MOLECULAR AND CELL BIOLOGY II (MCBN 172)
Chromosomes, Mapping, and the Meiosis Inheritance
Connection (Chapter 13, Study unit 2)
Lecturer: Miss Sinenhlanhla Mthembu
[email protected]https://www.linkedin.com/in/sinenhlanhla-x-h-mthembu/
Genetic recombination exchanges alleles on homologues
-According to Mendeley, all genetic traits located in
chromosomes assort independently during meiosis.
Is this entirely true?
Linkage and Recombination
Linkage on Chromosomes 1
Genes located on the same chromosome are said
to be linked, as they are physically connected and
tend to be inherited together during meiosis. 2 Recombination Process
During meiosis, genetic material can be shuffled
through a process called recombination, where
Crossing Over and Chiasmata homologous chromosomes exchange sections,
Recombination is facilitated by the formation 3 creating new allele combinations.
of crossover points called chiasmata, where
the homologous chromosomes physically
connect and exchange genetic material.
Constructing Genetic Maps
Chromosome Recombination Linkage Analysis Genetic Map
Mapping Frequency Construction
Statistical
Genetic mapping The frequency of Constructing a
techniques like
involves locating genetic genetic map
linkage analysis
genes on specific recombination involves ordering
are used to
chromosomes and between two loci is genes along
determine the
determining their used to estimate chromosomes and
relative positions
relative positions. the distance determining the
of genes based on
between them on recombination distances between
the chromosome. frequencies. them.
Genetic mapping
-Recombination is the basis for genetic maps
-The ability to map the location of genes on chromosomes using data from genetic crosses is one of
the most powerful tools of genetics.
-The frequency of recombination is defined as the number of recombinant progeny divided by
total progeny. This value is converted to a percentage, and each 1% of recombination represents
one map unit.
Recombinant frequency (RF) = Recombinant progeny x 100
Total progeny
- This unit has been named the centimorgan (cM) for T. H. Morgan, although it is also called simply a map
unit (m.u.) as well.
Constructing maps
-Two-point cross to map genes. Flies homozygous for long wings (vg+) and gray bodies (b+) are crossed to flies
homozygous for vestigial wings (vg) and black bodies (b). Both vestigial wings and black body are recessive to
the normal (wild-type) long wings and gray body. The F1 progeny are then testcrossed to homozygous vestigial
black to produce the progeny for mapping.
The sum of the recombinant
progeny is divided by the total
progeny to produce the
recombination frequency. In this
case, the recombination frequency
is 92 + 88 divided by 1000, or 0.18.
Converting this to a percentage
yields 18 cM as the map distance
between these two loci.
Understanding Two Crossovers
-When homologous chromosomes undergo a single crossover between two loci, it leads to the exchange
of genetic material between them, resulting in recombinant chromosomes (chromosomes with a new
combination of alleles compared to the parents).
-However, if there are two crossovers between the same two loci, the overall effect can be different
•First crossover: The alleles from the two homologous chromosomes are exchanged, creating
recombinant chromosomes.
•Second crossover: The second crossover essentially undoes the first one by swapping the same
segments of genetic material again. As a result, the alleles on the chromosomes are restored to the
original parental combinations.
-In this case, odd numbers of crossovers (1, 3, 5) produce recombinant gametes, and no crossover or even
numbers of cross overs (0, 2, 4) produce parental gametes.
Understanding three-point crosses
•A three-point cross involves analyzing the recombination
between three genes to determine their order on the
chromosome.
•Parental types, single crossover recombinant types,
and double crossover recombinant types are observed.
•By comparing the frequency of these types, especially the
double crossovers, the order of genes can be deduced, and
map distances between genes can be calculated.
•This method is an essential tool in genetic mapping and
helps scientists understand the physical arrangement of
genes on chromosomes
Genetic maps can be constructed for the human genome
-Human genes can be mapped, but the data must be derived from historical pedigrees, such as those of the
royal families of Europe.
-The principle is the same—genetic distance is still proportional to recombination frequency—but the
analysis requires the use of complex statistics and summing data from many families.
The difficulty of mapping in humans
-Disease-Causing Alleles in Humans - Unlike nonhuman animals, where genetic markers can be associated with easily visible
traits, human disease-causing alleles don’t have obvious visible effects, which makes it
harder to track them in genetic maps.
- The Challenge of Low Marker Numbers - Back in the early 1980s, when scientists first started trying to map the human
genome, the number of genetic markers available for study was very low—only in
the hundreds
Anonymous markers
•Anonymous markers are genetic markers that don’t show visible traits but can be detected using molecular
techniques.
