Outline of Lecture Ch 14, Part II 1. Extending simple Mendelian genetics a. The spectrum of dominance b. More than 2 alleles c.

. Pleiotropy d. Epistasis e. Polygenic inheritance 2. Human Genetics and Disease Practice questions up Wednesday, Review Monday in LFSC UNLH 1000 6:10 (Paine) 9:00 p.m. (Morse starts midway) Paine & Morse office hours: T, W 2:10-4 1!

Concept 14.3: Inheritance patterns are often more complex than predicted by simple Mendelian genetics The relationship between genotype and phenotype is rarely as simple as in the pea plant characters Mendel studied Many heritable characters are not determined by only one gene with two alleles However, the basic principles of segregation and independent assortment apply even to more complex patterns of inheritance
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Extending Mendelian Genetics for a Single Gene

Inheritance of characters by a single gene may deviate from simple Mendelian patterns in the following situations: When alleles are not completely dominant or recessive When a gene has more than two alleles When a gene produces multiple phenotypes

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Dominance

The characters Mendel worked with have a relatively simple genetic basis: 1. One gene locus at a time 2. Only two alleles 3. One allele is completely dominant to the other

Table 14.1 complete dominance =

A type of inheritance in which the phenotype of the heterozygous genotype and the phenotype of the dominant homozygous genotype are indistinguishable.

The Spectrum of Dominance !

Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identical! In incomplete dominance, the phenotype of F1 hybrids (of homozygous parents) is somewhere between the phenotypes of the two parental varieties! In codominance, two dominant alleles affect the phenotype in separate, distinguishable ways!
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Incomplete dominance in snapdragons

CW P C RC R CWCW
R R W

CW
R

W C C C C C

C R C RC W C RC W

F1

C RC W 100% CR CW
R R

F2 C RC R 25%
See Figure 14.10

C C RC W 50% CWCW 25%

C C C CW

R W CW C C CWCW

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Dominance
How does incomplete dominance differ from blending inheritance?

Homozygous,

C C

Homozygous,

C C

Heterozygous,

C C
Flower color in snapdragons (Antirrhinum sp.)

A type of inheritance in which the phenotype of the incomplete dominance = heterozygous genotype is intermediate between the phenotypes of the two homozygous genotypes.

Multiple Alleles!
Most genes exist in populations in more than two allelic forms! For example, the four phenotypes of the ABO blood group in humans are determined by three alleles for the enzyme (I) that attaches A or B carbohydrates to red blood cells: IA, IB, and i.! The enzyme encoded by the IA allele adds the A carbohydrate, whereas the enzyme encoded by the IB allele adds the B carbohydrate; the enzyme encoded by the i allele adds neither!
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Blood types = codominance, > 2 alleles

See Fig. 14.11

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Codominance: both alleles are fully expressed in the heterozygote

ABO Blood Types in Humans

Red blood cells may have surface carbohydrates of type A, type B, or neither.

A and B are codominant.

i is recessive to A and B.
See Fig. 14.11

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Pleiotropy
Function 1: transports vitamin A Function 2: absorbs UV light

CRBP1 (cellular retinol binding protein I)

gecko sunglasses

typical night gecko lizard

Lygodactylus-day gecko lizard

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Sickle-Cell Disease (recessive genetic disorder)

Sickle-cell disease affects one out of 400 AfricanAmericans The disease is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells Symptoms include physical weakness, pain, organ damage, and even paralysis

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Pleiotropy =
The situation in which a single gene has multiple phenotypic effects
Heterozygous individuals ALSO have resistance to several forms of malaria Sickle cell disease See pp. 277-278

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Epistasis!
In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus! For example, in mice and many other mammals, coat color depends on two genes! One gene determines the pigment color (with alleles B for black and b for brown)! The other gene (with alleles C for pigment color and c for no pigment color ) determines whether the pigment will be deposited in the hair !
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Fig. 14.12 (Labs also)

Gene 1, pigment color

B - Dominant, black b - recessive, brown

Gene 2, pigment deposition

C - Dominant, pigment deposited c - recessive, no pigment

gene 2 is epistatic to gene 1 Epistasis =

A phenomenon in which a gene at one locus influences the phenotypic expression of a gene at another locus.

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How Mendel did his Genetic Crosses

Trait 1

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- Mendel solely used qualitative characters = either this or that (no intermediates) - Mendel ignored quantitative characters = more or less Characters (vary along a continuum)

Trait 2

Table 14.1

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Polygenic Inheritance!
Quantitative characters are those that vary in the population along a continuum! Quantitative variation usually indicates polygenic inheritance, an additive effect of two or more genes on a single phenotype! Skin color in humans is an example of polygenic inheritance!
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AaBbCc

AaBbCc

See Fig. 14.13 Human skin color at least 3 separate genes are involved
Fraction of progeny

aabbcc
20/64

Aabbcc

AaBbcc AaBbCc AABbCc AABBCc AABBCC

15/64

6/64

1/64

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Theories Regarding Human Skin Color Evolution

