Principles of Human Inheritance II: Cytogenetics

duchenne muscular dystrophy, haemophilia A, haemophilia B are all caused due to ____ inheritence

sex linked

tay-sachs disease and sickle cell anemia are due to ____ inheritence

autosomal

what type of alleles produce a combination of traits when together?

co-dominant traits

ABO blood groups are an example of

co-dominance

what is the penetrance?

% of individuals in the population with a given genotype that shows signs of a specified phenotype

what is variable expressivity?

the degree to which a condition is phenotypically expressed in an individual with a given genotype

individuals who are homozygous for the recessive allele that leads to blue eye color will have blue eyes

this is an example of ___% penetrance

100%

the shade, intensity, texture of blue eyes varies widely which is an example of

variable expressivity

is the phenotype or allele dominant or recessive?

phenotype

when are sperm mitochondria shed?

before entry of sperm nucleus into egg

all mitochondria in a zygote are contributed by

the egg

each mitochondria contain several copies of

mtDNA

accumulation of _____ ______ mutations may be an important factor in the aging process

somatic mtDNA

what is heteroplasmy

presence of normal and mutated mtDNA

the nature of ____ and degree of ____ are important factors in the pathology of mitochondrial genetic disease

nature of mutations

degree of heteroplasmy

all tRNA ^ile known have a ___ and 5' proximate base to anticodon

U

the U to C mutation in mitochondrial tRNA^ile can cause

a rare form of HTN (onset 30+)

hypercholesterolimia (onset 30)

hypomagnesia (malaise+weakness)

CHECK THIS POST LEC - what is a maternally inherited pathological condition due to a single base mutation in mitochondrial tRNA gene?

the U as the 5' proximate base to anticodon is switched to U

the defect of mt tRNA U--> C is due to

the degree of destabilization of anticodon loop

and the effect on translation

(a pleiotropic effect)

some mutations in mtDNA have helped out ancestors in

adapting to cold weather

some mt DNA adaptive mutations have been correlated with

longevity

protection from neurodegenerative diseases (parkinsons and alzheimers)

marfan syndrome is a result of a mutation in fibrillin 1 which is ____ inheretence

autosomal dominant

marfan syndrome is pleiotropic in that

it is a multisystem disorder

mutant fibrillin and normal fibrillin interact to form

aberrant microfibrils

because mutatnt fibrillin interacts with normal fibrillin, the fibrillin mutation is a

dominant negative mutation

marfan syndrome clinical manifestions

skeletal, cardio, ocular, pulmonary, skin

narrow palate

long/lanky

bowed chest

scoliosis

what type of factor can affect the phenonotype without changing the genotype?

epigenetic

epigenetic inheritance occurs via

the transmission of an epigenetic factor to daughter cells

imprinting is a classic example of

epigenetic inheritance

for a paternally imprinted gene:

mother removes imprint from gene in her eggs

father puts imprint on both gene copies in hiis sperm

for maternally imprinted gene:

father removes imprint from the gene in his sperm

mother puts imprint on both gene copes in her eggs

imprinting is a ___ in the germ line

reset

imprinting is a reset in the germ line so that in the next generation,

the active copy of the gene depends on the parent of origin, not wether the copy was active in the parent

after imprinting, the active copy of the gene depends on

the parents of origin

huntingtons disease is ______ ______ inheritance

autosomal dominant

% penetration of huntingtons disease

100% pernetrant

when huntingtons disease has an earlier onset the gene is inherited by ____

perhaps a factor related to ___?

father

imprinting?!

Huntingtons Disease

clinical manifestations

neurodegenerative

hyperreflexia

chorea

dementia

psych

mutant huntintin protein (mHTT) does what

reduces acetylation of histones

interacts with transcription factors causing inactivation

Interferes with function of normal HTT protein

polygenic and multifactorial disease are caused by

complex interplay of multiple genetic and environmental factors

the inheritance of what type of disease are hard to predict?

polygenic and multifactorial disease

most congenital birth defects are

polygenic

breast cancer, colon cancer, CHD, diabetes, HTN, alzheimer, psych disorders etc are

polygenic and multifactorial

predicting the risk of genetic disease is simple for members of a family with what kind of disease?

