MCB 555 ARIZONA STATE UNIVERSITY LECTURE NOTES Mendelian Genetics and Molecular Biology 2023.pdf

Mendelian Genetics and Molecular Biology

Section 4.2 -4.4: Genes and Their Action – 4.2 transcrition, 4.3 error and mutations in, 4.4 kayotrypes.

Section 29.3, Insight 5.1, Section 18.2 –Sickle Cell Disease paragraphs

Mendelian Genetics

Gregor Mendel (1822 – 1884) – father of modern genetics

He discovered the rules of ineheritance, mow called “mendel’s las of inheritance”

Independeint assortment

Became interstested in variation of pea plant anatomy

Also interested in mathematics leading to his discoveries

Examined 29000 pea plants analyzing via probability

Poblished paper in 1866 after presenting for NHSB in morvia

His importance became clear in the 30’s and 40’s

Before him, traits thought to be blended inheritance

Pea plant cross

Cross breed pure breeds tall and dwarf and got only tall plants

Phynotype – observed genetic trait

SIMPLE DOMINANT/SIMPLE RECESSIVE ( LAW OF INHERITANCE )

Genotype – genetic basis for observed phenotype

For a genetic trait, a person will have 2 chromosomes with the gene if autosomal trait

Autosome – any chromosome that isn’t a sex chromosome

Homozygouse – 2 copies of a gene are identical; Dominent – both copies having dominant allel of trait, TT;

Recessive – both copies having recessive allel of trait, tt

Heterozygous – the gene from your mother is different than the one from your father, Tt

Dominant allel mascks the recessive

Reason for this phenomena sperm/egg will be carrying one of the 2 alels for any 1 trait Horse

Example: Combined Immunodeficiency in Arabians

CC = doesn’t have CID, not a carrier of CID Cc

= Does not have CID, is a carrier of CID

cc = has disease, no immune system, dies from first infection

a human disease: David at Madison living in a sterile bubble

Human example: Cystic fibrosis

Defect in gene for Cl ion channel protein

Mutation results in preventing binding in Ca to elastic fibers

elastic fibers have lots of fibrillin protein,

each EF has 40 plus places Ca should bind to cross-link 2 adjacent fibers

Marfans results many symptoms because EF are found all over the body (flow chart)

Abe lincoln may have had this, would have shortened his lifespan

Example question:

In refrence to simple dominant/ recessive law of inheritance, If a disease is caised by a recessive gene and

two herteroozygous individuals produce offspring, what is the most likely outcome if the couple were to

rr = white

Rr = pink

RrXRr = 1:2:1 red, white, pink; RR, rr, and Rr

Human Example: Sickle cell anemia

SS = normal blood cells

ss = abnormal hemoglobin, sickle cell anemia

deadlyness due to change of RBC shape effects function of many body systems (chart) Pleiotrophy

– single mutation effecting many body systems, each mutation different phenotype

Ss = not severe symptoms, phenotype sickle cell trait

have affliction, die of heart attacks as young adults

HH = normal individuals, normal life expectancies no tendency to heart disease more than others

Alleles expressed equally, no blending, no dominance or recessive relationship Human

example: ABO blood group

Have chemicals on surface of red blood cells

In blood types AA, BB, OO, AO, and BO codominance isnlt obvious

Traits carried on the X and Y chromosones

Located on X = X-linked, located on Y = Y-linked

XX = female, XY = male

X-linked more common because they are larger chromosomes

X-linked example: Hemophilia

involving a recessive allel

lack of clotting factor

many different kinds, most common is X-linked

found in royal European family, pedigrees available with information of the affected

famous instance, only son of Czar of Russia, small part of Russian revolution 1917

long ago affliction wound not lead to ling enough life to reproduce, no females afflicted due to

treatability, female possible although most affected male choose not to reproduce