Ancient relatives of humans had light colored skin and dense, dark body hair Massive drought ca. 1.5 mya drove hominids from lush rainforests into much more arid and open environments Gradual evolution towards loss of hair (heat dissipation); skin color darkened due to the intense radiation of the African sun (folate depletion with increased sunlight exposure) Folate is critical to a healthy pregnancy; can result in anemia; helps prevent illness and kidney/liver disease Ca. 115,000 years ago, humans started migrating out of Africa

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Theories Regarding Human Skin Color Evolution

As humans moved further from the equator, much less selection to maintain protective dark skin coloration Selection against dark skin color in northern populations due to limited production of Vitamin D Vitamin D critical to proper absorption of calcium (bone health, other impacts) and phosphorous can be a problem for people living in the Pacific Northwest Genetic mutations leading to lighter skin color occurred twice separately in Europeans and East Asians

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Integrating a Mendelian View of Heredity and Variation!

An organisms phenotype includes its physical appearance, internal anatomy, physiology, and behavior! An organisms phenotype reects its overall genotype and unique environmental history!

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Nature and Nurture: The Environmental Impact on Phenotype Another departure from Mendelian genetics arises when the phenotype for a character depends on environment as well as genotype The norm of reaction is the phenotypic range of a genotype influenced by the environment For example, hydrangea flowers of the same genotype range from blue-violet to pink, depending on soil acidity
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Same variety of hydrangea flower - soil acidity

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Concept 14.4: Many human traits follow Mendelian patterns of inheritance!

Humans are not good subjects for genetic research because generation time is too long; parents produce relatively few offspring; and breeding experiments are unacceptable! However, basic Mendelian genetics endures as the foundation of human genetics!
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Pedigree Analysis

A pedigree is a family tree that describes the interrelationships of parents and children across generations Inheritance patterns of particular traits can be traced and described using pedigrees

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Fig. 14-15b

First generation (grandparents)

Ff

Ff

ff

Ff

Second generation (parents plus aunts and uncles)

FF or Ff ff

ff

Ff

Ff

ff

Third generation (two sisters)

ff

FF or Ff

Attached earlobe Recessive trait (attached earlobe)

Free earlobe

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Frequency of Dominant Alleles!

Dominant alleles are not necessarily more common in populations than recessive alleles! For example, one baby out of 400 in the United States is born with extra ngers or toes! The allele for this unusual trait is dominant to the allele for the more common trait of ve digits per appendage! In this example, the recessive allele is far more prevalent than the dominant allele in the population!
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Examples of human diseases caused by single locus mutations

Type of inheritance
Dominant

Disease/disorder

Symptoms

Achondroplasia Glaucoma Huntingtons disease Hypercholestrolemia Polydactyly

Dwarfism Blindness Degeneration of the nervous system Early-onset high blood cholesterol Extra fingers and toes

> 2000 human diseases or disorders are caused by singlelocus dominant alleles. > 1300 human diseases or disorders are caused by singlelocus recessive alleles.

Recessive

Cystic fibrosis Galactosomia Phenylketonuria Sickle-cell disease Tay-Sachs disease

Thick, sticky intracellular mucus Inability to digest lactose Liver enzyme deficiency mental retardation Anemia Build up of lipids in the brain

Sex-linked

Aggamaglobulinemia Color blindness Hemophilia

Lack of resistance to infection

~ 1 Inability to babies in the US is born with extra in 400 distinguish red/green Reduced toes. So fingers or blood-clotting 399 in 400 babies are homozygous recessive for this character.

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Recessively Inherited Disorders

Many genetic disorders are inherited in a recessive manner Recessively inherited disorders show up only in individuals homozygous for the allele Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal

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Cystic Fibrosis (recessive genetic disorder)

Cystic fibrosis is the most common lethal genetic disease in the United States,striking one out of every 2,500 people of European descent The cystic fibrosis allele results in defective or absent chloride transport channels in plasma membranes Symptoms include mucus buildup in some internal organs and abnormal absorption of nutrients in the small intestine

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Mating of Close Relatives

Matings between relatives can increase the probability of the appearance of a genetic disease Such mating are more likely to produce offspring with homozygosity for deleterious recessive genes Often seen in purebred domesticated animals and zoo populations

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Multifactorial Disorders
Many diseases, such as heart disease and cancer, have both genetic and environment components Little is understood about the genetic contribution to most multifactorial diseases

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Newborn Screening
Some genetic disorders can be detected at birth by simple tests that are now routinely performed in most hospitals in the United States In amniocentesis, the liquid that bathes the fetus is removed and tested Other techniques, ultrasound and fetoscopy, allow fetal health to be assessed visually in utero

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Practice Question (Similar to Ch. 14, Q 11)

Genotypes of F1s of both sexes in a tetrahybrid cross are AaBbccDd. Assuming independent assortment, what is the probability F2 offspring will be (a) aabbccdd or AABBccDD; (b) AaBBccdd; (c) AaBbccDd!

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Practice Question (Ch. 14, Q 19, modified)

Charles and his former wife had a child; the child had cystic brosis. His new wife, Elaine, had a brother who died of cystic brosis. Neither Charles, Elaine, or their two children have cystic brosis. What are the odds their third child will have this disease (neither of Elaines parents had cf)? !
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