unit 6a: mendelian genetics & chromosomal disorders
TRANSCRIPT
Gregor Mendel (mid 1800's) Mendel's work was done before the molecular basis
of chromosomal inheritance (i.e. meiosis and mitosis) was known.
His work formed the foundation from which subsequent work showed that genes existed on chromosomes and were indeed the inherited material passed on from generation to generation.
Mendel worked with pea plants for several reasons: 7 unique traits, most of which were “either/or” traits
(purple or white, wrinkled or smooth, etc) Closed flowers (prevented accidental pollination)
Character – a heritable feature (e.g. flower height) Trait – the variant for a particular character (e.g.
tall or short) So….
True-breeding – All offspring of a given plant are the same as the parent plant Either homozygous dominant (YY) or homozygous recessive (yy)
Hybridization – crossing (mating) of true-breeding varieties P generation – parental generation F1 generation – first generation F2 generation – second generation
Mendel's hypothesis included the following:
1. Alternate versions of genes (i.e. different alleles) account for differences in inherited characters
Gene for flower color is either purple or white
3. If the two alleles at a locus differ, one is dominant and one is recessive:
Dominant allele – determines organism's appearance
Recessive allele – no noticeable effect on organism's appearance
Law of Segregation Two alleles for a heritable character separate
(segregate) during gamete formation Thus egg or sperm (gametes) get only one copy
Law of Independent Assortment
Each pair of alleles of a given trait sorts itself independently of all other alleles of other traits Occurs during metaphase I (homologous pairs of each
chromosome line up) and metaphase II (sister chromatids of each chromosome separate) of meiosis
Homozygous – when the two alleles of a given trait are identical (e.g. PP or pp)
Heterozygous – when the two alleles of a given trait/gene are not identical (e.g. Pp)
Phenotype – physical trait; what you see (e.g. purple flowers)
Genotype – genetic makeup (e.g. PP or Pp) Example:
Pheno: purple, purple, white Geno: PP, Pp, pp
Punnett Squares
Monohybrid cross (one gene being looked at) PP (purple) x pp (white) (cross to F1 then cross F1 to F2) Phenotypic ratio; genotypic ratio
Dihybrid cross (two genes being looked at) YYRR (yellow round) x yyrr (green wrinkled) (cross to F1 then cross F1 to F2)
Types of Inheritence
1. Complete Dominance In the presence of at least one dominant allele,
the dominant phenotype will be expressed Ex: Pea plant flower color
PP – purple Pp – purple pp - white
2. Codominance An equal expression of both
(different) alleles results in a mixed phenotype
Examples: Blood type AB (both A antigens
and B antigens are expressed on blood cells)
Roan horses (both hair colors are present in equal numbers)
Non-Mendelian Types of Inheritance
3. Incomplete Dominance Phenotype is a blended version
of the two alleles Examples:
Snapdragon flowers: red (RR) x white (rr) yield all pink (Rr) flowers in F1 generation
Tay-Sachs disease: 2 copies of allele = death at early
age 1 copy of allele = brain cells produce
only ½ the enzyme in it's proper form (other ½ is mutated form)
4. Multiple Alleles A particular gene can have multiple (more than
two) but each individual only inherits two (one from mom and one from dad)
Example: Blood type (A, B, AB, O)
5. Sex-linked traits A gene located on either sex
chromosome is called a sex-linked gene (X in humans) Sex-linked gene (on X chromosome) Linked genes (genes that tend to be
inherited together on the same chromosome due to their close proximity)
Examples: Color blindness Hemophilia
6. Sex-limited traits Autosomal gene is present in both sexes but
expression depends on sex of individual (it’s dominant in one sex but recessive in the other)
Example: Baldness in males:
Man with one copy of gene will be bald Female needs two copies of gene to be bald
Milk production in females Man with one copy does not lactate Female with one copy lactates
5. Polygenic inheritance Many traits are the product of multiple genes and
their environment Examples:
Skin color, hair color Many genetic disorders (e.g. autism, cancer)
Extranuclear inheritance Some genes are passed from parent to offspring
without being part of nuclear chromatin Mitochondria (and chloroplasts in plants) are randomly
assorted into gametes and daughter cells In animals, mitochondrial traits are maternally inherited
Example: Leaf color in four o'clock plants Human mitochondrial disorders
Sex Chromosomes In humans, X and Y are the two
sex chromosomes In females (XX), one X is
inactivated in each cell (randomly) In males (XY), the X from mom is
always active X chromosome contains majority
of genetic information on sex chromosomes; Y chromosome is much smaller with only 70’ish genes
Gene linkage Genes adjacent (or close) on the
same chromosome tend to move as a unit; these genes are often termed “linked genes” Probability that they will segregate
as a unit is a function of distance between them
Mendel's laws of segregation and independent assortment only apply to genes on different chromosomes! Linked genes do not apply.
Gene Mapping based on recombination frequencies
Given the following table, construct a simple recombination map for the location of genes on a particular chromosome:
P and L – 30%
L and X – 5%
X and P – 35%
M and P – 10%
X and M – 45%
Chi-squared Test
Statistical test used to compare observed data with expected data to see if the null hypothesis (expected data) is within an acceptable range.
Mendel's work (circa 1850) showed existence of “hereditary factors”
Subsequent work showed these “factors” (i.e. genes) are located on chromosomes which are passed along from cell to cell via: Mitosis – occurs in somatic cells; results in 2 identical
diploid daughter cells Meiosis – occurs in germ cells; results in 4 non-
identical haploid daughter cells
Mutations• Mutations can arise from direct damage to DNA
OR from mistakes during meiosis
• Mutations can be:
Harmful Beneficial Neutral
A. Mutations directly to DNA
1. Mutation(s) during replication of DNA (S phase of cell cycle)
2. Environmental mutations carcinogens and/or toxins in environment modify bases on DNA strand
*In all cases, mutation will be passed on to all subsequent cells (unless mutation is
lethal)*
B. Mutations involving changes in chromosomes
1. Abnormal chromosomal number
Results from nondisjunction (members of a pair of homologous chromosomes do not move apart properly during meiosis II)
Aneuploidy – abnormal number of chromosomes Monosomic – only one copy Trisomic – three copies
Examples Trisomy 21 (aka Down's
Syndrome) Klinefelter Syndrome (XXY)
Male sex organs are present but small; male is sterile
Breast enlargement and other female body characteristics are often present
Turner's Syndrome (aka Monosomy X) Females are sterile; if given
estrogen replacement therapy, secondary sex characteristics will develop
2. Alterations in chromosome structure Deletion – chromosomal fragment is lost Duplication – chromosomal fragment is
duplicated (in tandem or in reverse) Inversion – part of chromosome breaks, inverts
180, and reinserts itself into same place on chromosome
Translocation – part of chromosome breaks apart and re-inserts into another part of chromosome or another chromosome entirely