Wk 13: An Interesting Proposal LO’s
Good Reference: http://ghr.nlm.nih.gov/handbook
“Genetics Home Reference” – your guide to understanding
genetic conditions”.
Mitosis Meiosis and Mendelian Inheritance
1. Review meiosis and how it differs from mitosis (1.03)
MITOSIS:
 a non-reductive cell division – each resultant daughter cell will have the same amount
of DNA as parent cell
 daughter cells are genetically identical to each other and to the parent
 single nuclear and cytoplasmic division
 occurs in SOMATIC cells – new cells (with identical DNA) for growth / repair.
 no exchange of genes
STAGES OF CELL DIVISION (MITOSIS)
 Interphase


Mitosis
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis
MEIOSIS:
 results in the production of gametes – haploid cells: in humans n= 23
 two nuclear divisions (and cytoplasmic)
 up to four daughter cells are formed
 daughter cells are not genetically identical to parent
 occurs in GAMETES (sex cells) – for reproduction
 genetic exchange – “crossing over” can occur – genetic variability achieved.
STAGES OF MEIOSIS
 Interphase
 Meiosis 1
Prophase 1
Metaphase 1
Anaphase 1
Telophase 1
 Meiosis 2
Prophase 2
Metaphase 2
Anaphase 2
Telophase 2
2. Define autosomal recessive inheritance
Autosomal recessive inheritance:
Refers to the pattern of inheritance of a condition
directly or indirectly due to a recessive faulty gene copy
located on an autosome.
Autosome:
Any of the numbered chromosomes, as opposed to the sex chromosomes.
Recessive:
Of, or pertaining to, a gene (or allele) whose phenotypic expression is masked
by a dominant gene (or allele).
3. Explain dominant and recessive mutations at the molecular level.
Mutations:
Anomalies in nucleic acids, chromatin or genomes can result in disease. These anomalies can
result in quantitative / qualitative differences in genetic material.
Different types of mutations.
Point mutations:
A mutation involving a change in a single base pair, or a deletion of a few base pairs.
Generally affects the function of a single gene .
 Missense mutation,
which results in a protein in which one amino acid is
substituted for another
 Nonsense mutation, in which a stop codon replaces an amino acid codon, leading to
premature termination of translation
 Frameshift mutation, which causes a change in the reading frame, leading to
introduction of unrelated amino acids into the protein, generally followed by a
stop codon
Small deletions have effects similar to those of frameshift mutations, although one third of
these will be in-frame and result in removal of a small number of contiguous amino acids.
See in-frame / out of frame form lecture (Wk12 “Clinical genetics”)
Chromosomal mutations (or abnormalities):
Involves large-scale changes in chromosome structure and can affect the functioning of
numerous genes, resulting in major phenotypic consequences. Such can involve deletion or
insertion of several contiguous genes, inversion of genes on a chromosome, or the exchange
of large segments of DNA between nonhomologous chromosomes
In many cases, the recessive allele is nonfunctional. Though a heterozygote may produce
50% of the functional protein compared to a dominant homozygote, this is sufficient to
produce the dominant trait.
4. Explain how Uniparental Disomy may occur.
Uniparental Disomy: (UPD)
Occurs when an individual inherits two copies of a chromosome pair from one parent and no
copy from the other parent. Under normal circumstances a baby inherits one copy of a gene
from the father and the other from the mother. Can be maternal or paternal. UPD can occur as
a random event during the formation of egg or sperm cells (non-disjunction at meiosis 1) or
may happen in early foetal development.
In many cases, UPD likely has no effect on health or development. Because most genes are
not imprinted, it doesn’t matter if a person inherits both copies from one parent instead of one
copy from each parent. In some cases, however, it does make a difference whether a gene is
inherited from a person’s mother or father. A person with UPD may lack any active copies of
essential genes that undergo genomic imprinting. This loss of gene function can lead to
delayed development, mental retardation, or other medical problems.
So:
UPD relates to issue of Genomic Imprinting. ie:
People inherit two copies of their genes—one from their mother and one from their
father. Usually both copies of each gene are active, or “turned on,” in cells. In some
cases, however, only one of the two copies is normally turned on. Which copy is
active depends on the parent of origin: some genes are normally active only when
they are inherited from a person’s father; others are active only when inherited from a
person’s mother. This phenomenon is known as genomic imprinting.
See more at: http://ghr.nlm.nih.gov/handbook/inheritance/updimprinting
Several genetic disorders can result from UPD or a disruption of normal genomic imprinting.
The most well-known conditions include Prader-Willi syndrome, which is characterized by
uncontrolled eating and obesity, and Angelman syndrome, which causes mental retardation
and impaired speech. Both of these disorders can be caused by UPD or other errors in
imprinting involving genes on the long arm of chromosome 15. Other conditions, such as
Beckwith-Wiedemann syndrome (a disorder characterized by accelerated growth and an
increased risk of cancerous tumors), are associated with abnormalities of imprinted genes on
the short arm of chromosome 11.
5. Define linkage and explain how mapping can be deduced from linkage
analysis.
Linkage:
The tendency for genes or segments of DNA closely positioned along a chromosome
to segregate together at meiosis and therefore be inherited together. - (University of
Washington and the National Center for Biotechnology Information)
Linkage is the close association of genes or other DNA sequences on the same
chromosome. The closer two genes are to each other on the chromosome, the greater
the probability that they will be inherited together. - (National Human Genome
Research Institute)
Linkage Analysis:
A gene-hunting technique that traces patterns of heredity in large, high-risk families,
in an attempt to locate a disease-causing gene mutation by identifying traits that are
co-inherited with it.
Gene Mapping:
Gene mapping is the process of establishing the locations of genes on the
chromosomes. Early gene maps used linkage analysis. The closer two genes are to
each other on the chromosome, the more likely it is that they will be inherited
together. By following inheritance patterns, the relative positions of genes can be
determined. More recently, scientists have used recombinant DNA (rDNA) techniques to
establish the actual physical locations of genes on the chromosomes.