Lecture 1: Inheritance Patterns and Chromosomes
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Disease – abnormal condition of organism or part, especially as a
consequence of infection, inherent weakness, or environmental stress that
impairs normal physiological function.
Phenotype – Genotype + Environment
Genotype – Based on DNA sequence
Homologous Pair – In genetics, one allele from each parent for each
characteristic.
Homozygous – Purebred, same allele from both parents
Heterozygous – Different allele from each parent
Punnett’s Square – Square which shows the different ways in which to cross
gametes from the mother and the father, so that all of the possible zygotes
are shown.
Uniformity – Crossing of two homozygotes with different alleles yields
identical, heterozygous offspring.
Segregation – Each individual carries two genes for a characteristic, but the
zygote only gets one allele from the mother, and one allele from the father.
Independent Assortment – Members of different gene pairs segregate to
offspring independently of each other.
o How is the Law of Independent Assortment broken? Gene linkage.
Alkaptonuria – Autosomal Recessive Disorder. A mutation in position 3 on
the chart leads to deficiency of homogentistic acid oxidase, which causes the
disease
o
How many molecules per genome per cell? 23 molecules
How many base pairs in euchromatin? 3X10^9 bp
What percentage of the DNA sequence is conserved? 5%
How long is the DNA in the cell before coiling? 2m/cell
How many genes are there? 23,000 genes
To what accuracy is the genome sequenced? Why is this number important?
The genome is sequences to 99.99% accuracy. This is important because any
two unrelated individuals differ by .01%.
What is an Open Reading Frame? In mRNA, open reading frames code for
proteins.
Huntington’s Disease – Autosomal Dominant Disease where patients are
forgetful, and have jerky, grimacing movements.
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Marfan Syndrome – Autosomal Dominant Disease
Achondroplasia – Autosomal Dominant Disease
Osteogenesis Imperfecta – Autosomal Dominant Disease
Cystic Fibrosis – Autosomal Recessive Disease. Can present as
Pseusodominant in areas where it is more common. Infected patients have
severe chest infections and bulky stools. A sweat electrolyte test above 60
mM can confirm. Males with CF are infertile.
Sickle Cell Anemia – Autosomal Recessive
Bilateral Hearing Loss – Autosomal Recessive
Thalassaemia – Autosomal Recessive
Consanguinity – Increases the risk of a child with a recessive disease
Does limited population size imply consanguinity? No
Pseudodominant Pedigree – A recessive allele is so common in the
population that it would be possible for a homozygote to have affected
children with a heterozygous carrier frequently.
What are some examples of Pseudodominant Disorders? ABO, Blue Eyes,
Sickle Cell, Cystic Fibrosis.
Complementation – Both parents have the same recessive phenotype, but the
mutation is at a different locus. All children are heterozygous for both alleles
and are unaffected by the phenotype.
Locus Heterogeneity – Same phenotype in two different people that leads to
the same disease or recessive phenotype. Can lead to complementation in
children.
Duchenne Muscular Dystrophy – X-Linked Recessive Pedigree. Child uses
Gower’s Maneuvre to rise from the floor.
Obligate Carrier – In X-linked Recessive Disorders, if the son is affected with
the disease, the mother must be a carrier of the disease. Symbol is a circle
with a dot in the middle.
Blind or Impaired Vision (due to retinal changes) – Mitochondrial
Inheritance example.
Mitochondrial Inheritance – Mitochondrial DNA is only inherited from the
mother. Therefore, only mother can pass down recessive phenotypes in
mitochondrial inheritance.
Penetrance – The proportion of individuals with a mutation who exhibit the
phenotype.
Variable Expressivity – Different symptoms (or severity of symptoms) in
individuals with the same mutations
X-Linked Dominant – Most of the time, only females are affected because the
disease is male-lethal.
Mosaic – Composed of two different cell populations (one with mutation, one
without). It is a somatic mutation after fertilization. It can only be passed on
if in the parental germ line.
Polyploidy – Extra copies of the entire genome
o Triploidy – 3 genome copies
o Tetraploidy – 4 genome copies
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Aneuploidy – Extra copies of particular chromosomes.
o Monosomy, Trisomy, Tetrasomy = 1, 3, 4, copies of one particular
chromosome
o What are the 3 origins of trisomy?
