1: Genetic inherited conditions
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere
within the triangle. While there are conditions that are polygenic- due to more than one genetic mutation, these are more
difficult to pinpoint.
The contributions of genetic and environmental factors to human diseases
1. Genetic/mendelian conditions- these are:
▪ Rare
▪ Genetically simple
▪ Unifactorial
▪ High recurrence rates
Cause and effect due to error in genome. The genetic diagnosis gives an additional diagnosis. e.g.
1. Phenylketonuria- due to error of metabolism that results in decreased metabolism of the amino acids phenylalanine so
causes it to build up
2. Galactosaemia- accumulation of galactose in the blood. Deficiency of galatose-1-phosphate uridyl transferase
3. Haemophilia- mutation in blood clotting factor
4. Osteogenesis imperfecta- genetic disorders affecting mainly the bones which fracture easily with either mild trauma
2. Environmental causes:
▪ Multifactorial conditions
▪ Common
▪ Genetics complex
▪ Low recurrence rate
Classification of genetic disorders
1. Multifactorial - genetic and environmental (many factors)
2. Single gene
3. Chromosomal - not just single point mutation, involves whole stretches of genome. e.g. INDELS. So large can be seen
cytogenetically- looked down a microscope
4. Mitochondrial - DNA in mitochondria
5. Somatic mutations- cancer. Can be inherited but not necessarily.
Human Diseases- BIOL2211 Page 1
,Genetic factors
• Single gene disorders- mutations in single genes often causing loss of function
• Multifactorial diseases- variants in genes causing alteration of function
• Chromosome disorders- chromosomal imbalance causes alteration in gene dosage. An additional amount of chromosome
material changing the gene dosage- how much genetic material is being made.
Types of genetic disorders
Multifactorial diseases (common)
• Only one organ system is affected
• Environmental influences- e.g. drugs, infections, genetic predispositions = susceptibility to a disease
• Variants in genes cause alteration of function
Chromosomal
• 0/6% live born but much more common in spontaneous abortions
• Thousands of genes may be involved
• Multiple organ systems affected at multiple stages in gestation
• Usually spontaneous- de novo- trisomies, deletions, duplications
• In rare cases, can be inherited- translocations
• Chromosomal imbalance causes alteration in GENE DOSAGE
Single gene- 1% of liveborn
• Dominant/recessive pedigree patterns- mendelian inheritance
• Mutations in single genes- often loss of function
• Can affect structural proteins, enzymes, receptors, transcription factors
Impact of genetic disorders
Human Diseases- BIOL2211 Page 2
,Impact of genetic disorders
Clinical genetics is rarely a genetic emergency-
Childhood
• 50% deafness/blindness/severe MR
• 25% in-patients vists
• 40-50% deaths
Adult life
• 5% disorders/diseases
• 10% common cancers
All these will have a genetic component to their conditions despite their rarity.
Chromosomes
CHARIOGRAM
The diagram shows metaphase where the sister chromatid are lined in the middle and pulled apart to produce two new daughter
cells. They have been stained to show the G BANDING. The dark regions shows a lot of DNA bunched up and paler regions are less
condensed. Each chromosome has its own specific 'barcode', its band pattern.
CHARIOTYPE
p- small arm
q- long arm
In humans we have a long and short arm except for the acrocentric chromosomes which consists almost entirely of a large q arm
including the centromere and small p arm- the centromere is located quite near one end of the chromosome. e.g. Down
syndrome is caused by an extra acrocentric chromosome.
When there is chromosomal defect, there is a phenotypic change
Human Diseases- BIOL2211 Page 3
, Down syndrome
There are a collection of features. Due to chromosome 21 defect and also known as trisomy, causes 47 chromosomes instead of
the usual 46
• Round face
• Protruding tongue
• Up slanting palpebral fissure- upward slanting of the space between the eyelids.
• Epicanthic folds- near eyes
• Developmental delay
ULTRASOUND- Some of these down syndrome symptoms can be seen and therefore diagnosed in vivo during pregnancy about
19/20 weeks screening
• Short femurs
• Nuchal translucency- back of head and nape of neck. There is increased size between the surface of the head and beginning
of the brain (meninges)
• Echogenic bowel- bowel appears brighter than usual
• Choroid plexus cyst- small, fluid filled space occurs in gland in the brain called the choroid plexus- gland makes fluid within
brain and spinal cord
• Sandal gap, single palmar crease- between 1 and 2 toe, large distance and can be seen the ultrasound due to reduced
motor activity in the head. Creases form in the palm don’t have usual 3 lines just a single line through.
