A a a A A a a Primary spermatocyte First division nondisjunction A A a Meiosis I a Secondary spermatocyte A a A a Second division nondisjunction Meiosis II Sperm A a A A a A a a Fertilization of euploid egg Zygotes Monosomic (a) Monosomic Trisomic Trisomic Euploid (b) Euploid Monosomic Trisomic 32 33 24.2 Clinical Application Down Syndrome 34 Prenatal Tests Detect Chromosome Abnormalities • Several types of tests performed on pregnant women can identify anatomical or physiological features of fetuses that can indicate a chromosomal problem or detect the abnormal chromosomes 35 Prenatal Tests Detect Chromosome Abnormalities Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chorionic villi Uterus Placenta Amniotic membrane Fetus Catheter Rare fetal cells Cervix Fetus 15–16 weeks Vagina (b) Amniocentesis Syringe (a) Chorionic villus sampling (c) Fetal cell sorting 36 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 37 © Bernard Bennot/SPL/Photo Researchers, Inc. 24.7: Genetics and Personalized Medicine • Even though it is possible for people to have their genomes sequenced, single-gene tests or symptoms may be more useful than knowing the sequence of the entire genome • Gene expression is identifying which genes are active and inactive in particular cell types, under particular conditions • Gene expression monitors the proteins that a cell produces • Considering patterns of gene expression my be more helpful than knowing a sequence of DNA bases • Changes in gene expression accompany all diseases • Gene expression data can be used to suggest new ways to treat diseases and to track responses to treatments 38 Important Points in Chapter 24: Outcomes to be Assessed 24.1: Introduction Distinguish among gene, chromosome, and genome. Explain how the human genome is an economical storehouse of information. Explain how the environment influences how genes are expressed. 24.2: Modes of Inheritance Describe a karyotype, and explain what it represents. Explain the basis of multiple alleles of a gene. 39 Important Points in Chapter 24: Outcomes to be Assessed Distinguish between heterozygous and homozygous; genotype and phenotype; dominant and recessive. Distinguish between autosomal recessive and autosomal dominant inheritance. 24.3: Factors That Affect Expression of Single Genes Explain how and why the same genotype can have different phenotypes among individuals. 24.4: Multifactorial Traits Describe and give examples of how genes and the environment determine traits. 40 Important Points in Chapter 24: Outcomes to be Assessed 24.5: Matters of Sex Describe how and when sex is determined. Explain how X-linked inheritance differs from inheritance of autosomal traits. Discuss factors that affect how phenotypes may differ between the sexes. 24.6: Chromosome Disorders Describe three ways that chromosomes can be abnormal. Explain how prenatal tests provide information about chromosomes. 41 Important Points in Chapter 24: Outcomes to be Assessed 24.7: Genetics and Personalized Medicine Contrast the value of whole genome sequencing with that of single gene tests. Explain how understanding gene expression patterns can improve and personalize health care. 42 Quiz 24 Complete Quiz 24 now! Congratulations! You have completed Hole’s Anatomy & Physiology, 13e. 43