Lecture 8 Heredity

Mendel and Patterns of Inheritance The tendency for traits to be passed from parent to offspring is called heredity Gregor Mendel (1822-1884) The first person to systematically study heredity Austrian monk who studied science and mathematics Worked with garden peas in his monastery

Mendel’s Experimental System Mendel chose the garden pea for several reasons Many distinctive varieties were available Small and easy to grow Short generation time and lots of offspring Both male and female reproductive organs are enclosed within the pea flower

Mendel’s Experimental Design Mendel selected seven characteristics to study, each of which had two distinguishable traits He let each variety self-fertilize for many generations to ensure it was true-breeding He crossed individuals from two different varieties that differ in only one trait P (parental) generation = Pure bred lines F1 (First filial) generation = Offspring of cross-fertilization of parentals F2 (Second filial) generation = Offspring of self-fertilization of F1 plants

What Mendel Observed For all seven pairs of contrasting traits studied, Mendel observed the same results The F1 generation showed only one of the two parental traits He called it the dominant trait The recessive trait was not expressed Mendel let the F2 plants self-fertilize for another generation The F2 generation showed an ~ 3:1 ratio of the dominant:recessive parental traits He concluded from the results that the 3:1 ratio is a disguised 1:2:1 ratio

Mendel’s Theory Mendel proposed a simple set of hypotheses Parents do not transmit traits directly to their offspring They do so via factors (now termed genes) Each parent contains two copies of the factor governing each trait If the two copies are the same, the individual is called homozygous If the two copies are different, the individual is called heterozygous Alternative forms of a factor lead to different traits Alternative forms are called alleles The appearance of an individual is its phenotype The genetic composition of an individual is its genotype The two alleles that an individual possesses do not affect each other The presence of an allele does not ensure that its trait will be expressed in the individual

Translating Mendel’s Results to Chromosomes Each trait is determined by the inheritance of two alleles: one maternal and one paternal These alleles, present on chromosomes, are distributed to gametes during meiosis Genes on homologous chromosomes

Punnett Squares Consider Mendel’s cross of purple-flowered with white-flowered pea plants P (dominant) allele  Purple flowers p (recessive) allele  White flowers Using these conventions, the above cross can be symbolized as PP X pp A Punnett square is a grid structure that enables the calculation of the results of simple genetic crosses Gametes p P Possible gametes are listed along two opposite sides PP Pp Genotypes of potential offspring are represented by the cells in the square The frequency of these genotypes in the offspring is expressed by a probability Pp pp PLAY Punnett Squares

Mendel’s Flower Color as Punnett Square Probability is 25% Probability is 100% 50% 50% 25%

The Testcross A genetic procedure devised by Mendel to determine an individual’s actual genetic composition A purple-flowered plant can be homozygous (PP) or heterozygous (Pp) One cannot tell by simply looking at the phenotype One can tell from the results of a cross between the test plant and a homozygous recessive plant

Mendel’s Laws Mendel’s theory of heredity is one of the most important theories in the history of science It has been so well supported by experimental results that his major proposals are considered “laws” Mendel’s first law, or law of segregation The two alleles of a gene separate when forming gametes, and gametes combine randomly in forming offspring Mendel’s second law, or law of independent assortment Alleles of genes located on different chromosomes are inherited independently of one another

Crossover Homologous chromosomes synapse in meiosis I One chromosome segment exchanges positions with its homologous counterpart Genetic information is exchanged between homologous chromosomes Two recombinant chromosomes are formed

Crossover

Random Fertilization A single egg is fertilized by a single sperm in a random manner Considering independent assortment and random fertilization, an offspring represents one out of 72 trillion (8.5 million  8.5 million) zygote possibilities

How Genes Influence Traits Genes specify the amino acid sequence of proteins The amino acid sequence determines the shape and activity of proteins Proteins determine in large measure what the body looks like and how it functions Mutations in a gene result in alleles This ultimately leads to a change in the amino acid sequence and, hence, activity of the protein Natural selection may favor one allele over another

Dominant-Recessive Inheritance Reflects the interaction of dominant and recessive alleles Punnett square – diagram used to predict the probability of having a certain type of offspring with a particular genotype and phenotype Example: probability of different offspring from mating two heterozygous parents T = tongue roller and t = cannot roll tongue Examples of dominant disorders: achondroplasia (type of dwarfism) and Huntington’s disease Examples of recessive conditions: albinism, cystic fibrosis, and Tay-Sachs disease Carriers – heterozygotes who do not express a trait but can pass it on to their offspring

