3.4: Inheritance

*Define "mutagen."* Understanding: Radiation and mutagenic chemicals increase the mutation rate and can cause genetic diseases and cancer.

*A mutagen is a chemical or physical agent that causes mutations.* Mutagens cause mutations in three different ways: 1. Some are mistakenly used as bases when new DNA is synthesized at the replication fork. 2. Some react directly with DNA, causing structural changes that lead to miscopying of the template strand when the DNA is replicated. 3. Some mutagens act indirectly on DNA. They do not themselves affect DNA structure, but instead cause the cell to synthesize chemicals that have a direct mutagenic effect.

*Explain how to deduce an autosomal dominant inheritance pattern in a pedigree chart.​* Skill: Analysis of pedigree charts to deduce the pattern of inheritance of genetic diseases.

*Autosomal Dominant* Appear equally in males and female Does not skip generations Affected offspring have an affected parent

*Explain how to deduce an autosomal recessive inheritance pattern in a pedigree chart.​* Skill: Analysis of pedigree charts to deduce the pattern of inheritance of genetic diseases.

*Autosomal Recessive* Appear equally in males and female Can skip generations

*List example genetic diseases with their inheritance pattern.* Understanding: Many genetic diseases have been identified in humans but most are very rare.

*Cystic fibrosis* - autosomal recessive *Stargardt’s disease* - autosomal recessive *Hemophilia* - sex linked recessive *Huntington's disease* - autosomal dominant *Phenylketonuria (PKU)* - autosomal recessive *Red-green color blindness* - sex linked recessive

*Explain how to deduce an X-linked recessive inheritance pattern in a pedigree chart.​* Skill: Analysis of pedigree charts to deduce the pattern of inheritance of genetic diseases.

*X-linked Recessive* Appear much more frequently in males Can skip generations Mothers of affected sons are carriers

*Construct Punnett grids for single gene crosses to predict the offspring genotype and phenotype ratios.* Skill: Construction of Punnett grids for predicting the outcomes of monohybrid genetic crosses.

1. Create a key for the allele identification 2. Draw a 2 x 2 square 3. Label the rows with one parent's possible alleles in the gametes 4. Label the columns with the other parent's possible alleles in the gametes 5. Have each box "inherit" alleles from its row and column. 6. Interpret the Punnett square, summarizing the percent offspring with each phenotype.

*Using a Punnett grid, deduce the probability of a child inheriting an autosomal recessive disease, if both of the parents are carriers of the disease but do not have the disease themselves..* Skill: Construction of Punnett grids for predicting the outcomes of monohybrid genetic crosses.

1. Create a key for the allele identification (S dominant; s recessive) 2. Draw a 2 x 2 square 3. Label the rows with one parent's possible alleles in the gametes (Ss) 4. Label the columns with the other parent's possible alleles in the gametes (Ss) 5. Have each box "inherit" alleles from its row and column. 6. Interpret the Punnett square, summarizing the percent offspring with each phenotype (3 normal : 1 with disease)

*Construct Punnett grids for sex linked crosses to predict the offspring genotype and phenotype ratios.* Understanding: The pattern of inheritance is different with sex-linked genes due to to their location on sex chromosomes.

1. Create a key to the alleles using correct notation (XY with superscript alleles on the X) 2. Draw a 2 x 2 square 3. Label the rows with one parent's genotype, using the notation for sex linked genes 4. Label the columns with the other parent's genotype, using the notation for sex linked genes 5. Have each box "inherit" alleles from its row and column. 6. Interpret the Punnett square, summarizing the percent of males and females with each phenotype.

*Describe why it is not possible to be a carrier of a disease caused by a dominant allele.* Understanding: Some genetic diseases are sex-linked and some are due to dominant or codominant alleles.

A carrier is an individual with a heterozygous genotype, carrying the disease allele but not showing the disease phenotype. If the disease is due to a dominant allele, the individual will show the disease phenotype when heterozygous.