• They have allowed scientists to greatly increase the number of genetic markers available, from hundreds to
thousands, and helped create a much more detailed human genetic map.
• Due to the ability to automate these techniques, geneticists now have the tools to map human genes with
unprecedented accuracy and efficiency, something that would have been difficult or impossible just a few decades
ago.
Single-nucleotide polymorphisms (SNPs)
• SNPs are the most common genetic variations between individuals and involve a difference in a single base pair in
the DNA sequence.
• With around 10 million SNPs identified in the human genome, they have become a powerful tool for gene
mapping and studying complex traits (like diseases and behaviors).
• SNPs are also used in forensics, paternity testing, and can help guide personalized medicine by revealing
individual genetic differences related to disease risk and drug responses.
Selected human genetic disorders
Sickle cell anaemia
-Caused by a defect in the oxygen carrier molecule, that leads to
impaired oxygen delivery to tissues.
-The defective haemoglobin molecules stick to one another,
leading to stiff, rodlike structures
-Individuals homozygous for the sickle cell allele exhibit
intermittent illness and reduced life span
-Individuals heterozygous for the sickle cell allele are indistinguishable from normal individuals in a normal
oxygen environment
-Prevalent in people of African descent (up to 45% of the population is heterozygous for the trait)
-Heterozygosity confers a greater resistance to the blood-borne parasite that causes malaria
Nondisjunction
-The failure of homologues or sister chromatids to separate properly during meiosis
-Leads to the gain or loss of a chromosome (aneuploidy)
Nondisjunction of autosomes
-Humans who have lost even one copy of an autosome are called monosomics
-Humans who have gained an extra autosome are called trisomics
-13,15, 18, 21, and 22—can be present as three copies and still allow the individual to survive
-Extra chromosome 13, 15, or 18 causes severe developmental defects
-Individuals who have an extra copy of chromosome 21 or chromosome 22, usually survive to
adulthood
-Developmental defect produced by trisomy 21 is called Down syndrome
-Translocation Down syndrome —small portion of chromosome 21 containing the critical segment
has been added to another chromosome
Nondisjunction of sex chromosomes
-Individuals who gain or lose a sex chromosome do not generally experience the severe developmental
abnormalities caused by similar changes in autosomes.
X chromosome nondisjunction
1 functional X chromosome
Zygote develops into a female Female body
Maybe taller in stature but characteristics
normal in appearance
Develops into a sterile female of short stature,
Sex organs never fully mature during puberty
Y chromosome nondisjunction
-When YY gametes combine with X gametes, the XYY zygotes develop into fertile males of normal
appearance (Jacob syndrome)
Genomic imprinting
-Imprinting affects how certain genes are expressed based on which parent they come from
-Some genes from the father or mother are silenced, leading to the gene’s effect being dependent on
its parent of origin
-The basis for genomic imprinting is the expression of a gene depending on passage through maternal
or paternal germ lines
Some genes are inactivated in the paternal germ line and therefore are not expressed in the zygote
Other genes are inactivated in the maternal germ line, with the same result
zygote becomes haploid for an imprinted gene
Example of genomic imprinting
Prader–Willi syndrome (PWS) — characterised by respiratory distress, obesity,short stature, mild
intellectual disability, and obsessive–compulsive behaviour (paternal)
Angelman syndrome —characterized by developmental delay, severe intellectual disability, hyperactivity,
aggressive behaviour, and inappropriate laughter (maternal)
NB:The most common cause of both syndromes is a deletion of material on chromosome 15
Epigenetic Mechanisms in Imprinting
- DNA Methylation: A common epigenetic modification where a methyl group is added to the DNA,
often silencing the gene. In imprinting, one parent's gene copy may be methylated (silenced), while the
other parent's copy is not.
- - Histone Modifications: Proteins called histones help package DNA, and chemical changes to histones
can also affect gene expression. In imprinted genes, specific histone marks can make genes from one
parent inactive.
Genetic counseling
-Is aimed at identifying parents at risk for having children with genetic defects and of assessing the genetic state
of early embryos.
• Pedigree analysis
One way of assessing risks is through pedigree analysis, often employed as an aid in genetic counseling. By
analyzing a person’s pedigree, it is sometimes possible to estimate the likelihood that the person is a carrier for
certain disorders.
- Down syndrome
- Cystic fibrosis
What did you lean?
Genetic mapping
Workout the following genes and provide their location
in a chromosome.
B A D C
1 2 3 4
