MULTIFACTORIAL COMPLEX AND POLYGENIC TRAITS Flashcards
WHAT IS POLYGENIC INHERITANCE?
certain trait is inherited through numerous genes which have a small and additive effect on the phenotype
-deviation from mendelian genetics
-additive effect -> the more genes the stronger the given trait or disorder
WHAT IS MULTIFACTORIAL / COMPLEX INHERITANCE?
when multiple genes interact with environmental factors
EXPLAIN QUALITATIVE TRAITS
-unmeasurable
-discontinuous (either present or unpresent)
-2 or more alternative manifestations
-influenced by major genes
EG: EYE COLOUR -> brown / green / blue
EXPLAIN QUANITITATIVE TRAITS
-measurable
-continuous
-influenced by minor genes + environmental factors
-important for polygenic inheritance
EG: IQ, height, blood pressure, cholesterol levels
EXPLAIN NORMAL TRAITS WITH CONTINUOUS VARIATION
-expressed via Gaussian curve
-normal distribution
-abnormalities are taken as extreme variants (extreme value, which are found on both ends of the curve)
-average in middle of curve
-quantitative traits
EG: HEIGHT, IQ, BLOOD PRESSURE, CHOLESTEROL LEVELS ETC.
WHAT ARE ISOLATED MALFORMATIONS?
Threshold theory - only a hypothetic Gaussian curve can be constructed
-continuous variation in liability
-Manifestations of a disorder appear once the total number of polygenes steps above a threshold which divides the population between healthy and sick (only on one side of the curve)
EG: cleft lip/palate, neural tube defects (spina bifida = cleft spine, anencephaly -underdeveloped skull, large missing pieces of brain), congenital heart defects
GIVE EXAMPLES OF COMMON DISORDERS OF ADULT LIFE
coronary heart disease
hypertension
obesity
cancers
parkinsons
alzeihmers
peptic ulcers
diabetes mellitus
autoimmune diseases
allergies
autism
bipolar
SCHEME OF MULTIFACTORIAL HEREDITY
HOW DO CONGENITAL MALFORMATIONS OCCUR?
prenatally in organogenesis
-teratogenic factors
HOW DO DISEASES OF ADULT LIFE OCCUR?
post natal environmental factors
CHARACTERISTICS OF MULTIFACTORIAL HEREDITY
-risk for 1st degree relatives depends on population frequency (square root of population frequency)
-risk is sharply lower or 2nd degree relatives than for 1st degree relatives and declines for more remote relatives
-recurrence risk is higher when more than 1 family member is affected (liability is high in such family - different to mendelian)
-the more severe the malformation, the greater the recurrence risk (greater liability, more genetic factors)
-if a multifactorial trait is more frequent in one sex than in the other, the risk is higher for relatives of patients of the less susceptible sex (higher liability)
-increased risk when parents are consanquineous
DISCUSS MULTIFACTORIAL INHERITANCE.
when more than 1 factor causes the trait
-people have predispositions but environmental factors also play a role
WHAT IS THE AREA OF PREVENTION?
the area between the 1st and 2nd threshold
WHAT IS THE RELATIONSHIP BETWEEN THE GENETIC ROLE AND THE ENVIRONMENTAL ROLE?
Inverse
-the stronger the genetic role of a given disorder, the less of a role environmental factors (e.g. teratogens) play in the
manifestation of a disorder
WHAT IS USED FOR THE CALCULATION OF RISK?
Edwards formula / empiric risks
r = square root of population frequency
WHAT ARE THE POSSIBILITIES OF PREVENTION?
preconception care is the only prevention of polygenic disorders
-adjustment of healthy / hormonal state / lifestyle
-protection against mutagens, teratogens
-vitamin supplementation
GIVE AN EXAMPLE OF A TERATOGEN THAT CAUSES ISOLATED DISORDERS DURING OOGENESIS
teratogen thalidomide
DESCRIBE THE DEPENDENCE ON THE GENDER FREEHOLD
DESCRIBE THE DEPENDENCE ON THE LEVEL OF SEVERITY FREEHOLD
DESCRIBE THE DEPENDENCE ON MULTIPLE FACTORS
DESCRIBE THE EXAMPLE OF CLEFT LIP
- if it is part of a syndrome it is inherited as a monogenic disorder
- if it is the only cleft palate – polygenetically inherited
-it is necessary to reach the threshold for a unilateral cleft and even higher threshold for a bilateral cleft
UNILATERAL = male - less genetic, more environmental, better prevention
LATERAL = female - more genetic, less environmental, less prevention
-child of mother with a cleft has a higher risk of a cleft than the child of a man with a cleft because women need more polygenes for the development of cleft, thus pass on more of them to their children
-if there is a boy born and a girl born with the same number of polygenes, the boy can have a cleft lip but the girl can be healthy or the boy would have a bilateral cleft, while as the girl would have a unilateral one
-prevention of preconception care
WHAT DOES PRECONCEPTION CARE PREVENT?
polygenic disorders
DEFINE HERITABILITY
the degree to which genetics causes the trait
→ we find the proportion of genetic and nongenetic factors
-determined by twin studies (concordance rates)
EG: monozygotic twins (MZ) and dizygotic twins (DZ) are observed for a trait which they have in common (concordant) and which only one has (disconcordant)
WHAT FORMULA IS USED FOR HERITABILITY?
the lower the H, the higher the effect of the environment and the higher the possibility of prevention
WHAT DOES H=1 AND H=0 MEAN?