*Define "gamete."* Understanding: Gametes are haploid so contain only one allele of each gene.

A gamete is a reproductive cell, egg or sperm. Gametes are haploid; containing a single set of unpaired chromosomes.

*Define "carrier" as related to genetic diseases.* Understanding: Many genetic diseases in human are due to recessive alleles of autosomal genes.

A genetic carrier is an individual that has inherited a recessive allele of a gene but does not display the symptoms of the disease because they also have the dominant (normal functioning) allele. Carriers are heterozygous.

*Define "monohybrid."* Skill: Construction of Punnett grids for predicting the outcomes of monohybrid genetic crosses.

A monohybrid cross is a genetic cross between two individuals, tracking one gene of interest.

*Define "mutation" as related to genetic diseases and cancer.* Understanding: Radiation and mutagenic chemicals increase the mutation rate and can cause genetic diseases and cancer.

A mutation is the permanent alteration of the nucleotide sequence of the genome of an organism.

*Outline the conventions for constructing pedigree charts.* Skill: Analysis of pedigree charts to deduce the pattern of inheritance of genetic diseases.

A pedigree chart is a diagram that shows the occurrence of a phenotype in generations of a family. Male = square Female = circle Shaded = affected

*State the maximum number of alleles in a diploid zygote.* Understanding: Fusion of gametes results in diploid zygotes with two alleles of each gene that may be the same allele or different alleles.

Alleles are variations of a single gene. Although there usually are multiple alleles for a gene in the population, any single individual can only have a maximum of two alleles of a gene, one allele on each chromosome of a homologous pair.

*State two similarities and two differences between male and female gametes.* Understanding: Gametes are haploid so contain only one allele of each gene.

Both egg and sperm are haploid (23 chromosomes in humans) cells produced through meiosis. The egg and sperm are very different in size and shape. Eggs are large cells; sperm are much smaller. Sperm have flagella, egg do not.

*Outline the effects of gene mutations in body cells and gamete cells.* Understanding: Radiation and mutagenic chemicals increase the mutation rate and can cause genetic diseases and cancer.

Cell damage and death that result from mutations in somatic cells occur only in the organism in which the mutation occurred and are therefore termed somatic or non heritable effects. Cancer is the most notable long-term somatic effect. In contrast, mutations that occur in germ line cells (which become gametes, sperm and egg) can be transmitted to future generations and are therefore called genetic or heritable effects. Genetic effects may not appear until many generations later.

*Outline the inheritance pattern of cystic fibrosis.* Application: Inheritance of cystic fibrosis and Huntington's disease.

Cystic fibrosis is *autosomal recessive.* Autosomal: the gene is located on an autosome, NOT a sex chromosome Recessive: to have CF, males and females need to inherit two mutated alleles (one from each parent)

*Define "dominant allele."* Understanding: Dominant alleles mask the effect of recessive alleles but codominant alleles have joint effects.

Different versions of a gene are called alleles. *Dominant alleles* show their effect even if the individual is heterozygous, they can *mask the presence of another allele.*

*Define "recessive allele."* Understanding: Dominant alleles mask the effect of recessive alleles but codominant alleles have joint effects.

Different versions of a gene are called alleles. *Recessive alleles* only show their effect if the individual has two copies (homozygous recessive), otherwise *their presence can be masked by a dominant allele.*

*Outline the possible combination of alleles in a diploid zygote for a gene with two alleles.* Understanding: Fusion of gametes results in diploid zygotes with two alleles of each gene that may be the same allele or different alleles.

For a gene with two alleles, the zygote could be either: *homozygous dominant:* two copies of the dominant allele (i.e. AA) *heterozygous:* one copy of the dominant allele and one copy of the recessive allele (i.e. Aa) *homozygous recessive:* two copies of the recessive allele (i.e. aa)

*Describe the pattern of inheritance for sex linked genes.* Understanding: The pattern of inheritance is different with sex-linked genes due to to their location on sex chromosomes.

