Chapter I: Single Gene Disorders

Question 1

What are homologous chromosomes?

Answer 1

when 2 chromosomes contain the same genes, but because one is paternal and one is maternal may contain different alleles

Question 2

Pseudoautosomal regions

Answer 2

The name for regions on X and Y chromosomes that are homologous

Question 3

Gene.

Answer 3

sequence of DNA that encodes a specific protein (or non translated RNA; i.e tRNA, rRNA, or snRNA)

(basic unit of inheritance)

Question 4

Locus.

Answer 4

physical location of a gene on a chromosome

Question 5

Alleles

Answer 5

variation (mutation) in the DNA sequence of a gene produces a new allele at that locus. (different forms of a gene)

Many genes have multiple alleles

Question 6

Polymorphism

Answer 6

when specific site on a chromosome has multiple alleles in the population

Question 7

Atlhough the term alleles is used most frequently with genes, can noncoding DNA also be said to have alleles of specific sequences?

Answer 7

yes

Question 8

The β-globin gene has been mapped to what location on a chromosome?

Answer 8

11p15.5 a specific location on chromosome 11

Question 9

Is the β-globin gene polymorphic? Why?

Answer 9

yes because there have many mutations of it in the population and each mutation has created a new allele in the population

Question 10

What is a genotype?

Answer 10

genetic makeup of organism

Question 11

What are the types of single-gene mutations?

Answer 11

missense
nonsense
deletion
insertion
frameshift

Question 12

Describe a missense mutation.

Answer 12

when there is a substitution of a single amino acid in the polypeptide chain

Question 13

What is the missense mutation that leads to sickle cell?

Answer 13

caused by a missense mutation that produces a substitution

Valine replaces glutamic acid in the β-globin polypeptide

Question 14

Describe nonsense mutations.

Answer 14

produce a stop codon resulting in a premature termination of translation and a truncated protein

Question 15

Frameshift mutations?

Answer 15

When the inserted or deleted number of nucleotides is not a multiple of 3

Question 16

In frame frameshift?

Answer 16

When the number of inserted or deleted bases is a multiple of 3

Question 17

Can mutations occur in promoters and transcription factors?

Answer 17

yes

Question 18

Loss of function mutations.

Answer 18

Mutations that cause a missing protein produce or cause decreased activity of the protein

Question 19

What is recurrence risk?

Answer 19

the probability that the offspring of a couple will express a genetic disease

Question 20

Label the pedigree nomenclature diagram.

Answer 20

Label the image

Question 21

Meaning of proband.

Answer 21

the first affected individual to be identified in the family

Question 22

Tricks for identifying if a pedigree is showing an AD condition.

Answer 22

• multiple generations of pedigree affected
• skipped generation not typically seen
• males and females affected equally

Question 23

An example where two unaffected AD parents transmit disease causing allele.

Answer 23

if there was reduced penetrance

Question 24

Most common type of parent genotypes that cause AD conditions?

Answer 24

Aa (heterozygous affected) individual with an aa (homozygous normal)

Question 25

Recurrence rate for AD conditions.

Answer 25

50%

Question 26

Be able to identify this pedigree.

Answer 26

Autosomal Dominant

Question 27

What are important features that would help you distinguish AR inheritance

Answer 27

* typically seen in only one generation of a pedigree * males and females affected equally

Question 28

Most common genotype of parents producing a child with an AR condition.

Answer 28

two heterozygous (carrier) parents

Question 29

Recurrence risk for offspring of the who have AR conditions?

Answer 29

25%

Question 30

List some major AD diseases.

Answer 30

* familial hypercholesterolemia (LDL receptor deficiency) * Huntington disease * neurofibromatosis type 1 * Marfann syndrome * acute intermittent porphyria

Question 31

Consanguinuity.

Answer 31

the mating of related individuals

Question 32

AR conditions.

Answer 32

* sickle cell anemia * cystic fibrosis * phenylketonuria (PKU) * Tay-Sachs disease (hexominidase A deficiency)

Question 33

What is the inheritance pattern show in this pedigree?

Answer 33

Autosomal recessive

Question 34

What are some tricks to be able to ID X-linked recessive diseases?

