MCBG Session 7 - Genotype, Phenotype, Inheritance Flashcards
What is a pedigree and what is its value?
- A pedigree is a diagram showing genetic information from a family, using standardized symbols.
- Analysis of pedigrees using knowledge of Mendelian principles has two initial goals:
I. To determine whether the trait has a dominant or a recessive pattern of inheritance
II. To discover whether the gene in question is located on an X or a Y chromosome or on an autosome
Why is it important to establish how a trait is inherited?
- For several reasons, it is important to establish how a trait is inherited.
- If the pattern of inheritance can be established, it can be used to predict genetic risk in several situations, including:
I. Pregnancy outcomes
II. Adult-onset disorders
III. Recurrence risks in future off spring
What are the five basic Mendelian patterns of inheritance for traits controlled by single genes?
- Autosomal recessive inheritance
- Autosomal dominant inheritance
- X-linked dominant inheritance
- X-linked recessive inheritance
- Y-linked inheritance
- In addition, there is a distinctive non-Mendelian pattern of inheritance observed in traits controlled by single genes encoded by mitochondrial genes
Outline Paternal inheritance: Genes on the Y chromosome.
- Because only males have Y chromosomes, traits encoded by genes on the Y are passed directly from father to son and have a unique pattern of inheritance.
- In addition, all Y-linked traits should be expressed because males are hemizygous for all genes on the Y chromosome.
- To date, only about three dozen Y-linked traits have been discovered, most of which are involved in male sexual development.
- One of these, testis-determining factor (TDF/SRY; OMIM 480000), is involved in determining maleness in developing embryos.
Outline autosomal recessive traits.
Recessive traits carried on autosomes have several distinguishing characteristics:
- For rare or relatively rare traits, affected individuals have unaffected parents.
- All the children of two affected (homozygous) individuals are affected.
- The risk of an affected child from a mating of two heterozygotes is 25%.
- Because the trait is autosomal, it is expressed in both males and females, who are affected in roughly equal numbers. Both the male and the female parent will transmit the trait.
Outline and identify some examples of autosomal recessive traits.
- Albinism - the absence of pigment in skin, eyes, hair
- Cystic fibrosis - mucous production that blocks the ducts of certain glands, lung passages; often fatal by early adulthood
- Galactosaemia - accumulation of galactose in the liver; mental retardation
- Phenylketonuria - excess accumulation of phenylaline in blood; mental retardation
- Sickle cell anaemia - abnormal haemoglobin; blood vessel blockage; early death
- Thalassemia - improper haemoglobin production; symptoms range from mild to fatal
- Xeroderma pigmentosum - lack od DNA repair enzymes, sensitivity to UV light; skin cancer, early death
Outline autosomal dominant traits.
In autosomal dominant disorders, heterozygotes have an abnormal phenotype. Unaffected individuals carry two recessive alleles and have a normal phenotype. Dominant traits have a distinctive pattern of inheritance and usually have affected family members in each generation:
- Every affected individual has at least one affected parent. Exceptions occur when the gene has a high mutation rate. (Mutation is a heritable change in a gene.)
- Most affected individuals are heterozygotes with a homozygous recessive (unaffected) spouse, so each child has a 50% chance of being affected.
- Because the trait is autosomal, the numbers of affected males and females are roughly equal.
- Two affected individuals may have unaffected children (because most affected individuals are heterozygous).
- The phenotype in homozygous dominant individuals is often more severe than the heterozygous phenotype.
Outline and identify some examples of autosomal recessive traits.
- Achondroplasia - dwarfism associated with defects in growth regions of long bones
- Ehlers-Danlos syndrome - connective tissue disorder, elastic skin, loos joints
- Marfan syndrome - connective tissue defect, death by aortic rupture
- Huntington disease - progressive degeneration of nervous system, dementia, early death
- Familial hypercholesterolaemia - elevated levels of cholestrol; predisposes to plaque formation, cardiac disease, may be most prevalent genetic disease
Provide a general outline for the sex-linked inheritance.
- The X and Y chromosomes are called sex chromosomes because they play major roles in determining the sex of an individual.