Some Traits Don’t Show Mendelian Inheritance Mendelian segregation of alleles can be disguised by a variety of factors Incomplete Dominance Codominance Continuous (polygenic) variation Sex Linked Effects Pleiotropic Effects Environmental Effects Extrachromosomal Inheritance Aneuploidy

Incomplete Dominance SS = normal Hb is made Heterozygous individuals have a phenotype intermediate between homozygous dominant and homozygous recessive Sickling gene is a human example when aberrant hemoglobin (Hb) is made from the recessive allele (s) SS = normal Hb is made Ss = sickle-cell trait (both aberrant and normal Hb is made) ss = sickle-cell anemia (only aberrant Hb is made) Normal red blood cell Sickled red blood cell

Codominance & Polygenic Inheritance Polygenic genes exhibit more than two alternate alleles ABO blood grouping is an example Three alleles (IA, IB, i) determine the ABO blood type in humans IA and IB are codominant (both are expressed if present), and i is recessive Possible alleles from female IA or IB i IAIA IAIB IAi IA IB i or Possible alleles from male IBi IAIB IBIB IAi IBi ii A AB B O Blood types

Continuous (Polygenic) Inheritance Example: Skin Color Examples: skin color, eye color, and height Depends on several different gene pairs at different loci acting in tandem Results in continuous phenotypic variation between two extremes Alleles for dark skin (ABC) are incompletely dominant over those for light skin (abc) The first generation offspring each have three “units” of darkness (intermediate pigmentation) The second generation offspring have a wide variation in possible pigmentations

Sex-Linked Inheritance Inherited traits determined by genes on the sex chromosomes X chromosomes bear over 2500 genes; Y chromosomes carry about 15 genes X-linked genes are: Found only on the X chromosome Typically passed from mothers to sons Never masked or damped in males since there is no Y counterpart

Pleiotropic Effects The same allele can have different effects depending upon the source parent Deletions in chromosome 15 result in: Prader-Willi syndrome if inherited from the father Angelman syndrome if inherited from the mother During gametogenesis, certain genes are methylated and tagged as either maternal or paternal Developing embryos “read” these tags and express one version or the other

Environmental Influence on Gene Expression Phenocopies – environmentally produced phenotypes that mimic mutations Environmental factors can influence genetic expression after birth Poor nutrition can effect brain growth, body development, and height Childhood hormonal deficits can lead to abnormal skeletal growth

Extrachromosomal (Mitochondrial) Inheritance Some genes are in the mitochondria All mitochondrial genes are transmitted by the mother Unusual muscle disorders and neurological problems have been linked to these genes

Human Chromosomes & Aneuploidy Human somatic cells have 23 pairs of chromosomes 22 pairs of autosomes 1 pair of sex chromosomes XX in females XY in males Failure of chromosomes to separate correctly in meiosis I or II is termed non-disjunction This leads to an abnormal number of chromosomes, or aneuploidy

Aneuploidy Humans with one less autosome are called monosomics These do not survive development Humans with one extra autosome are called trisomics The vast majority do not survive Trisomy for only a few chromosomes is compatible with survival However, there are severe developmental defects Down Syndrome is caused by trisomy 21

Nondisjunction Involving Sex Chromosomes Aneuploidies of sex chromosomes have less serious consequences than those of autosomes However, they can lead to sterility Nondisjunction of the Y chromosome Yields YY gametes and ultimately XYY zygotes Frequency of XYY is 1 in 1,000 males In general, these are phenotypically normal

Genetic Screening, Counseling, and Therapy Newborn infants are screened for a number of genetic disorders: congenital hip dysplasia, imperforate anus, and PKU Genetic screening alerts new parents that treatment may be necessary for the well-being of their infant Example: a woman pregnant for the first time at age 35 may want to know if her baby has trisomy-21 (Down syndrome) Ultrasound Used to locate the fetus during amniocentesis Used to examine the fetus for signs of major abnormalities Amniocentesis Usually performed in the fourth month of pregnancy

Carrier Recognition Identification of the heterozygote state for a given trait Two major avenues are used to identify carriers: pedigrees and blood tests Pedigrees trace a particular genetic trait through several generations; helps to predict the future Blood tests and DNA probes can detect the presence of unexpressed recessive genes Sickling, Tay-Sachs, and cystic fibrosis genes can be identified by such tests

Fetal Testing Is used when there is a known risk of a genetic disorder Amniocentesis – amniotic fluid is withdrawn after the 14th week and sloughed fetal cells are examined for genetic abnormalities Chorionic villi sampling (CVS) – chorionic villi are sampled and karyotyped for genetic abnormalities

Human Gene Therapy Genetic engineering has the potential to replace a defective gene Defective cells can be infected with a genetically engineered virus containing a functional gene The patient’s cells can be directly injected with “corrected” DNA