Lecture 4 non mendelian inheritance

In mendelian inheritance, most traits are

dominant or recessive

T/F all inheritance is based on the rules of COMPLETE DOMINANCE

F/ not all inheritance is based on the rules of complete dominance

Why is all inheritance not based on the rules of complete inheritance, and give example

Because factors other than genes are involved , ex. environments (and CHANCE)

The environment can do what to genes

silence or ativate

epigenetic changes are without..

without mutations

Genes can be silenced or activated by the environments through

epigenetic changes (without mutation)

Epiegentic changes are modification to ... that affects... without doing what

Epigenetic changes are modification to DNA that affect GENE EXPRESSION, without ALTERING THE UNDERLYING DNA SEQUENCE

Epigenetic changes are modifications to DNA that affect gene expression whether a gene is...

turned off or on

Epigenetic changes include

DNA methylation and histone modifications

What are histone modifications

Chromatin remodeling

Non coding RNA like ... can trigger changes in

IncRNA, can trigger changes in the chromatin

What kind of environmental stress examples were given that can silence or activate genes

Maternal stress during pregnancy/low postpartum maternal care, childhood trauma, adulthood stressful life events

Understand this PIC?

Maternal stress could lead to altered

DNA methylation of genes

Maternal stress leading to altered DNA methylation of genes that play a role in what

obesity and metabolic health development

Altered DNA methylation of genes playing a role in obesity and metabolic health development results in

Obesity and metabolic syndome

Obesity and metabolic syndrome has what 5 dx

Obesity, HTN, Hyperlipidemia, hyperinsulinemia, diabetes

Most conditions are not

monogenic

Most condition are not monogenic and are affected by?

genes and environment

Example of polygenic traits

Height, skin, eye color, intelligence

Multifactorial conditions examples

HTN, high cholesterol, Diabetes mellitus, bipolar, autism, many forms of CA, Spina bifida

T/F in multifactorial inheritance, traits/disorder controlled by few genes

F/ controlled by multiple genes

Traits/disorder controlled by multiple genes, each with

small but additive effects, together with the envrionemental factors

(Multifactorial inheritance ) traits/disorder controlled by multiple genes, each with small but additive effects, together with env factors are also called

Polygenic inheritance

Two categories of multifactorial traits

continuous or discontinuous

continuous multifactorial traits are with

a lack of distinct phenotypes

Ex of continuous multifactorial traits

Height skin color

Discontinuous multifactorial traits are

discrete with distinct phenotypes

Ex of discontinuous multifactorial trait

Diabetes mellitus

Multifactorial traits 3 properties described

relatively common, relatively low familial recurrence risk, often have well understood env component

Multifactorial dx depends on

genes as well as the env

On a scale of being more genetics vs environmental, which dx are more environmental

Scurvy, TB

Which dx are further on the genetic scale

DMD, Down syndrome, phenylketonuria

Which dx are closer to the middle on genetic and env scale

Diabetes, spina bifida, HTN, Pyloric Stenosis(?)

What 2 things can cause diabetes

poor diet, lack of exercise

Spina bifida caused by

Folate deficiency and chemical exposure during pregnancy

HTN can be caused by

smoking, alc, stress, sleep deprivation

For multifactorial traits, the risk to relatives within and family member is ...

Raised above the general population risk

For multifactorial traits, the risk to relatives within and family member is Raised above the general population risk but is low in comparison with

mendelian traits

(risk of multifactorial dx) Risk to relative of proband are

low in comparison to mendelian inherited traits

Recurrence risk of multifactorial dx vs mendelian inheritance ( give %)

multifactorial dx recurrence risk 2-4%, mendelian disorders are higher at 25-50%

With multifactorial dx, you are at a higher risk for a trait or disorder if

your sibling has in

What does proband mean

The affected individual

(multifactorial dx) In practice, the proband is often (but not always) the only...

affected person in that family

in contrast to mendelian disorders, what can't prove multifactorial inheritance

pedigree analysis

What is used to prove multifactorial inheritance

studies of twin concordance

Continuous multifactorial traits show

normal distribution

With more genes involved, what is true of the distribution of graph provided

smoother the distribution

Understand this pic?