- Genes on the X chromosome are called X-linked, and genes on the Y chromosome are called Y-linked.
- Female humans have two X chromosomes and, therefore, two copies of all X-linked genes and can be heterozygous or homozygous for any of them.
- Males, in contrast, are XY and carry only one copy of the X chromosome.
- Most genes on the X chromosome are not found on the Y chromosome.
- This means that males carrying a gene for a recessive disorder such as haemophilia or colour blindness cannot carry a dominant allele to mask expression of the recessive allele.
- This explains why males are affected by X-linked recessive genetic disorders far more often than are females.
What does it mean to be hemizygous?
Because a male cannot be homozygous or heterozygous for genes on the X chromosome, males are said to be hemizygous - A gene present on the X chromosome that is expressed in males in both the recessive and the dominant conditions - for all genes on the X chromosome.
Outline the inheritance of Dominant X-linked traits.
Only a small number of dominant traits are carried on the X chromosome. Dominant X-linked traits have a distinctive pattern of inheritance:
- Affected males transmit the trait to all their daughters but none of their sons.
- A heterozygous affected female will transmit the trait to half of her children, with sons and daughters affected equally.
- On average, twice as many females are affected as males (females can be heterozygous or homozygous).
Outline the inheritance of recessive X-linked traits.
These two factors produce a distinctive pattern of inheritance for X-linked recessive traits. This pattern can be summarized as follows:
- Hemizygous males and females homozygous for the recessive allele are affected.
- Phenotypic expression is much more common in males than in females. In the case of rare alleles, males are almost exclusively affected.
- Affected males receive the mutant allele from their mothers and transmit it to all their daughters but not to any of their sons.
- Daughters of affected males are usually heterozygous and therefore unaffected, but sons of heterozygous females have a 50% chance of receiving the recessive gene.
Outline non-mendelian inheritance: maternal mitochondrial genes.
- Mitochondria are cellular organelles transmitted from mothers to all their children through the cytoplasm of the egg (sperm do not contribute mitochondria at fertilization).
- As a result, genetic disorders caused by mutations in mitochondrial genes have the following properties:
I. They are maternally inherited and produce a distinctive pattern of inheritance.
II. All the children of affected females are affected. Affected females will transmit the disorder to all their off spring, but affected males cannot transmit the mutations to any of their children
Outline the effects of mitochondrial disorder.
- Because mitochondria are energy producers, mutations in mitochondrial genes reduce the amount of energy available for cellular functions.
- As a result, the phenotypic effects of mitochondrial disorders can be highly variable.
- In general, tissues with the highest energy requirements are affected most often. These include muscles and the nervous system.
- Disorders that mainly affect the muscles are grouped together and called mitochondrial myopathies. Those that affect both muscles and the nervous system are called mitochondrial encephalomyopathy.
Explain mendelian inheritance by independent assortment.
- The inheritance of two traits in humans also follows the Mendelian principle of independent assortment.
EXAMPLE:
To illustrate, let’s examine a family in which the parents are each heterozygous for albinism (Aa) and heterozygous for hereditary deafness (OMIM 220290), another recessive trait.
- Homozygous dominant (DD) or heterozygous individuals (Dd) can hear, but homozygous recessive (dd) individuals are deaf.
- During meiosis, alleles for skin color and alleles for hearing assort into gametes independently.
- As a result, each parent produces equal proportions of 4 diff erent gametes (AD, Ad, aD, and ad).
- There are 16 possible combinations of gametes at fertilization (4 types of gametes in all possible combinations), resulting in 4 diff erent phenotypic classes.
- An examination of the possible genotypes shows that there is a 1 in 16 chance that a child will be both deaf and an albino.
What is incomplete dominance?
EXAMPLE
- Incomplete dominance has a distinctive phenotype in heterozygotes.
- One case in which phenotypes do not follow the predicted ratios for a Mendelian trait is the inheritance of flower color in snapdragons.
- If snapdragons with red flowers are crossed with plants carrying white flowers, the F1 will have pink flowers.
- In this case, the F1 phenotype is intermediate to the parental phenotypes, and neither the red nor the white color is dominant. T
- his condition is called incomplete dominance – expression of a phenotype that is intermediate to those of the parents.
