chapter 24 *lecture outline with anatomy & physiology revealed images copyright © the...
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Chapter 24*Lecture Outline
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Anatomy & Physiology Revealed Images
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Chapter 24
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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
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DNA
Base pair
Cell
Gene
Nucleus
Chromosome
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Chromosome 7
(a)
Organs affected in cystic fibrosis
(b)
Transcription
Translation
Cellmembrane
DNA
mRNA
Cystic fibrosistransmembraneconductanceregulator (CFTR)protein
AirwaysMucus-clogged bronchiand bronchioles.Respiratory infections.(Common)
LiverBlocked small bile ductsimpair digestion. (Rare)
PancreasBlocked ducts preventrelease of digestiveenzymes, impairing fat digestion. Diabetesis possible. (Common)
IntestinesHard stools may blockintestines. (Rare)
Reproductive tractAbsence of ductus deferens.(Common)
SkinSalty sweat. (Common)
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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
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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)
1 2 3 4 5
6 7 8 109 12
13 14 15 16 17 18
19 20 21 22
Sex chromosomes(female)
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• 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
Chromosomes and Genes Are Paired
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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
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cf
cf cf cf cf
cf
Punnett Square
Carrier parents
+ + + cf +cf cf cf
(a)
(b) (c)
For each child conceived:
I
II
MaryJoe
Bill Sue Tina
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+ = wild type allelecf = cystic fibrosis allele
+ cf + cf
25% chanceunaffectednoncarrier
50% chance unaffected carrier (cf allele inherited
from either parent)
25% chanceaffected
• Autosomal Recessive Inheritance
• 3:1 Phenotype• 1:2:1 Genotype
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(a)
(b) (c)
I
II
AnnDan
EricPam
HDHDHD
Punnett Square
+ = wild typeallele
HD = Huntingtondisease allele
+ HDAffected parent
+ +Unaffected parent
For eachIndividualconceived:
50% chanceunaffected
50% chanceaffected
+ + + HD
• Autosomal Dominant Inheritance
• 1:1 Phenotype• 1:1 Genotype
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Different Dominance Relationships
• Incomplete dominance• Heterozygote has a
phenotype intermediate between homozygous dominant and homozygous recessive
• Familial hypercholesterolemia is an example here
• Most genes exhibit complete dominance or recessiveness• Exceptions are incomplete dominance and codominance
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Heterozygotesfor FH
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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.
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• 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
Different Dominance Relationships
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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
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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
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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
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Genetic Heterogeneity
• Genetic heterogeneity• The same phenotype resulting from the actions of different genes• Hereditary deafness is an example
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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
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(a)
(b)
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a: © Library of Congress; b: © Peter Morenus/University of Connecticut at Storrs
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Number of dominant alleles
Fre
qu
ency
0 1 2 3 4 5 6
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AABB AABb AaBB
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Number ofdominant
alleles
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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
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+ +
X
Egg
X
Egg
YX
X-bearingsperm
Y-bearingsperm
XXfemale
XYmale
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Sex Determination
• 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
X chromosome
SRY gene
Y chromosome
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© Biophoto Associates/Photo Researchers, Inc.
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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
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• 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
Hemophilia
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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
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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
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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
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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
Monosomic Monosomic Euploid Euploid Monosomic
Zygotes
Meiosis II
A A a a
A A a a A A a a
Meiosis I
(a) (b)
A A a a
A a A a a aA A
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First divisionnondisjunction
Primary spermatocyte
Secondaryspermatocyte
Sperm
Seconddivisionnondisjunction
Fertilization ofeuploid egg
Trisomic Trisomic Trisomic 32
• 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
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Prenatal Tests Detect Chromosome Abnormalities
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Prenatal Tests Detect Chromosome Abnormalities
Placenta
Catheter
Fetus
Cervix
Syringe
(a) Chorionic villus sampling
Uterus
(c) Fetal cell sorting
Rare fetal cells
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Chorionicvilli
Vagina
Amnioticmembrane
Fetus15–16weeks
(b) Amniocentesis
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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
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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.
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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.
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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.
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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.