Genetics & Genetic diseases

Question 1

What is a karyotype?

Answer 1

the complete set of chromosomes in a species, or an individual organism. Homo sapiens are the only primates with pairs of 22 autosomes

Question 2

what is an ideogram? (remember that mutations have to be larger than 4mb to be seen on a karyotype)

Answer 2

a graphic symbol that represents an idea or concept

Question 3

What are the parts of a chromosome (long arm, short arm, etc.)?

Answer 3

p= short arm, q= long arm, centromere = links sister chormatids

Question 4

How may pairs of autosomes, and how many sex chromosomes do humans have?

Answer 4

humans have 22 pairs of autosomes (non-sex chromosomes) and 2 sex chromosomes (XX or XY)

Question 5

How does the medical and general usage of the word “gene” differ?

Answer 5

medical usage of “gene” = only those sequences that code for proteins
general usage of “gene”= any functional unit of a chromosome

Question 6

What is a locus?

Answer 6

the exact physical location of a gene on a chromosome. they are marked by “p” or “q” followed by a number

Question 7

what are alleles?

Answer 7

used when there are 2 or more variations of a gene in a population. Ex: normal vs sickle would be the two types of alleles in a population

Question 8

What is the difference between genotype and phenotype?

Answer 8

genotype refers to the particular combination of alleles that a person has for some locus. That genotype is then reflected as their phenotype. Phenotype is any observable trait

Question 9

What is a SNP?

Answer 9

single-nucleotide polymorphism (SNPs) - a DNA sequence variation occurring when a single nucleotide (A, T, C or G) differs between members of a species or paired chromosomes in an individual. The genomic distribution of SNPs is not homogenous, SNPs usually occur in non-coding regions more frequently than in coding regions.

Question 10

List the ways autosomal dominant and autosomal recessive modes of inheritance differ?

Answer 10

autosomal dominant inheritance: the locus is on autosomal chromosome (1-22) and only one mutant allele is required for expression of the phenotype. The disease is typically observed in sequential generations.
autosomal recessive inheritance: the locus is on an autosomal chromosome and both alleles must be mutant alleles to express the phenotype. In contrast to autosomal dominant disease, autosomal recessive disease are typically seen in only one generation of a pedigree (do skip generations!)

Question 11

Which parent do you inherit your mitochondrial DNA from?

Answer 11

inheritance only through maternal lines. Affected males do not pass on the genes.

Question 12

What are the genetic principles of pleiotropy?

Answer 12

Marfan syndrome is an AD disease that affects 1/10000. It is caused by a mutation in the gene that encodes fibrillin (causes CT to be stretchy). Pleiotropy= single disease causing mutation affects multiple organ systems

Question 13

What are the genetic principles of aneuploidy?

Answer 13

aneuploidy is a deviation from the euploid number (a cell that has a multiple of 23 chromosomes) by chromosome gain or loss. Monosomy- loss of a chromosome
trisomy- gain of a chromosome

Question 14

What are the genetic principles of anticipation?

Answer 14

refers to a pattern of inheritance in which individuals in the most recent generations of a pedigree develop a disease at an earlier age or with greater severity than do those in the earlier generations

Question 15

For X-linked recessive inheritance, who is affected and who is a carrier (i.e. male vs. female)?

Answer 15

X-linked recessive disease in males, because males only have one X chromosome, a male can have a recessive X-linked disease even though he only has one copy of the gene. This is because in only having one chromosome, he does not have another good copy to “hide” the effect of that mutation. Therefore men are affected and women are more likely to be carriers

Question 16

Why are females more likely to get an X-linked dominant disease than males?

Answer 16

heterzygous females are affected. Because females have two X chromosomes and thus two chances to inherit an X-linked disease causing mutation and males have only one. X-linked dominant disease are seen about twice as often in females as in males.

Question 17

What are the major features of Turner syndrome, and why is it called a mosaic disease?

Answer 17

only monosomy consistent with life (because its NOT autsomal). 45,X encompasses several conditions in human females, of which monosomy X (absence of an entire sex chromosome) is most common (50% of cases). In some cases, the chromosome is missing in some cells but not others, a condition referred to as mosaicism (46. XX and 47,XXX).
Arising from x-chromosome monosomy, Turner’s syndrome results in marked short stature (improved with growth hormone), ovarian dysgenesis, and neurocognitive problems.