- In snapdragons, flower color is controlled by a single gene, with two alleles. Because neither allele is recessive, we will call the alleles R1 (red) and R2 (white).
What is codominance?
- In some cases, both alleles in a heterozygote are fully expressed. This situation is called codominance.
EXAMPLE
- In humans, the MN blood group is an example of this phenomenon.
- The MN blood group is controlled by a single gene, L, which directs the synthesis of a glycoprotein, found on the surface of red blood cells and other cells of the body.
- This gene has two alleles: LM and LN. Each allele directs the synthesis of a diff erent form of glycoprotein.
- Depending on genotype, an individual may carry the M glycoprotein, the N glycoprotein, or both the M and N glycoproteins
- In this case, the expected Mendelian genotypic ratio of 1:2:1 is observed, showing that codominance does not violate the expectations of Mendel’s laws.
Explain the phenomenon of multiple alleles.
- Many genes have more than two alleles (multiple alleles).
- Any individual can carry only two alleles of a gene, but members of a population can carry many different alleles of a gene.
EXAMPLE
- In humans, the gene for ABO blood types is a gene with more than two alleles; in this case, the gene has three alleles.
- Such genes are said to have multiple alleles.
- Your ABO blood type is determined by genetically encoded molecules (called antigens) present on the surface of your red blood cells.
- These molecules are an identity tag recognized by the body’s immune system.
- There is one gene (I) for the ABO blood types, and it has three alleles, IA, IB, and i. The IA and IB alleles control the formation of slightly different forms of the antigen.
- If you are homozygous for the A allele (IAIA), you carry the A antigen on cells and have blood type A.
- If you are homozygous for the B allele (IBIB), you carry the B antigen and are type B.
- The third allele does not make any antigen, and individuals homozygous for this allele carry no encoded antigen on their cells.
- The allele for the O blood type is recessive to both the A and B alleles. Because there are three alleles, there are six possible genotypes, including homozygotes and heterozygotes.
Explain the phenomenon of epistasis.
- Genes can interact to produce phenotypes.
- Soon after Mendel’s work was rediscovered, it became clear that some traits are controlled by the interaction of two or more genes.
- This interaction is not necessarily direct; rather, the cellular function of several gene products may contribute to the development of a common phenotype.
- One of the best examples of gene interaction is a phenomenon called epistasis – the interaction of two or more non-allelic genes to control a single phenotype.
- In epistasis, the action of one gene masks or prevents the expression of another gene.
EXAMPLE:
- An example of epistasis in humans can be seen when referring to the genetic basis for the ABO blood types.
- In a rare condition called the Bombay phenotype (named for the city in which it was discovered),a mutation in an unrelated gene prevents phenotypic expression of the A and B phenotypes.
- Individuals homozygous for a recessive allele h are blocked from adding the A or B antigen to the surface of their cells, making them phenotypically blood type O, even though genotypically they carry IA or IB alleles.
- In this case, being homozygous for the h allele (hh) prevents phenotypic expression of the IA or IB alleles and is a case of epistatic gene interaction.
Pedigrees use a standardized set of symbols. Identify and explain.
- In pedigrees, squares represent males and circles represent females.
- Someone with the phenotype in question is represented by a filled-in (darker) symbol.
- Heterozygotes, when identifiable, are indicated by a shaded dot inside a symbol or a half-filled symbol.
- If the sex of a person is unknown, a diamond is used.
- If there is doubt that a family member had the trait in question, that is indicated by a question mark above the symbol.
- Relationships between individuals in a pedigree are shown as a series of lines.
I. Parents are connected by a horizontal line
II. A vertical line leads to their off spring.
III. If the parents are closely related (such as first cousins), they are connected by a double line.
IV. The off spring are connected by a horizontal sibship line and listed in birth order from left to right along the sibship line
Explain the numbering system in pedigree construction.
Each generation is identified by a Roman numeral (I, II, III, and so on) and each individual within a generation is identified by an Arabic number (1,2,3, and so on).
What is a proband?
Proband: first affected family member who seeks medical attention for a genetic disorder