Combination of alleles contribute to

trait variation

From the skin pigmentation example, note that there's a lot variation in color that makes the majority of the proportion of the population, achieves a gaussian distribution. The extremes of giving The darkest (having all dominant alleles) or the lightest skin color make up a v small proportion of population. relates to th purple graph form below showing us multifactorial traits show distribution.

Twin concordance studies of multifactorial traits are performed to understand

the contribution of genes and environment to the trait

Twin concordance studies compare

disease/trait frequency or severity in monozygotic and dizygotic twins

Why are twins used for these studies

twins share a similar env, and share defined genetic material

Monozygotic (MZ) twins arise from

a single fertilized zygote which splits in two

Monozygotic twins are genetically

identical

monozygotic twins make what ratio of all twins

1/3

Dizygotic twins are from

two eggs are fertilized by different sperms

Dizygotic twins share what ratio of genetic info

1/2, genetically siblings (fraternal)

Dizygotic twins make what ratio of all twins

2/3

Twin concordance studies used to estimate how much of...

the trait is genetically controlled

Concordant trait is the trait that

is share by both members of a twin pair

Discordant trait is if

only one twin has the trait

Concordance is the

percentage of twin pairs that are concordant for a trait (that share a trait)

Twins that have been adopted and reared apart reveal

the importance of the environment

With concordant twins, how many are effected and give ex

both are affected (with bipolar disorder)

Concordant twins: if a trait occurs in monozygotic twins 70% of the times, what is the concordance

70%

In discordant twins, how many of the twins are affected and give ex

Only one of the pair is affected (with bipolar disorder)

A large difference in concordance between MZ vs DZ twins supports

a genetic component to the etiology for a dx

The more the environmental contribution to a trait the,

lesser the concordance in MZ twins

The higher the monozygotic concordance, the more important what is

the genetic contribution

In the example describe where the genetic contribution vs env is more important . Just understand how to differentiate?

Height 95% concordance= genetic contribution, IQ genetic contribution mor importance, finger ridge count genetic, Diastolic blood pressure prob env contribution

Dizygotic twin concordance is often what ratio of the monozygotic value

Half

Large difference between monozygotic and dizygotic values indicates

strong genetic component for the condition

Low twin concordance values suggest strong

env component

Twin studies are used to study

heritability of a trait

Heritability is the proportion of...

difference in a trait that is explained by genes rather than the env

Heritability is the proportion of difference in a trait that is explained by genes rather than the env i.e....

the genetic contribution of a trait

Heritability can be calculated based on

twin concordance studies

higher the heritability, stronger is the

genetic component

Understand how to do this math

For discontinuous multifactorial traits, the trait is more

discrete or clear cur

Discontinuous multifactorial traits include over how many different traits

over 20

Discontinuous multifactorial traits include

Congenital malformations and common adult dx

Ex of discontinuous multifactorial traits congenital malformations

cleft lip and palate

Ex of discontinuous multifactorial traits common adult dx

diabetes, rheumatoid arthritis, schizophrenia

Risk for discrete traits in a family could estimated using what

a liability curve

We didn't have to memorize this slide (W dr.m)

We didn't have to memorize this slide

Cleft lip and palate are both defects that occurs when

a baby lip or mouth don't form properly during pregnancy

Cleft lip and palate caused by combination of what factors

genetic and environmental factors

Combination of genetic and environmental factors causing dx with discontinuous multifactorial trait called a

liability

Within the libaility, each gene is a

liability factor

Liability factors are factors of

multifactorial trait

What environmental causes (liability factors) of cleft lip and palate

maternal smoking/drinking, maternal obesity during pregnancy, folic acid deficiency, exposure to certain meds (epilepsy)

Parents that do not express the trait in dx like cleft lip/palate (discontinuous multifactorial trait) may carry

mutations or silenced genes for lip and palate formation (genetic liability factors)

Once a certain number of genes have become underactive (mutation, epigenetic change), what happens (cleft lip related still)

a threshold level is passed and the trait, like a congenital malformation will become evident

(STILL CLEFT LIP) With increasing liability, the greater will be the

severity of trait and more likely that someone else in the family (next child) may be affected

with regards to cleft lip/palate what is unilateral incomplete

only lip

with regards to cleft lip/palate what is unilateral complete

both lip and palate