X-linked example: Duchenne’s muscular dystrophy

Inheritance incolving a recessive allele

Affects boys and not girls

Female occurance rare, males die before reproduction

Caused by defect in a cell membrane protein called dystrophin

Results in atrophy of skeletal muscle progressing to cheelchair

Eventually diaphragm is affected and respiratory problems ensue

An affected female requires an affected father and either carrier or affected mother Rarity

due to frequency of not geneALLELE,

X-linked example: involving dominant allele

No female carriers because heterozygous would express the trait since it is dominant

Females = homozygous dominant or heterozygous either way affected

Female = homozygous recessive, dominant trait not expressed

Males = XY with dominant allele on X, dominant Phenotype, affected

Male = xY withought dominant allele on X-chromosome, recessive allele, not affected

Trait encoaded on Y-chromosome, passes from male to male

Mendel’s ideas are basic to any study of genetics

laboratories where radioactive chemicals are used, can cause a number of birth defects in their offspring

besides increasing their own risk for cancer. Women that were exposed to radioactivity because they were

Begin Mutagens Section

Mutagens cause Mutations and thus can cause Birth Defects

Mutations cause 1/3 of all Birth Defects. Most Birth Defects don’t have an identifiable cause, but of those with an

Mutagens cause Mutations. Mutagens are found in the environment. Some of the Teratogens above can also be

classified as Mutagens, but not all. IF a teratogen causes a mutation, it is also a Mutagen. Environmental chemicals,

radiation, and infectious diseases can cause mutations in DNA. The mutation does not have to be inherited from the

mother’s parents or from the father’s parents. The mother or father may have had the mutation from exposure to a

mutagen AND it is also possible that neither parent had a mutation, but rather the mutation happened in the child

that has the Birth Defect. The mutation may have happened in the child before birth as a result of exposure to a

result not in “point mutations”, but rather errors in numbers of chromosomes. This is especially common for

Oogenesis in older women. The incidence begins to increase about age 30 and greatly increases year by year

after the age of 35 years. You’ve heard the saying “My biological clock is ticking”? It refers to the fact that birth

defects are less common in children of young mothers and problems for the mother with pregnancy are less

common in young mothers.

Aneuploidy = presence or absence of one entire chromosome

Sex Chromosomes and Aneuploidy

Triplo-X Syndrome – generally sterile females (Females because they have no Y chromosome

Turner’s Syndrome - sterile females of genotype XO. Almost all die before birth, but if they

Males with XYY or XYYY phenotypes – although originally discovered in prison populations

and thought to be associated with criminal behavior, we now know that there are normal males

with multiple Y chromosomes.

Detection of Point Mutations and Aneuploidy Prior to Birth

Amniocentesis – a sample of Amniotic Fluid containing fetal cells is removed from the inside of the Amniotic Sac

that surrounds the fetus. This is done at 14 – 16 Weeks post-fertilization, which is during the Second Trimester.

People usually think that this test allows abortion of the fetus if an abnormality is detected, but second trimester

abortions are not legal “on demand”. This is because the abortion procedure puts the mother more at risk than

during the first trimester (Weeks 1 – 12 post-fertilization). In practice, this test is more often done when there is a

history of genetic abnormalities in the family or a history of exposure to a teratogen. In general, this would be done

to “prepare” the parents for an affected child. One of the risks of Amniocentesis is that it can cause spontaneous

abortion. It can lead to contractions because the uterus was punctured by the needle to get the sample. A

Analyzing the mother’s cells wouldn’t necessarily tell you anything about the genes of the developing fetus. As

above, it increases the risk of spontaneous abortion. Chorionic Villus Sampling is performed later in gestation than

Ultrasonography – can be used to observe certain birth defects. For instance, the limbs can be seen if the embryo

is far enough along in development. You might also be able to detect anencephaly, spina bifida and other problems

that can be seen external to the embryo’s or fetus’ body. If the embryo is old enough, one might also be able to

determine its sex. This is the technique that would be used by people wanting to determine the sex of their child.

There is no evidence that it puts the mother or fetus at risk, so it is used “just to know” the sex of the child before it

is born AND to determine whether there are certain birth defects.

Answer: The most likely outcome would be 1 normal homozygous child, 2 normal heterozygous children that would be