Lecture 12 - Genetic Diseases

Question 1

What are the basic units of the body?

Answer 1

Cells

Question 2

Where are chromosomes located in the cell?

Answer 2

in the nucleus

Question 3

genes reside on what?

Answer 3

chromosomes

Question 4

Genes carry the code for _____

Answer 4

proteins

Question 5

the genetic code consists of 4 letters, what are the letters and names?

Answer 5

Adenine
Cytosine
Guanine
Thymine

Question 6

the nucleus of each human cell contains strands of DNA known as __________ and they are arranged in _____

Answer 6

chromosomes and they are arranged in pairs

Question 7

There are 22 pairs of ____ chromosomes and one pair of ____ chromosomes

Answer 7

22 pairs of autosomal chromosomes and one pair of sex chromosome

Question 8

Each chromosome consists of a series of genes, and the Human Genome Project has identified about how many protein-coding genes?

Answer 8

19,000

Question 9

Each gene contains the genetic information required to produce a ____.

Answer 9

protein

Question 10

Each ____ is made specifically to perform a necessary body function

Answer 10

protein

Question 11

Mutations of a certain gene locus may affect one or both of the ______ in a pair

Answer 11

chromosomes

Question 12

What does it mean to be heterozygous for a disorder?

Answer 12

when one chromosome in the pair is affected

Question 13

what does it mean to be homozygous for a disorder?

Answer 13

if both chromosomes at a given gene locus are affected

Question 14

what is the definition of mutation>

Answer 14

permanent change in the DNA

Question 15

when a mutation affects germ cells, it can be transmitted to _____

Answer 15

progeny

Question 16

when a mutation affects a somatic cell it can result in what two things?

Answer 16

tumors or developmental malformations

Question 17

What are the names of the three types of mutations?

Answer 17

point (missence) mutation
frameshift mutation
trinucleotide repeat mutation

Question 18

what is the definitions of a point (missence) mutation and what is an example?

Answer 18

single nucleotide base substituted

Examp: sickle cell anemia

Question 19

What is the definition of a frameshift mutation?

Answer 19

insertion or deletion of one or two base pairs, altering reading frame of the DNA strand

Question 20

what is the definition and what is an example of trinucleotide repeat mutation?

Answer 20

amplification of sequence of 3 nucleotides

Examp: Fragile X syndrome

Question 21

what is a single nucleotide polymorphism?

Answer 21

variation in just one nucleotide (for example, A or T) at a single site on the DNA molecule

Question 22

over 6 million polymorphisms have been identified, but most are within which three regions?

Answer 22

exons
introns
and intergenic regions

Question 23

polymorphisms may be markers for multigenic complex diseases, such as what?

Answer 23

diabetes or hypertension

Question 24

what are different numbers of large contiguous stretches of DNA, from 1,000 to million of base pairs?

Answer 24

copy number variations

Question 25

in copy number variations how many involve gene-coding sequences, and this may account for variation in what?

Answer 25

half involve gene-coding sequences, and it may account for much PHENOTYPIC variation

Question 26

what refers to modulation of gene expression without altered DNA sequence?

Answer 26

epigenetic changes

Question 27

epigenetic changes are important in what?

Answer 27

development as well as normal homeostasis

Question 28

with epigenetic changes, methylation of promoter regions makes them inaccessible to RNA polymerase, thus reducing what?

Answer 28

protein synthesis

Question 29

what is the definition of alterations in non-coding RNAs?

Answer 29

micro-RNAs (miRNA's) inhibit translation of their target messenger RNAs into their corresponding proteins

Question 30

mendelian disorders are diseases caused by what?

Answer 30

single gene defects

Question 31

what is the definition of autosomal dominant disorders?

Answer 31

implies that the altered gene locus is on an autosome and disease will be evident clinically when only one of the chromosomes i the pair exhibit a mutation at the affected gene locus

Question 32

the majority of autosomal dominant disorders create which type of changes?

Answer 32

outward physical changes

Question 33

when is the mutant gene present in autosomal dominant disorders and what is an example?

Answer 33

it is present from birth | example: Huntington disease

Question 34

(T/F) 1. Many Autosomal dominant disorders are exhibited at birth 2. In autosomal dominant disorders the mutant gene is present from birth.

Answer 34

1. False - many autosomal dominant disorders exhibits a delayed age of onset 2. True

Question 35

With autosomal dominant disorders, how many parents are usually affected?

Answer 35

one of he parents is usually affected

Question 36

(T/F) only females can have the disorder and transmit the mutant gene

Answer 36

False - both males and females can have he disorder and transmit the mutant gene

Question 37

what percent of the offspring will have the disease if only one parent is affected with autosomal dominant diseases?