 Normal (n) egg + 2 separate sperm, each (n) = 3n (66%)
 2n egg fertilized by one, normal sperm (n) = 3n (10%)
 Normal (n) egg + 2n sperm = 3n (24%)
o What is the origin of tetrasomy?
 Normal fertilization (n) egg + (n) sperm. But cell does not
divide after DNA duplication = 4n
o What is Trisomy 21?
 Down’s Syndrome. Can also happen because of Robertsonian
Translocation. Excess nuchal skin, epicanthic folds, upward
sloping palpebral fissues, single palmar crease, etc.
o What is Trisomy 13? Patau Syndrome. Cleft lip.
o What is Trisomy 18? Edward’s Syndrome. Large protruding back of
head.
Chromatids – Two sister chromatids are held together by cohesion proteins
to form the signature X shape of chromosomes during Prophase. Usually,
cohesion proteins are throughout the entire chromosome, but separase
removes all of the cohesion besides what is left at the centromere.
How often must recombination occur? At least once for each pair of
homologous chromosomes.
Meiosis I – Separates homologous chromosomes, still 2n.
Meiosis II – Separates sister chromatids, results in haploid gametes.
How many possible combinaions are there for 23 (human) chromosomes?
2^23
What are the stages of Oogenesis? 2n zygote (1)  2n oogonia (2)  2n
oogonia (2)  2n primary oocyte (2)  n secondary oocyte (2)  mature
(n) gamete + 4 polar bodies.
What are the stages of Spermatogensis? 2n zygotes (1)  2n spermatogonia
(2)  2n spermatogonia (2)  2n primary spermatocyte (2)  n secondary
spermatocyte (2)  4 mature sperm (n)
What are the steps for preparing a karyotype? Draw blood  Add
phytohaemagglutinin (stimulates cell division)  Culture for 3 days  Add
colchicine (to prevent spindle formation)  Cells arrest in Metaphase  Add
hypotonic saline (fixes cells)  Add to slide  Digest with Trypsin  Stain
with Giemsa  Analyze Spread
Metacentric Centromere – The centromere is in the middle. The P arm and
the Q arm are equal in length.
Submetacentric Centromere – The centromere is not directly in the middle.
The P arm is shorter than the Q arm.
Acrocentric Centromere – The P arm is only satellite DNA, and the Q arm is
normal.
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What is the trend of the human chromosomes? As you go from chromosome
1 to chromosome 23, the length is largest to smallest (21 is smaller than 22).
What is a misconception about the Y-Chromosome? It is classically defined
as acrocentric, but it isn’t because it has little/no satellite DNA.
What are the results of non-disjunction in Meiosis 1? Two trisomies, two
monosomies.
What are the results of non-disjunction in Meiosis 2? One trisomy, one
monosomy, two normal.
When does non-disjunction most often occur? Maternal Meiosis I.
Turner Syndrome – 45X. Short, puffy feet, excess nuchal skin, ovarian stroma
devoid of germ cells, infertility.
Klinefelter Syndrome – 47 XXY. Male with female secondary sex
characteristics (female pubic hair, breast development, hypogonadism).
Triple X Syndrome – 47XXX
47XXY – Tall stature
What is the formula for barr body number? One only X chromosome is
active. Barr bodies = n-1.
Reciprocal Translocations – sections of the arms translocate (does not
involve centromere) can result in normal gametes, balanced carriers, or
trisomy and monosomy.
Robertsonian Translocation – Exchange in short arms (Satellites) of satellite
DNA. Satellites are lost and there are two centromeres on one chromosome.
o Adjacent Meiosis – leads to unbalanced translocation
o Alternate Meiosis – leads to balanced translocation
Pericentric Inversion – Chromosome breaks on both sides of the centromere.
Can result in a ring chromosome.
Paracentric Inversation – Chromosome breaks on one side of the centromere
Wolf-Hirschhorn Syndome – 4p deletion.
Cri du Chat Syndrome – 5p deletion. Cat-like cry, mental deficiency.