Answer 34

* skipped generations are commonly seen * male to male transmission not seen

Question 35

Identify the inheritance pattern shown in this pedigree

Answer 35

X linked recessive inheritance

Question 36

Name some X-linked recessive conditions.

Answer 36

* Duchenne muscular dystrophy * Lesch Nyhan Syndrome (hypoxanthine-guanine phosphoribosyltransferase [HGPRT] * Glucose - 6- phosphate dehydrogenase deficiency * Hemophilia A and B * red-green color blindness * Menkes disease * Ornithine transcarbomylase (OTC) deficiency * SCID (IL-receptor y-chain deficiency)

Question 37

Describe how offspring born to an affected male with a homozygous normal female presents if the condition is X-linked recessive?

Answer 37

all of the daughters will be heterozyogous carriers: all of the sons homozygous normal

Question 38

What is the recurrence rate for a daughter with parents who have normal male with carrier female of an X linked recessive conditon?

Answer 38

recurrence rate for daughter is 0

Question 39

What is the recurrence rate for a male born to a normal male and female who is a carrier of an X linked recessive condition?

Answer 39

The recurrence rate for a son is 50%

Question 40

If the sex of a fetus born to a normal father and carrier mother is unknown, what is the recurrence rate in a fetus born to a normal male with a carrier female of an X-linked recessive condition?

Answer 40

Recurrence rate is multiplied by 1/2, the probability the the fetus is a male versus a female. Therefore if the sex is unknown, recurrence risk would be 25% overall

Question 41

Why are women said to be mosaics with respect to the active X chromosome?

Answer 41

because they have paternal X chromosome active in 50% of cells and maternal X active in 50% of cells

Question 42

X-chromsome inactivation is thought to be mediated by 1 mechinism or more than 1 mechinism?

Answer 42

more than 1

Question 43

What are some ways the body causes X-chromosome inactivation?

Answer 43

1. A gene called XIST has been identified as the primary gene that causes X inactivation. XIST produces an RNA product tha coats the chromosome, helping produces its inactivation 2. condensation into heterochromatin 3. Methylation of gene regions on the X chromosome

Question 44

What exactly is genetic mosaiscism?

Answer 44

-the presence of 2 or more cell lines with different karyotypes in an individual. -arises from mitotic nondisjunction

Question 45

How may a female at times express an X-linked recessive mutation? What is the term for this?

Answer 45

Because of random inactivation of the X chromosomes carrying normal allele have been inactivated manifesting heterozygotes

Question 46

Why is the disease expression of a manifesting heterozygote typically milder?

Answer 46

because they have at least a small population of active X chromosomes carrying the normal allele

Question 47

Which arm of the Y chromosome contains a large block of heterochromatin?

Answer 47

the q arm

Question 48

Describe penetrance of males with Fragile X syndrome and symptoms?

Answer 48

Males: 100% penetrance * intellectual disability * large ears * prominent jaw * marcro-orchidism (usually postpubertal)

Question 49

Describe the penetrance in females with Fragile X syndrome and the symptoms.

Answer 49

Females: 60% penetrance intellectual disability

Question 50

Is male to male transmission seen in X linked dominant conditions ?

Answer 50

no

Question 51

Some tips to determine if the inheritance pattern is X-linked dominant in a pedigee?

Answer 51

examine children of an affected male none of the sons will be affected but all of his daughters will have the disease (assuming complete penetrance)

Question 52

What is the inheritance pattern shown in this pedigree?

Answer 52

X-linked dominant inheritance

Question 53

Explain how and individuals sons and daughters are affected if the male is affected and copulates with a homozygous normal female? (X linked dominant condition)

Answer 53

non of the sons affected: Recurrence rate 0% all the daughters affected recurrence rate 100%

Question 54

Recurrence rate if the sex of the fetus is unknown and there is an affected male with an X-linked dominant condition with a homozygous normal female?

Answer 54

then the recurrence rate is multiplied by 1/2 and overall recurrence rate is 50%

Question 55

Recurrence rate if a normal male mates with a heterozygous affected female with an X-linked dominant conditin?

Answer 55

50% of sons affected 50% of daughters affected