Genes that are located on just one of the sex chromosomes are sex-linked. Common examples are colorblindness and hemophilia. Because males only have one X-chromosome, genes on the X are expressed in the male phenotype. If the male has a recessive allele for an X-linked gene, it will be expressed because there isn't a second X chromosome with another allele that could mask the recessive allele. As a result, sex-linked conditions tend to be more commonly expressed in males. Females can be homozygous or heterozygous for a sex-linked condition. In heterozygous females, a recessive allele on the X chromosome can be masked by a dominant allele on the other X chromosome. Heterozygous females are called "carriers" because they carry the allele but do not express the condition.

*Define "haploid."* Understanding: Gametes are haploid so contain only one allele of each gene.

Haploid cells contain a single set of unpaired chromosomes and therefore only one allele of each gene.

*Explain inheritance patterns of hemophilia.* Application: Red-green color blindness and hemophilia as examples of sex-linked inheritance.

Hemophilia is *X-linked recessive.* X-linked: the gene is located on the X chromosome Recessive: to be hemophiliac, males only need one mutated allele, females need two mutated alleles (which is exceedingly rare)

*Describe the cause and effect of hemophilia.* Application: Red-green color blindness and hemophilia as examples of sex-linked inheritance.

Hemophilia is caused by a mutated allele of a gene that codes for a essential protein in the blood clotting process. Without proper clotting, hemophiliacs are prone to excessive bleeding.

*Outline the effects of radiation exposure after nuclear exposure at Hiroshima.* Application: Consequences of radiation after nuclear bombing of Hiroshima and accident at Chernobyl.

Hiroshima was the site of an atomic bomb at the end of WWII (1945). Thousands of people died instantly and many others suffered effects of radiation poisoning (hair loss, bleeding, vomiting and diarrhea).

*Outline the inheritance pattern of Huntington's disease.* Application: Inheritance of cystic fibrosis and Huntington's disease.

Huntington's disease is *autosomal dominant.* Autosomal: the gene is located on an autosome, NOT a sex chromosome Dominant: to have Huntington's, males and females only need to inherit one mutated allele.

*Outline inheritance patterns of genetic diseases caused by dominant alleles.* Understanding: Some genetic diseases are sex-linked and some are due to dominant or codominant alleles.

In the case of a disease caused by a dominant allele, only one copy of the disease allele is needed for the individual to express the disease phenotype. If a parent is homozygous dominant, there is a 100% chance the offspring will inherit the allele and express the genetic disease. If a parent is heterozygous, there is a 50% chance the offspring will inherit the allele. All affected individuals will have at least one parent with the disease.

*List biological research methods pioneered by Mendel.* Nature of Science: Making quantitative measurements with replicates to ensure reliability, Mendel's genetic crosses with peas plants generated numerical data.

Large number of replicates to demonstrate reliability of results. Repeats of whole experiments. Obtaining quantitative results, not only qualitative descriptions.

*Outline the possible combination of alleles in a diploid zygote for a gene with three alleles.* Understanding: Fusion of gametes results in diploid zygotes with two alleles of each gene that may be the same allele or different alleles.

Many genes have multiple alleles within the *population*. For example, in ABO blood typing there are three common alleles for the Isoagglutinogen gene: I^A, I^B and i. Within a diploid *individual* there may only be a combination of two of the alleles: I^A, I^A (type A) I^A, I^B (type AB) I^A, i (type A) I^B, I^B (type B) I^B, i (type B) i, i (type O)

*State the outcome of allele segregation during meiosis.* Understanding: The alleles of each gene separate into different haploid daughter nuclei during meiosis.

Mendel's Law of Segregation states that a pair of alleles (variations of the same gene) separate into different gamete cells during meiosis.

*Outline why Mendel's success is attributed to his use of pea plants.* Nature of Science: Making quantitative measurements with replicates to ensure reliability, Mendel's genetic crosses with peas plants generated numerical data.