Answer 37

half or 50% of the offspring will have the disease

Question 38

what is the definition of reduced or incomplete penetrance?

Answer 38

person has a mutant gene but does not express it phenotypically

Question 39

what is the definition of variable expressivity?

Answer 39

trait is seen phenotypically in the individuals having the mutant gene but is EXPRESSED DIFFERENTLY among individuals

Question 40

what is the definition of de novo mutation?

Answer 40

affected individuals may not have affected parents because their disease arose from a new mutation

Question 41

what is the definition of autosomal recessive disorders?

Answer 41

recessive implies that the trait is expressed only if both genes at a given locus are affected (homozygous individuals)

Question 42

what is the largest group of mendelian disorder?

Answer 42

autosomal recessive disorders

Question 43

with autosomal recessive disorders do the parents of the affected individual show the disease?

Answer 43

the parents of the affected individual usually do not show the disease

Question 44

offspring of heterozygous carrier parents have what chance of getting the disease

Answer 44

offspring of heterozygous carrier parents have a one in four chance of the disease

Question 45

offspring of heterozygous carrier parent have what chance of being a carrier?

Answer 45

one and two chance of being a carried

Question 46

if the mutant gene is rare, there is a strong probability that the affected child (proband) is the product of what kind of relationship?

Answer 46

consanguineous | this means - relating to or denoting people descended from the same ancestor.

Question 47

what are the basic concepts of autosomal recessive disorders?

Answer 47

- two germline mutations (one from each parent) - equally transmitted by men and women - 25% of offspring; horizontal pattern in family

Question 48

what type of pattern is seen in families with autosomal recessive disorders?

Answer 48

horizontal pattern in family

Question 49

with autosomal recessive disorders - many of these disorders present with enzyme defects that produce what?

Answer 49

inborn error of metabolism

Question 50

in heterozygous individuals with autosomal recessive disorders, the disease is not clinically event but they may possess reduced amount of what?

Answer 50

the normal enzyme carriers are heterozygous individuals (the disease is not evident clinically)

Question 51

in autosomal recessive disorders the age of onset is more frequently when?

Answer 51

in early life

Question 52

the expression of the defect tends to be more ____ and _____ _____ is common

Answer 52

tends to be more uniform and complete penetrance is common

Question 53

although new mutations do occur, they are usually not detected for what reasons?

Answer 53

since that individual would be a carrier without clinical manifestations

Question 54

almost all X-linked disorders are recessive or dominant?

Answer 54

recessive

Question 55

are males or females carried for X linked disorders?

Answer 55

females - because they are usually heterozygous for the gene because they have 2 X chromosomes

Question 56

who is affected by x linked recessive disorders?

Answer 56

homozygous females and males (who are automatically hemizygous because they have only 1 X chromosome) are affected - mutant genes are on the X (sex) chromosome - women must inherit 2 mutated copies to be affected - all men who inherit the mutation are affected (only one X chromosome)

Question 57

although it is rare, heterozygous females may demonstrate full expression due to what?

Answer 57

unfavorable lyonization

Question 58

what is lyonization?

Answer 58

- 16 days after concpetion, all but one X chromosome is randomly inactivated in all of the cells within the zygote''- Either the maternal or paternal X may be inactivated in each cell and that X remains inactivated in the progeny of the cell

Question 59

with lyonization, the cells in normal females represent a mixture of two cell types, what are they?

Answer 59

those with active paternal X and those with active maternal X - in disorders of the X chromosome, typically females are an even mixture of normal and abnormal chromosomes

Question 60

what is unfavorable lyonization?

Answer 60

inactivation of an abnormally high percentage of normal X chromosomes, leading to clinical evidence of the disease in a heterozygote

Question 61

what is affected in x linked dominant and what is an example?

Answer 61

heterozygous homozygous hemizygous are all affected Example: Oral-Facial-Digital syndrome (OFD) type I

Question 62

What are 2 diseases that are caused by mutations in structural proteins?

Answer 62

Marfan syndrome | Ehlers-Danlos Syndrome

Question 63

what is Marfan syndrome?

Answer 63

-Autosomal dominant disorder of connective tissue due to mutation of the FBN1 gene, resulting in abnormal FIBRILLIN, a glycoprotein necessary for normal elastic fiber production

Question 64

what is the prevalence of Marfan syndrome?

Answer 64

1 in 5,000

Question 65

what are some clinical manifestations of Marfan syndrome?

Answer 65

tall, thin body habitus with abnormally long legs, arms and fingers (arachnodactyly - spider fingers) -Dislocation of lens of the eye -Aortic aneurysm and dissection leading to heart failure and aortic rupture Examples: Abraham lincoln? sudden death of basketabll players?