monogenetic (having a known mendelian inheritance pattern and data related to penetrance)

assessing risks for complex genetic disease requires knowledge/estimates of what (3)

1. "heritability" of condition

2. allele frequencies in the population as a whole (pop genetics)

3. relationship of any afflicted family members to the individual being assessed

population genetics include what factors (2)

gene (allele) frequencies

genotype distribution

what is the allele/gene frequency?

the proportion of each allele in the population

what is the genotype frequency?

the proportion of each genotype in the population

how are population genetics estimated?

usually direct counting

what is the hardy-weinberg equiilibrium equation?

p^2 +2pq +q^2 =1

what is a bi-allelic locus

a specific locus in a genome that contains two observed alleles

for bi-allelic locus, what are p and q in the hardy weinberg?

the frequencies of alleles in the population

for bi-allelic locus, p + q =

1

in hardy weinberg, p^2 is the

frequency of homozygotes for allele A with a frequency of p

in hardy weinberg, q^2 is the

frequency of homozygotes for allele B with a frequency of p

in hardy weinberg, what is 2pq?

the frequency of heterozygotes

assumptions about the hardy weinberg equation (4)

- random mating

- no mutations

- no reproductive selection (against genotype)

-no large immigration from population w significantly different allele freq)

what does it mean to be polygenic

traits or diseases caused by combined effects of multiple genes

what does it mean for a disease to be multifactorial

traits or diseases that are produced by interactions between multiple genetic and environmental factors

most common adult diseases and most congenital malformations are

multifactorial

complex inheritance includes what 2 traits

polygenic

multifactorial

how many base pares in the haploid genome?

3B

what % of genes code for proteins

2%

"gene dense" centers are rich in what

G-C

what percent of the human genome is identical in all humans

99.9%

what percent of the genome is made up of repeated sequences?

50%

what percent of our genome comes from viruses that infected our evolutionary ancestors?

8%

have we precisely identified all genes?

no

how many protein coding genes do we have?

20,000-25,000

___ to ___ % percentage of protein coding genes have been identified but do not have a known function

30-50%

protein coding genes are responsible for producing more than ____ different proteins

100,000

for every protein coding gene, there is at least one ___ that codes for an important regulatory RNA

transcription unit

how are there 100k proteins but only 25k protein coding genes?

alternate splicing

alternate translational start sites

proteolytic cleavage

is there a clear correspondence between the number of protein coding genes and th elevel of complexity in an organ?

no

is there a correspondence between the amount of NON protein coding DNA and organism compexity?

yes

A son inherits mitochondria from his

A. father

B. mother

C. both parents

B. mother

Epigenetics refers to the

A. study of genetic mutations in the autosomes

B. study of sex linked genes

C. change in the phenotype without any change in the genotype

D. chromosomal translocation

C. change in the phenotype without any change in the genotype

Regulatory RNAs

A. are products of gene splicing

B. are products of specific genes

C. regulate DNA replication

D. regulate acetylation

B. are products of specific genes

___% of the human genome codes for proteins

A. 100%

B. 20%

C. 50%

D. 2%

D. 2%

how many pairs of autosomes do we have?

22

do autosomes only affect body cells?

yes

do autosomes have an influence on sex?

no

do sex chromosomes have an influence on traits outside of sex?

yes

what is responsible for two organisms having the same genes but different phenotypes?

epigenetic traits

imprinting does what to genes?

silences them

what is epistasis

When the genotype of one gene determines whether another is expressed.

what happens to mutations in mitochondrial dna?

they are sequestered

what is pleiotropy

one gene affecting multiple traits

what is heteroplasmy

presence of normal and mutated mtDNA

is huntingtons disease sex linked?

no because it is autosomal dominant

huntingtin protein (mHTT) is a ___ protein

gene regulative

huntingtons disease is a ___ function scenario

gain of function

What is cosanguinity?

being descended from the same ancestor

what is an allele

an alternative version of a gene

AA, Aa, aa are ___

genotypes

A or a are

alleles

regulatory RNA do what?

regulate expression of a gene

regulatory RNAs are products of

transcription unit