Human Diseases- BIOL2211 Page 4
Etiology of diseases
For any condition the overall balance of genetic and environmental determinants can be represented by a point somewhere
within the triangle. While there are conditions that are polygenic- due to more than one genetic mutation, these are more
difficult to pinpoint.
The contributions of genetic and environmental factors to human diseases
1. Genetic/mendelian conditions- these are:
▪ Rare
▪ Genetically simple
▪ Unifactorial
▪ High recurrence rates
Cause and effect due to error in genome. The genetic diagnosis gives an additional diagnosis. e.g.
1. Phenylketonuria- due to error of metabolism that results in decreased metabolism of the amino acids phenylalanine so
causes it to build up
2. Galactosaemia- accumulation of galactose in the blood. Deficiency of galatose-1-phosphate uridyl transferase
3. Haemophilia- mutation in blood clotting factor
4. Osteogenesis imperfecta- genetic disorders affecting mainly the bones which fracture easily with either mild trauma
2. Environmental causes:
▪ Multifactorial conditions
▪ Common
▪ Genetics complex
▪ Low recurrence rate
Classification of genetic disorders
1. Multifactorial - genetic and environmental (many factors)
2. Single gene
3. Chromosomal - not just single point mutation, involves whole stretches of genome. e.g. INDELS. So large can be seen
cytogenetically- looked down a microscope
4. Mitochondrial - DNA in mitochondria
5. Somatic mutations- cancer. Can be inherited but not necessarily.
Human Diseases- BIOL2211 Page 1
,Genetic factors
• Single gene disorders- mutations in single genes often causing loss of function
• Multifactorial diseases- variants in genes causing alteration of function
• Chromosome disorders- chromosomal imbalance causes alteration in gene dosage. An additional amount of chromosome
material changing the gene dosage- how much genetic material is being made.
Types of genetic disorders
Multifactorial diseases (common)
• Only one organ system is affected
• Environmental influences- e.g. drugs, infections, genetic predispositions = susceptibility to a disease
• Variants in genes cause alteration of function
Chromosomal
• 0/6% live born but much more common in spontaneous abortions
• Thousands of genes may be involved
• Multiple organ systems affected at multiple stages in gestation
• Usually spontaneous- de novo- trisomies, deletions, duplications
• In rare cases, can be inherited- translocations
• Chromosomal imbalance causes alteration in GENE DOSAGE
Single gene- 1% of liveborn
• Dominant/recessive pedigree patterns- mendelian inheritance
• Mutations in single genes- often loss of function
• Can affect structural proteins, enzymes, receptors, transcription factors
Impact of genetic disorders
Human Diseases- BIOL2211 Page 2
,Impact of genetic disorders
Clinical genetics is rarely a genetic emergency-
Childhood
• 50% deafness/blindness/severe MR
• 25% in-patients vists
• 40-50% deaths
Adult life
• 5% disorders/diseases
• 10% common cancers
All these will have a genetic component to their conditions despite their rarity.
Chromosomes
CHARIOGRAM
The diagram shows metaphase where the sister chromatid are lined in the middle and pulled apart to produce two new daughter
cells. They have been stained to show the G BANDING. The dark regions shows a lot of DNA bunched up and paler regions are less
condensed. Each chromosome has its own specific 'barcode', its band pattern.
CHARIOTYPE
p- small arm
q- long arm
In humans we have a long and short arm except for the acrocentric chromosomes which consists almost entirely of a large q arm
including the centromere and small p arm- the centromere is located quite near one end of the chromosome. e.g. Down
syndrome is caused by an extra acrocentric chromosome.
When there is chromosomal defect, there is a phenotypic change
Human Diseases- BIOL2211 Page 3
, Down syndrome
There are a collection of features. Due to chromosome 21 defect and also known as trisomy, causes 47 chromosomes instead of
the usual 46
• Round face
• Protruding tongue
• Up slanting palpebral fissure- upward slanting of the space between the eyelids.
• Epicanthic folds- near eyes
• Developmental delay
ULTRASOUND- Some of these down syndrome symptoms can be seen and therefore diagnosed in vivo during pregnancy about
19/20 weeks screening
• Short femurs
• Nuchal translucency- back of head and nape of neck. There is increased size between the surface of the head and beginning
of the brain (meninges)
• Echogenic bowel- bowel appears brighter than usual
• Choroid plexus cyst- small, fluid filled space occurs in gland in the brain called the choroid plexus- gland makes fluid within
brain and spinal cord
• Sandal gap, single palmar crease- between 1 and 2 toe, large distance and can be seen the ultrasound due to reduced
motor activity in the head. Creases form in the palm don’t have usual 3 lines just a single line through.
Human Diseases- BIOL2211 Page 4