Question 18

Why should we consider many sex chromosome aneuploidies as traits, and not diseases as they have been classified in the past?

Answer 18

because it is simply a deviation from standard chromosomal number and not necessarily indicative of disease processes (such as Klinefelter’s syndrome and Aliens 3 syndrome) - also it alienates individuals

Question 19

Why is fragile X syndrome called “fragile,” and what are some of its major features?

Answer 19

fragile due to unstable CGG repeat at Xq27. A portion of chromosome X is dangling by a thread. The severity of the disease correlates with # of CGG repeats. It is THE most common inherited form of mental retardation (1/1000 males). Expansion from pre- to full mutation only occurs through female meiosis

Question 20

What is the difference between imprinting of the X chromosome, and imprinting of the autosomes?

Answer 20

imprinting refers to the fact that a small number of genes are transcriptionally active only when transmitted by one of the two sexes. The homologous locus in the other parent is rendered transcriptionally inactive. For imprinted loci it is normal to have only the maternal or only the paternal active

Question 21

Prader-Wili and Angelman syndrome are examples of this epigenetic disease process ______? (the answer is in the previous question)

Answer 21

imprinting
Prader-Willi - microdeletion on paternal chromosome 15
Angelman syndrom - microdeletion on maternal chromosome 15

Question 22

There are 5 points of control for gene expression? The one most studied in terms of epigenetic influence is what stage?

Answer 22

1. Chromatin stage (most studied?)
2. Transcriptional stage
3. Translational stage
4. Post translational control into cytoplasm
5. Post translational modification

Question 23

Why does DNA naturally wrap around histones, and what epigenetic changes can occur to histone tails to encourage or discourage winding/unwinding?

Answer 23

The negative charge of DNA is attracted to the positive charge of the histones and wraps around it to become more compact. Methylation of Cytidine (CpG) down regulates transcription and stimulates transcription (CAN DO BOTH!), acetylation inhibits DNA from becoming condensed and active transcription is thus encouraged.

Question 24

What is a promoter region on a gene, and why are promoter regions generally not methylated?

Answer 24

A promoter is a region of DNA that initiates gene transcription. Promoter regions are generally not methylated because hypermethylation is one of the major epigenetic modifications that repress transcription via promotor region of tumor suppressor genes. Methylation in a CpG island can change the nucleotide from C to T and cause problems- ex: turns off tumor suppressor genes (want these to fight off tumors!) or can turn a proto-oncogene into an oncogene

Question 25

What is a non-mutagen epigenetic carcinogen?

Answer 25

a variety of compounds are considered epigenetic carcinogens (diethylstilbestrol, arsenite, hexachlorobenzene, and nickel compounds) because they result in an increased incidence of tumors, however they DO NOT show mutagen activity (they have not been shown to directly damage DNA)

Question 26

How do HAT-HDAC drugs work?

Answer 26

Acetylation, which occurs normally in a cell, neutralizes the positive charges on the histone by changing amines into amides and decreases the ability of the histones to bind to DNA. This decreased binding allows chromatin expansion, permitting genetic transcription to take place. Histone deacetylases remove those acetyl groups, increasing the positive charge of histone tails and encouraging high-affinity binding between the histones and DNA backbone. The increased DNA binding condenses DNA structure, preventing transcription. HDAC has been implicated in oral squamous cancer, and an HDAC inhibitor by the name of Vorinostat has been introduced to the market with obvious value.

Question 27

Are all genes possible proto-oncogenes?

Answer 27

A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. Not all genes have this capability, only those that are specifically designed to speed up or inhibit metabolism (synthesis of receptors, synthesis of messenger systems, involved in nuclear transcription).

Question 28

How do oncogenes and tumor suppressors differ? How many alleles in each example need to be mutated in order for cancer to form?

Answer 28

An important difference between oncogenes and tumor suppressor genes is that oncogenes result
from the activation (turning on) of proto-oncogenes, but tumor suppressor genes cause cancer
when they are inactivated (turned off).
Oncogenes only need one mutated allele to become cancerous vs tumors suppressors which need two