Aantekeningen Genetic and Public Health
Lecture 1: Introduction
Overall learning goals:
1. The student can explain that some disorders develop according to Mendelian principles of
inheritance but that genetics plays a different role in many disorders that are important to
public health;
2. The student can describe how and where in (public) healthcare genetics is used, and for which
target populations;
3. The student can explain that tailored prevention and care based on gene variants can be of
clinical benefit;
4. The student can demonstrate how knowledge of genetics/genomics can be translated into
healthcare and public health, and what challenges can be expected for responsible
implementation.
Lecture 2: Meet & Greet: Mendel
Learning goals:
1. You are able to explain the principles of monogenetic (Mendelian) inheritance and illustrate
them with examples
2. You are able to create a pedigree using information about a family and calculate the risks of
suffering from or passing on an inherited disorder, in the case of autosomal dominant,
autosomal recessive and X-linked recessive transmission.
A pedigree, as related to genetics, is a chart that diagrams the
inheritance of a trait or health condition through generations
of a family. The pedigree particularly shows the relationships
among family members and, when the information is
available, indicates which individuals have a trait(s) of
interest. In a pedigree the children are in order of birth. The
first-borns are always at the left. The man are shown as
squares and the females are shown as circles. When a person
is affected, the circle or square is colored black.
1
,Autosomal dominant inheritance
In a typical autosomal dominant inheritance there
are several generations affected. There is about
50% chance of passing it on when one of the
parents is heterozygous. The inheritance is from
man to woman, woman to man, woman to woman
and man to man. Examples of diseases that are
passed on in this way are huntington disease,
BRCA1&2, Lynch syndrome and Achondroplasia
Autosomal recessive inheritance
In a typical autosomal recessive inheritance both
parents have to be carriers in order to get an
affected child. When both parents are carriers, there
is a 25% chance of passing it on. If the parents don’t
have to have the disease, they can be just carriers
and thus healthy, so usually unaware of the risk
(child with a recessive disease usually comes very
unexpected). Families in which none of the children are affected, but both parents are carrier, are not
observed. Sometimes parents are consanguineous. There is usually just one generation affected.
Examples of diseases that are passed on in this way are cystic fibrosis, hemoglobinopathies and
phenylketonuria.
X-linked recessive inheritance
In a typical X-linked recessive inheritance pattern
only the sons are affected. The women are not
affected, but they are carriers and can pass on the
predisposition. There is also no inheritance from man
to man, but fathers can have daughters that are
carriers. Examples of diseases that are passed on in
this way are Duchenne Muscular Dystrophy,
Hemophilia A and B (impaired blood clotting), Color
blindness
2
, Lecture 3: Genes and diseases
Learning goals:
- The student is able to explain what is meant by genetic variation
- The student is able to explain chromosomal disorders, monogenic disorders, Mendelian
subsets of common diseases, multifactorial and complex disorders
Genes and genetic variations
Genetics can have a high impact on individuals, families and populations. A gene is a functional unit
that is regulated by transcription and encodes a product (protein or RNA). There are around 20 000 –
25 000 genes in the human genome. The genes are located on chromosomes. There are 23 pairs of
chromosomes. Only 2% of the genome codes for proteins, these are the exons. So the introns need to
be cut out. Genes are very important because they determine hereditary traits. A lot of the genes are
non-coding. They are called “junk DNA” and have a more regulatory function (switch on and switch of
the genes). The genes in the genome cause the phenotypic differences between humans and other
apes (they also have between 20 000 and 25 000 genes). So it is not the amount of genes that makes
us different from other species, but it is that one gene codes for multiple proteins or protein complexes
and that determines the complexity of the species.
Human genetic variation can be distinguished in different classes:
o Single nucleotide
variant
o Insertion-deletion
variant
o Block substitution
o Inversion variant
o Copy number
variant
Genetic variations leads to
phenotypic variations. Genetic variations in a population increases the chance that some individuals
will survive (survival of the fittest). Survival of the fittest, term made by Charles Darwin, suggested that
organisms best adjusted to their environment are the most successful in surviving and reproducing. So
the animals with the most useful genes survived and reproduced.
When you compare two individuals, each differ 1 base in 1000 basepairs. This is really handy in
forensics and paternity testing. Changes in DNA with a frequency of more than 1% are called
polymorphism. In our genome we have about 15 000 000 genetic variants (polymorphisms). Most
polymorphisms have no phenotypical consequences. Polymorphisms are normal variations compared
to pathogenic mutations which are rare and deleterious changes.
Mutations can be defined as changes in the DNA (disturbs protein function). Mutations can be caused
by DNA replication (endogenous), chemical damage (exogenous) and ionizing radiation (exogenous).
3
, The origin of the mutation can be two
folds:
• Mutations in somatic cells
▪ Somatic mutations
occur in non-germline
tissue and cannot be
inherited. These are
mutations in tumors.
• Mutations in germ/sex cells.
▪ Germline mutations
are present in egg cells
or sperm cells and can be inherited. They can cause cancer family syndrome.
There are multiple types of mutations:
• Chromosome mutations
▪ This can be either a loss (monosomy) or gain
(trisomy) of a whole chromosome, this is
called aneuploidy, or structural changes
within the chromosome, like translocations
or deletions.
• Gene mutations
▪ This is an alteration at gene level like a point mutation (singe bases), insertion,
deletion, etc.