Mendel's use of peas allowed for the observation of *easily distinguishable characteristics* (i.e. yellow or green pods). Also, the peas were able to *reproduce quickly* allowing for many generations of data to be collected. Lastly, the *reproduction could be controlled,* so Mendel knew exactly which two parent plants were being bred (either cross-bred or self-pollination).

*Explain why most genetic diseases are rare in a population.* Understanding: Many genetic diseases have been identified in humans but most are very rare.

Most genetic diseases are caused by alleles that are rare in the population. In the case of an autosomal recessive disease, a person must inherit two copies of a rare allele (one from each parent).

*Explain why genetic diseases are rare and usually appear unexpectedly in a population.* Understanding: Many genetic diseases in human are due to recessive alleles of autosomal genes.

Often times genetic diseases seem to just "appear" in a family without prior history. This is usually because the disease is caused by a recessive allele that has been masked by dominant alleles. If two carriers, who show no disease symptoms, produce offspring, there is a 1/4 change of the offspring showing the disease characteristics.

*Explain inheritance patterns of red-green color blindness.* Application: Red-green color blindness and hemophilia as examples of sex-linked inheritance.

Red-green color blindness is *X-linked recessive.* X-linked: the gene is located on the X chromosome Recessive: to be colorblind, males only need one mutated allele, females need two mutated alleles

*Describe the cause and effect of red-green color blindness.* Application: Red-green color blindness and hemophilia as examples of sex-linked inheritance.

Red-green color blindness is caused by a sex linked recessive allele of a gene that codes for a protein (opsin) in the eye that is sensitive to particular wavelengths of light. The mutated allele causes red-green color vision defects.

*Define "sex linkage."* Understanding: Some genetic diseases are sex-linked and some are due to dominant or codominant alleles.

Sex linkage refers to genes located on the sex chromosomes, X or Y. The genes expression, inheritance pattern and effect on the phenotype will differ between males and females.

*Explain sickle cell anemia as an example of a genetic disease caused by codominant alleles.* Understanding: Some genetic diseases are sex-linked and some are due to dominant or codominant alleles.

Sickle cells anemia is a rare disease where red blood cells become thin and elongated. If a person has one copy of the sickle cell allele, half of their red blood cells will be misshapen. The alleles are codominant since both normal and sickle cell shapes are seen in a heterozygous individual.

*Using the correct notation, outline an example of codominant alleles.* Understanding: Dominant alleles mask the effect of recessive alleles but codominant alleles have joint effects.

Since there isn't a true dominant allele, a lowercase letter is NOT used when alleles are codominant. Rather, two different capital letters are used and places as superscript next to a common letter that represents the name of the gene. For example, type A and type B alleles of the Isoagglutinogen gene. I^A and I^B are codominant.

*Describe the role of statistical tests in deciding whether an actual result is a close fit to a predicted result.* Skill: Comparison of predicted and actual outcomes of genetic crosses using real data.

Statistics, such as the chi-square test, allow us to determine the probability of observing a discrepancy between observed (actual results) and expected (predicted results). In other words, statistics *help us determine the chance of getting the observed results given what was expected.*

*Describe inheritance of ABO blood types.* Application: Inheritance of ABO blood groups.

The ABO blood groups are determined by the Isoagglutinogen gene. The gene codes for an enzyme protein that modifies the carbohydrate molecule attached to a protein on the surface of red blood cells. The I gene has three alleles: I^A, I^B and i. Alleles I^A and I^B are completely dominant over allele i. So: I^A, i (type A) I^B, i (type B) Alleles I^A and I^B are codominant, so bother are expressed in a heterozygous individual: I^A, I^B (type AB)

*Define "F2" as related to genetic crosses.* Skill: Construction of Punnett grids for predicting the outcomes of monohybrid genetic crosses.

The F2 generation is the result of a cross between two F1 individuals.

*Explain the reason why the outcomes of genetic crosses do not usually correspond exactly with the predicted outcomes.* Skill: Comparison of predicted and actual outcomes of genetic crosses using real data.

