SUMMARY MINOR GENOMICS RESEARCH
– FROM MOLECULE TO POPULATION
Elective minor year 3 Biomedical Sciences
Radboud University, Nijmegen
Made by: Georgia Graat
,Summary minor genomics part 1
Repetition genomics
Your phenotype and behavior are determined by your genetics and environment. Genetics is all the
information stored in your genes, fixated at birth. A human has 46 chromosomes with 3-4 billion
base pairs, consisting of the bases ACTG (or ACUG in RNA). There are 23 chromosome pairs, 22
autosomal and 1 sex pairs. These contain only 20.000 genes in total. This all together makes up the
DNA.
Gene = a distinct sequence of nucleotides forming part of a chromosome, the order of which
determines the order of amino acids in a polypeptide. A part of the genome that is inherited from a
parent and determines some characteristic in an individual; the real carriers of genetic information
Allele = one of two (or more) versions of a gene that
are found at the same place on a chromosome in the
gene itself and determines a specific trait. Two alleles
are inherited for each gene, one from each parent. It is
usually described as the specific nucleotide on that
locus, or as one capital/small letter when there are
two possibilities. The genotype is defined as the
collection of all the alleles within an individual, as well
as the combination of genes at a particular locus (place
on the genome/chromosome)
Haplotype = the combination of alleles as they occur
on a unique chromosome, which determines
homozygous/heterozygous forms for a specific gene. Can be determined for one or multiple loci
Hereditary = inheritable within the family/passed down from parents to children
De novo = completely new. A de novo mutation means no inheritance has taken place, and
somewhere during the growth of the infant and replication of DNA, a mutation has occurred
somatically. After, the new mutation could be passed on to offspring
Congenital = heritable (child is born with it)
Concordance = similarity in a characteristic/trait in twins
Heritability = measure of genetic contribution to the variation of a characteristic/trait. Meaning this
is the degree to which genes have an effect on the quantity of a phenotype in the population
Consanguinity = the relationship between two people who share a common ancestor
Genetic variation = the existence of differences in the genetic material of a population
Heteroplasmy = the presence of more than one type of genome (mitochondrial or normal DNA)
within a cell or individual, so multiple types of DNA with different alleles occur at the same time
Anticipation = disease is passed on in the family but manifests itself at an increasingly younger age
each generation
Penetrance = how often the abnormal phenotype is identified with an abnormal genotype, meaning
how often the gene defect leads to the symptoms of a disease. Incomplete or reduced penetrance is
similar to a certain chance of a disease; it is either expressed or not in a single individual
Made by: Georgia Graat
,Variable expression = the same gene defect results in a different variable clinical picture in different
individuals. Symptoms range from none to mild to severe and/or a difference in symptoms is
expressed. Causes are age, environmental influence, and the rest of the genome/genetic variants
Karyotyping = the technique of pairing and arranging the chromosomes, useful for detecting large
genetic errors
Mendelian inheritance of a certain trait means the offspring receives one gene with a certain allele
from both parents and thus has two. This determines homozygous/heterozygous for an individual as
well. Mitochondrial inheritance is always only from mother to child, as the mitochondria of the father
remain in the tail of the sperm cell. Multifactorial inheritance means genetics and environment both
play a role in the hereditary and expression of a disease/trait. The higher the prevalence of a disease,
the less likely inheritance is.
The smallest parts of DNA are a base (ACTG) and a sugar that
together form a nucleoside. When a phosphate group binds to
this, it becomes a nucleotide. Nucleotides together in a string
form a nucleic acid. With base pairing is meant that bases have
the possibility to form either 2 (between AT) or 3 (between CG)
hydrogen bonds. The nucleic acids forms strings to make DNA as a
double helix with two anti-parallel strains. When DNA binds
around histones, it becomes nucleosomes. These form to fibers,
then chromatin and eventually one chromosome. One
chromosome therefore normally exists of 1 double stranded DNA
strain.
Transcription is regulated by
the cell itself that determines
whether a gene is turned on or
off. Euchromatin has active
genes and heterochromatin
inactive. A gene is expressed or transcribed through an interplay
between proteins and DNA. First, the transcription factors bind to
the TATA-box, so the RNA-polymerase can bind to the promotor.
Co-activators then bind to the factors and determine the speed of
transcription by activating or repressing the polymerase.
The DNA contains the promotor where the transcription factors can bind. After that, everything from
the DNA gene is read (exons, introns, 5’ UTR and 3’ UTR) by RNA polymerase. DNA is always read
from the 3’ to the 5’ side at the template strand. Pre-mRNA is thus made from 5’ to 3’, but after
Made by: Georgia Graat
, splicing via spliceosomes the mature RNA is also read 5’ to 3’ for translation. This is to make the
protein 3’ to 5’ where it is in a more stable form. The pre-mRNA consists of introns and exons, and
both UTR parts. Mature RNA only consists of the exons and both UTR parts. The UTR is non-coding
and right behind the 5’ UTR in the first exon is the starting codon. Right before the 3’ UTR at the end
in the last exon is the stop codon. Alternative splicing is the case when one gene can result in many
different transcripts and proteins. This splicing happens when the spliceosomes leave out certain
exons from the mature RNA that are not encoded in a certain scenario and thus ‘’skipped’’.
DNA-synthesis is needed for every cell duplication and DNA
repair. This happens in the S-phase of the interphase. In humans,
this happens through semi-conservative replication where two
new helixes both consist of one original and one replica strand.
Replication starts at many origins at the same time where helicase
pulls the helix apart. It is always read 3’ to 5’ and thus made 5’ to
3’. DNA primase makes a primer consisting of RNA, essential for
DNA synthesis. DNA polymerase extends this primer towards the
3’ end, forming the leading strand. As the DNA polymerases are
bound together, this is more difficult for the lagging strand. To
resolve this, a primer is put a little upstream of the DNA, and DNA
polymerase makes a small Okazaki fragment 5’ to 3’ behind this. Another DNA polymerase turns the
RNA-primers into DNA and DNA ligase binds the Okazaki-fragments together. DNA polymerase has
proofreading and can delete a wrong nucleotide with exonuclease.
Mitosis happens in all cells of the body to renew. The 46 chromosomes with 46 chromatids/DNA
strands duplicate to make 46 chromosomes with 92 chromatids/DNA strands. All these duplicated
chromosomes form one line and the sister chromatids are pulled apart, making two cells with each
46 chromosomes with 46 chromatids.
Meiosis happens only in the germline cells and takes place a little differently. These have to be
haploid egg/sperm cells that only turn diploid after fertilization. Meiosis I starts with 46
chromosomes containing 92 chromatids/DNA strands. Each homologous chromosome pair lies
opposite of each other and crossing over happens in all 23 pairs. The chromosomes are then pulled
apart to form two haploid cells with each 23 chromosomes containing 46 chromatids/DNA strands.
Made by: Georgia Graat