4
Lecture 1: Introduction
Overall learning goals:
1. The student can explain that some disorders develop according to Mendelian principles of
inheritance but that genetics plays a different role in many disorders that are important to
public health;
2. The student can describe how and where in (public) healthcare genetics is used, and for which
target populations;
3. The student can explain that tailored prevention and care based on gene variants can be of
clinical benefit;
4. The student can demonstrate how knowledge of genetics/genomics can be translated into
healthcare and public health, and what challenges can be expected for responsible
implementation.
Lecture 2: Meet & Greet: Mendel
Learning goals:
1. You are able to explain the principles of monogenetic (Mendelian) inheritance and illustrate
them with examples
2. You are able to create a pedigree using information about a family and calculate the risks of
suffering from or passing on an inherited disorder, in the case of autosomal dominant,
autosomal recessive and X-linked recessive transmission.
A pedigree, as related to genetics, is a chart that diagrams the
inheritance of a trait or health condition through generations
of a family. The pedigree particularly shows the relationships
among family members and, when the information is
available, indicates which individuals have a trait(s) of
interest. In a pedigree the children are in order of birth. The
first-borns are always at the left. The man are shown as
squares and the females are shown as circles. When a person
is affected, the circle or square is colored black.
1
,Autosomal dominant inheritance
In a typical autosomal dominant inheritance there
are several generations affected. There is about
50% chance of passing it on when one of the
parents is heterozygous. The inheritance is from
man to woman, woman to man, woman to woman
and man to man. Examples of diseases that are
passed on in this way are huntington disease,
BRCA1&2, Lynch syndrome and Achondroplasia
Autosomal recessive inheritance
In a typical autosomal recessive inheritance both
parents have to be carriers in order to get an
affected child. When both parents are carriers, there
is a 25% chance of passing it on. If the parents don’t
have to have the disease, they can be just carriers
and thus healthy, so usually unaware of the risk
(child with a recessive disease usually comes very
unexpected). Families in which none of the children are affected, but both parents are carrier, are not
observed. Sometimes parents are consanguineous. There is usually just one generation affected.
Examples of diseases that are passed on in this way are cystic fibrosis, hemoglobinopathies and
phenylketonuria.
X-linked recessive inheritance
In a typical X-linked recessive inheritance pattern
only the sons are affected. The women are not
affected, but they are carriers and can pass on the
predisposition. There is also no inheritance from man
to man, but fathers can have daughters that are
carriers. Examples of diseases that are passed on in
this way are Duchenne Muscular Dystrophy,
Hemophilia A and B (impaired blood clotting), Color
blindness
2
, Lecture 3: Genes and diseases
Learning goals:
- The student is able to explain what is meant by genetic variation
- The student is able to explain chromosomal disorders, monogenic disorders, Mendelian
subsets of common diseases, multifactorial and complex disorders
Genes and genetic variations
Genetics can have a high impact on individuals, families and populations. A gene is a functional unit
that is regulated by transcription and encodes a product (protein or RNA). There are around 20 000 –
25 000 genes in the human genome. The genes are located on chromosomes. There are 23 pairs of
chromosomes. Only 2% of the genome codes for proteins, these are the exons. So the introns need to
be cut out. Genes are very important because they determine hereditary traits. A lot of the genes are
non-coding. They are called “junk DNA” and have a more regulatory function (switch on and switch of
the genes). The genes in the genome cause the phenotypic differences between humans and other
apes (they also have between 20 000 and 25 000 genes). So it is not the amount of genes that makes
us different from other species, but it is that one gene codes for multiple proteins or protein complexes
and that determines the complexity of the species.
Human genetic variation can be distinguished in different classes:
o Single nucleotide
variant
o Insertion-deletion
variant
o Block substitution
o Inversion variant
o Copy number
variant
Genetic variations leads to
phenotypic variations. Genetic variations in a population increases the chance that some individuals
will survive (survival of the fittest). Survival of the fittest, term made by Charles Darwin, suggested that
organisms best adjusted to their environment are the most successful in surviving and reproducing. So
the animals with the most useful genes survived and reproduced.
When you compare two individuals, each differ 1 base in 1000 basepairs. This is really handy in
forensics and paternity testing. Changes in DNA with a frequency of more than 1% are called
polymorphism. In our genome we have about 15 000 000 genetic variants (polymorphisms). Most
polymorphisms have no phenotypical consequences. Polymorphisms are normal variations compared
to pathogenic mutations which are rare and deleterious changes.
Mutations can be defined as changes in the DNA (disturbs protein function). Mutations can be caused
by DNA replication (endogenous), chemical damage (exogenous) and ionizing radiation (exogenous).
3
, The origin of the mutation can be two
folds:
• Mutations in somatic cells
▪ Somatic mutations
occur in non-germline
tissue and cannot be
inherited. These are
mutations in tumors.
• Mutations in germ/sex cells.
▪ Germline mutations
are present in egg cells
or sperm cells and can be inherited. They can cause cancer family syndrome.
There are multiple types of mutations:
• Chromosome mutations
▪ This can be either a loss (monosomy) or gain
(trisomy) of a whole chromosome, this is
called aneuploidy, or structural changes
within the chromosome, like translocations
or deletions.
• Gene mutations
▪ This is an alteration at gene level like a point mutation (singe bases), insertion,
deletion, etc.
4