The actual outcomes of a genetic cross may not exactly match outcomes predicted based on a Punnett square because *there is an element of chance* in the segregation of alleles and fertilization.

*State the usual cause of one allele being dominant over another.* Understanding: Dominant alleles mask the effect of recessive alleles but codominant alleles have joint effects.

The cause of allele dominance is complex and can vary between genes. However, in general, the dominant allele codes for a functioning proteins whereas the recessive allele codes for a less (or non-) functioning protein. Sometimes the recessive allele is the "normal" or "healthy" version of the gene.

*Define "F1" as related to genetic crosses.* Skill: Construction of Punnett grids for predicting the outcomes of monohybrid genetic crosses.

The offspring of a cross between two parent organisms, "first filial."

*Explain how to determine possible alleles present in gametes given parent genotypes.* Skill: Construction of Punnett grids for predicting the outcomes of monohybrid genetic crosses.

The parent genotype consists of two alleles. During meiosis, these alleles segregate into gametes with equal probability.

*Define "zygote."* Understanding: Gametes are haploid so contain only one allele of each gene.

The zygote is the diploid cell that results from the fusion of two haploid gametes during fertilization.

*Outline the effects of radiation exposure after nuclear exposure at Chernobyl.* Application: Consequences of radiation after nuclear bombing of Hiroshima and accident at Chernobyl.

There was an accidental explosion at the Chernobyl nuclear power plant in the USSR (1986). Many people died or developed cancer as a result of the radiation exposure.

*Outline Thomas Hunt Morgan's discovery of sex linked genes with Drosophila.* Understanding: The pattern of inheritance is different with sex-linked genes due to to their location on sex chromosomes.

Thomas Hunt Morgan studied genetics of fruit flies, Drosophila. He discovered sex-linked traits; traits that appear to associate differently in males and females. Flies normally have red eyes, but there was a mutant male with white eyes. This white-eyed male was crossed with a red eyed female (P generation). All offspring (F1 generation) were red-eyed therefore *red is dominant over white.* Then, two of the red-eyed offspring were crossed (F1 X F1). In the offspring (F2), only males had white eyes, suggesting that the *eye-color allele is carried on the X-chromosome.*

*Describe conclusions drawn from Mendel's pea plant experiments.* Understanding: Mendel discovered the principles of inheritance with experiments in which large numbers of pea plants were crossed.

Through selective breeding of pea plants, Mendel discovered that certain traits show up in offspring without blending of the parent's characteristics. Mendel observed seven traits: flower color, stem length, seed color, pod color, flower position, seed shape and pod shape. Mendel concluded: 1. *genetic "units" of inheritance are passed from parents to offspring* 2. *the offspring inherits one "unit" from each parent for each trait.* 3. *the "unit" may be masked or hidden (i.e. recessive) in an individual but can still be passed on to the next generation.*

*Define "true breeding."* Skill: Construction of Punnett grids for predicting the outcomes of monohybrid genetic crosses.

True breeding organisms are those that have been bred to have a homozygous genotype.

*Outline the effect of radiation on the structure of DNA.* Understanding: Radiation and mutagenic chemicals increase the mutation rate and can cause genetic diseases and cancer.

UV and ionizing radiation alters chemical bonds and may result in a change to the DNA sequence. The mutation is a random process. Cancer is produced if radiation does not kill the cell but creates an error in the DNA blueprint that contributes to eventual loss of control of cell division, and the cell begins dividing uncontrollably. This effect might not appear for many years.

*Define "codominant alleles."* Understanding: Dominant alleles mask the effect of recessive alleles but codominant alleles have joint effects.

With codominant alleles, both alleles are expressed equally; there isn't masking of a recessive by a dominant allele.

*Summarize the correct notation for sex linked genes.* Understanding: The pattern of inheritance is different with sex-linked genes due to to their location on sex chromosomes.

With sex linked traits, the X and Y chromosome are shown with symbols for the dominant and recessive alleles written as superscripts next to the chromosome.