EG: heritability 1 = cystic fibrosis, sickle cell anaemia
- heritability 0 = shot gun wound, light bulb in the buttocks
WHAT IS TERATOGENESIS?
process by which congenital malformations are produced in an embryo or fetus
HOW DOES TERATOGENESIS OCCUR?
proliferation, distribution, migration and integration of cells, reduction of excessive parts (e.g. in-between fingers – first a mass of cells, then cells die (apoptosis) forming spaces between our fingers, giving them shape
DESCRIBE THE MORPHOGENETIC SYSTEM
- embryonal – organs and organ systems
- fetal – organ components
- perinatal – integrated systems (nervous, endocrine, immune)
- postnatal - haematopoiesis, immune system
WHAT IS THE SIGNIFICANCE OF THE FIRST 2 WEEKS ON AN EMBYRO?
in the first 2 weeks a phase of “all or nothing”
→ if the embryo is damaged, development will stop
-the more developed the embryo the less severer the potential disability
WHAT HAPPENS DURING THE LATER STAGES OF EMBYRO DEVELOPMENT?
during later stages of development, mutations can leach on more easily – e.g. at the end of fetal stage mutations
-> which can cause the formation of tumors, various syndromes
WHAT IS THE EFFECT OF TERATOGENS?
embryotoxic effect – death, malformation, growth retardation, disturbance of function
WHAT IS THE SENSITIVITY OF TERATOGENS DEPENDENT ON?
- the genotype of mother and embryo,
- type and dose of teratogen
- ability of teratogens to go through placenta,
- stage of pregnancy
WHAT WAS THE FIRST DESCRIBED TERATOGEN?
THALIDOMIDE
-> drug used in the treatment of common pregnancy problems (e.g. morning sickness) women (not all but some) which were using this drug gave birth to children with severe limb reduction such as missing limbs
IS VITAMIN A - A TERATOGEN?
yes - chemical teratogen
-> excess of vitamin A and its analogues (vitamin A in the form of nutrition supplement part of a nutritional complex is not as risky as Vitamin A alone – only pure Vitamin A can be used to overdose)
-other examples of chemical teratogens include warfarin (blocks vitamin K) and cytogenetics (stop plant growth)
-other possibilities include:
1. antiepileptics
→ epileptics must change their medication ahead of time, before conceiving, as some antiepileptics are teratogenic – >treatment should not be stopped as if the mother gets an epileptic shock her baby may be at risk of hypoxia
2. psychopharmatics containing lithium
3. hormonal preparates, enzyme inhibitors,
4. Drugsdiazepam, salicylates, cocaine, LSD, cigarettes
WHAT IS THE CRITICAL PERIOD OF A TERATOGEN?
– stage of morphological system development which the teratogen can damage
WHAT IS THE SENSITIVE PERIOD OF A TERATOGEN?
post critical period, where the main dangers have been overcome and the effects of teratogen is not as severe
→ depends of the type of teratogen and its dose – for all higher doses there are longer periods of sensitivity
EXPLAIN CYTOTOXIC TERATOGENS
effects proliferation, causes organ defects which are in the midst of development
EXPLAIN SPECIFIC TERATOGENS
require the presence of specific cell receptors; have a limited effect
ARE SEVERE DEFECTS BECOMING LESS FREQUENT IN THE POPULATION?
Yes because severe teratogens are identified and eliminated, some traits disappear from the population and some are diagnosed in time, on the other side there is an increase in environmental pollution which causes different, less severe, birth defects
→ in conclusion the frequency is the same just that severe disorders are diminishing and less severe defects are increasing
GIVE EXAMPLES OF PHYSICAL TERATOGENS.
-ionization radiation
-hyperthermia (fever above 39°C lasting longer than 2 days can have teratogenic effect)
GIVE EXAMPLES OF BIOLOGICAL TERATOGENS.
viruses - rubella, small pox, influenza
bacteria - syphilis
parasites - Toxoplasma gondii -> malaria
WHAT MATERNAL FACTORS CAN LEAD TO TERATOGENS?
-nutrition - lack of 1. Ca, I, vit. D, folic acid malnutrition
-disorders - phenylketonuria, diabetes
WHAT PERCENTAGE OF NEWBORNS ARE BORN WITH BIRTH DEFECTS?
+/-2%
-> most causes are unknown but can also be due to genetics, viruses and defects of mother
WHAT PERCENTAGE OF EGGS ARE LOST DURING THE FIRST FEW WEEKS OF PREGNANCY?
27%
WHAT PERCENTAGE OF EGGS DO NOT MATURE DURING PREGNANCY?
16%
WHAT PERCENTAGE OF EGGS ARE NOT IMPLEMENTED DURING PREGNANCY?
15%
DEFINE LIABILITY
liability collectively describes all the genetic and environmental factors that contribute to the development of a multifactorial disorder.
EXPLAIN THE THRESHOLD MODEL
At the point an individual accumulates a certain liability, they will be affected by the disorder. The level of liability at which this occurs is referred to as the threshold level. The liability required to exceed the threshold level is the same in all individuals; however, individuals with affected relatives (especially first degree relatives ) will have a higher chance of exceeding the threshold level and being affected. This is due to shared genetic and environmental factors. As a general rule, the later in life a multifactorial disorder develops, the more it is dependent on environmental factors (the lower the heritability). The pattern of multifactorial inheritance allows multifactorial disorders to be differentiated from autosomal disorders which they can resemble at a quick glance.
