Lecture 8

Effect of duplication
Duplication can be homozygous or heterozygous
Heterozygous - Lead to problems in chromosome pairing during prophase I of meiosis, chromosomes twist
and loop for correct pairing
Leads to phenotypic effects
Eg. Color blindness
Unbalanced gene dosage
Extra copies of gene increase the gene dosage leading to disruption of cell function and development

Deletions
Normal chromosome loops out during pairing in meiosis
Loss of essential genes, embryonic lethal
Imbalance in the gene dose, reduced gene dose, pseudodominance, haploinsufficient
Eg. Cri-du-chat syndrome
High pitched cat like cry of infants, small head, widely faced eyes, round face, intellectual disability
Due to deletion in short arm of chromosomes 5

Inversions
Chromosome segment is turned 180 degrees, no gene is gained or lost
Causes problems during pairing in Meiosis
Genes can lose their regulatory sequences, can displace genes from heterochromatin to euchromatin regions
In meiosis, inversions leads to reduced recombinations and production of non-viable gametes
Paracentric inversions: do not include the centromeres, result in gametes missing genes and non-viable
Pericentric inversions: includes centromere-result in nonviable gametes due to less or more number of genes

Translocations:
Movement of genetic material between non-homologous chromosomes
Non-reciprocal translocation: movement of genetic material without any reciprocal exchange
Reciprocal translocation: Two-way exchange between the chromosomes
Results in:
Loss of gene regulation in the new location

1
Disrupt gene regulation in the linkage site

Robertsonian translocation: Long arm of two acentric chromosomes joined to a common centromere generating
metacentric chromosomes: one with two long arms and one with two short arms
Short chromosome is lost in mitosis and meiosis because of small mass

During meiosis pairing and crossing over, abnormal pairing happens and based on segregation non-viable
gametes can result

Copy number variations:

DNA duplications and deletions detected by microarray, detected several copy number variations
Submicroscopic deletions and duplications are common and produce no phenotypic effect
But implicated in unexplained intellectual disability, osteoporosis, autism, schizophrenia, etc

Lecture 9
Aneuploidy
Increase or decrease in number of chromosomes
Arises due to loss of centromere and does not become incorporated during cell division
Small chromosome lost due to Robertsonian translocation
Chromosome nondisjunction during mitosis or meiosis

Aneuploidy types:
Nullisomy: Loss of both homologous chromosomes, 44

2
Monosomy: Loss of single homologous chromosomes, 45
Trisomy: Gain of a single chromosome, 47
Tetrasomy: Gain of two homologous chromosomes: 48
Double trisomic: 2n+1+1
Double monosomic: 2n-1-1

Aneuploid is mostly lethal: due to abnormal gene dosage

Due to inactivation, aneuploidy in X and Y chromosomes are common
30% of all zygotes formed in humans have aneuploidy and aborted. Only 2% of fetus with chromosome
abnormalities survive
PLK4 gene variants results in favoring aneuploidy

Turner Syndrome
Single X chromosome is present, can also be mosaic with XX and XO. Sterile with normal intelligence. No
embryos missing both X survive

Klinefelter Syndrome:
Have one or more Y and multiple X chromosomes
Commonly XXY, but also XXXY, XXXXY, XXYY
Sterile but have normal intelligence

Triple X syndrome: have XXX, females

Few are sterile but most are fertile, percentage of intellectual disability is higher

XYY males: no distinctive physical charactersitics except several inches taller than average
Normal intelligence but learning difficulties

XX males: A small part of Y chromosomes is attached to another chromosome, the genes are expressed to
develop male charactersitics. SRY gene is present in these individuals
XY females: SRY is absent in these females

But other X-linked, Y-linked and autosomal genes have fertility and development effects

3
Down syndrome: Trisomy 21-Primary down syndrome
Non disjunction in egg formation

Familial D own syndrome: Due to Robersonian translocation, Chr 21 and Chr 14 exchange parts and extra
Chr21 part remaining
Intellectual disability and distinct facial features

Edward syndrome: Trisomy 18: severe intellectual disability, deformed feet, heart problems, etc, do not survive
beyond a year after birth

Patau Syndrome: Trisomy 13

Severe intellectual disability, small head, die within a month

Uniparental disomy: originate from trisomies

Cystic fibrosis: a small portion received the two copies of chr 7 from a heterozygous parent

Genetic mosaicism or chimeras

Patches of cells with chromosome abnormality

Turners syndrome: few are 45 (X) and 46 (XX)

Case study: most RBCs were O type and some were A type
Due to nondisjunction in some cells, exchange between twins, etc

Lecture 10
Non dis-junction in meiosis I and Meiosis II

4
5
Hereditary: Mendelian genetics
Terminologies to know:
Gene
Alleles
Locus
Genotype
Phenotype
Heterozygous
Homozygous
Trait
Dominant
Recessive
Genetics started with Gregor Johann Mendel, an Augustinian Monk at now the Czech republic

Experiments on Pea plants- Pisum sativum

Experiments on monohybrid cross: Differed in single characteristic
P – Parental
F1-First Filial or offspring
F2-Second filial generation
Mendel counted 5474 round seeds and 1850 wrinkled seeds in F2

Lecture 11
Mendel’s first law: Law of Dominance
1. Each organism has two alleles for a trait
2. Only the dominant trait is expressed in the heterozygous condition
Second law: Law of segregation
3. Alleles separate when gametes are formed – Anaphase I
4. Alleles separate in equal proportions – Anaphase I
Third law: Law of independent assortment
Alleles at different loci separate independently – Anaphase I

Characteristics analyzed by Mendel:

6
 1. Seed color: Yellow or green
2. Seed shape: round or wrinkled
3. Flower color: purple or white
4. Pod color: Green or Yellow
5. Pod shape: Inflated or constricted
6. Flow position: Axial (along stem) or terminal (at the tip of stem)
7. Stem length: Tall or short

Test cross
To detect the genotype of an organism expressing dominant phenotype by crossing with homozygous recessive
individual
Back cross:
F1 generation with one of the parents

7
Lecture 12

Medical genetics
When studying rare disorders, 6 general patterns of inheritance are observed:
• Autosomal recessive e.g. cystic fibrosis
• The disease occurs in 1 in 2,500 to 3,500 white newborns. Cystic fibrosis is less common in other ethnic
groups, affecting about 1 in 17,000 African Americans and 1 in 31,000 Asian Americans.

8
• CFTR gene provides instructions for making a channel that transports negatively charged particles called
chloride ions into and out of cells

•
• Autosomal dominant e.g. Huntington’s disease nervous disorder affecting muscle movements
The HTT mutation that causes Huntington disease involves a DNA segment known as a CAG trinucleotide
repeat. In people with Huntington disease, the CAG segment is repeated 36 to more than 120 times. An
increase in the size of the CAG segment leads to the production of an abnormally long version of the
huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and
accumulate in neurons, disrupting the normal functions of these cells.
•
• X-linked recessive e.g. Haemophilia

• X-linked dominant e.g. fragile X syndrome - learning disabilities and cognitive impairment

FMR1 gene has more CGG repeats and so the neuronal synapses are affected
9
•
•

• Red eyes, white eyes in drosophila

•
• Codominant
• ABO blood grouping

• Mitochondrial E.g. Leber's hereditary optic neuropathy (LHON)

10
•

11