Ch. 4/5: Congential/Genetic Disorders

Chromosomes

Our genetic information is stored, our chromosomes.

Humans have 23 pairs of chromosomes.

22 pairs of autosomes

And one pair of sex chromosomes: xx and xy

Karyotype

These are the visual arrangements of our chromosomes by their size, karyotypes can be used to diagnosis chromosomal disorders.

Nucleus

Our nucleus contains hereditary units of the cell, also known as our genes.

Our genes are stored along our chromosomes.

Genotypes/Phenotypes

Genotypes: these are the actual genetic information stored in an individual.

All of the cells have the same genotype except the gametes. Not all genes are expressed through cells.

Phenotype: these are the genes that are expressed.

Appearances of individuals characteristics.

Congenital Disorders and Birth Defects

These are the structural, functional, and metabolic abnormalities that are present at birth.

Birth defects: these are usually a results of structural abnormalities

Congenital disease: these usually result from functional or metabolic abnormalities

Causes for congenital disease

Genetic factors: congenital inheritance: can be classified as single gene, polygenic, multi factorial inheritance

Environmental factors: exposure during fetal development: exposure to maternal infections, disease, and drugs during pregnancy

Intrauterine (RARE): fetal crowding and abnormal positioning

Congential disorder or developmental disease: prematuries or any complications during labor and delivery.

Single gene disorder

Traits are controlled by one set of alleles, these can be classified as inheritance patterns.

-autosomal dominance

-autosomal recessive

-X-linked dominants

-X-linked recessive

Single genes control limited specific functions (chickenpox)

Single genes are systemically widespread. Ex: cystic fibrosis/ Marfan syndrome

Autosomal recessive gene

Requires both parents copy of a disorder to be affected.

If a parent has the homozygous allele that means they are carries but not affected.

If they have homozygotes, that means they are affected.

Men and women are affected equally.

If child has the heterozygote this means that they are carries but not affected.

If the child has the homozygote recessive gene this means that they affected.

Autosomal dominant gene

Only requires one parent’s copy of a gene to transmit the disorder, one allele.

No carries: does not transmit the disease to anyone.

These conditions can skip past generations.

Delayed genotypes: when the conditions skip past a generation, after presents diagnosis in parent after already imposes on the child.

Autosomal dominant disorder: Marfan’s syndrome

Marfans syndrome

Disorder of the connective tissue. This is responsible for mutating the FBN 1 gene, that is responsible for producing the protein fibrillin 1.

Systems can be mild to severe and affect multiple body systems

• this can cause heart defect

• Elongated limbs

• Arachnodactyly (elongated fingers and toes)

• Dislocation if the lens

Autosomal dominant disorder: neurofibromatosis

Tumor, neurofibromas stemmed from Schwann cells.

Neurofibromatosis 1 (NF1)

Cutaneous neurofibromatosis:common in children: benign tumor on or beneath the skin

Neurofibromatosis 2: this is asymptomatic before the age of 15

tumor of the acoustic nerve: results in the hearing loss, ringing in the ears tinnitules, and loss of balance

X-linked recessive dominant: fragile X chromosome

This is a intellectual disability that occurs and affects north America the most.

Presents in females and makes but symptoms manifest differently onto the both of them.

In males: because makes only have one x chromosome the symptoms resulted from this disorder are more expressed which means that the symptoms are more severe.

In females: because females have two x chromsomenthe normal one mitigates the affects. This is reduce penetrace: when the female has the abnormality but the symptoms that are presented are little to mild.

X linked recessive disorder

The disorder of the allele occurs on the X chromosome and not the y.

Males that have heterozygote lack the matching unaffected gene on the y chromosome

Females that are heterozygotes are unaffected carriers

While if they are recessive homozygotes they are affected.

Conditions can skip generations.

Ex: muscular dystrophy, hemophilia

Chromosomal disorders: aneuploidy

Aneuploidy: somatic cells do not have multiples of 23 chromosomes

Trisomes: cells make three copies of one chromosome

Monosome: cells make one copy of any chromosome

Monsome is lethal, while some infants can endure trisomy depending on what chromosome it is.

More chromosomes is better than less.

Autosomal aneuploidy: down syndrome

Aneuploidy: trisomy : 21 chromosomes

This causes physical or mental delay

High maternal age can increase risk

Triple or quad screening and or first trimester screening, ultra sounds and maternal blood testing

Aminocentesis and chorionic villi sampling can diagnose it before birth.

When there is a nondisjunction and translocation in meiosis.

Characteristics of down syndrome

-small head, round face, flat face profile

-slanted eyes, epicanthic fold

-short statured

-muscles are hypotonic

-delayed in development

Sex chromosomal disorder: jesters syndrome

When a female is one X chromosome instead of 2

The characteristics

-undeveloped ovaries and breast

-short statured, heart defects

-amenorrhea (no menstrual) and no infertility

Sex chromosomal disorder: klinefelter

This is a disorder when an Individual as at least 2 X chromosomes and one Y chromosome.

The karyotype: 47, xxy and 48 xxxy

The characteristic of Klinefelter syndrome

-male appearances, long limbs

-infertility due to impaired sperm production

-smaller testes

-gynecomastia (enlarged breast tissue)

The more X chromosomes the more the symptoms appear

Mitochondria dna disorder

Subject is at higher risk for mutations more than nucleus dna

There are no membrane repairs

Disorder of the mitochondrial gene may interfere with the production of cellular energy.

May produce energy reactive oxygen species, and may be detrimental to the generational signaling of apoptosis.

This is often associated with neuromuscular disorders

Multifactorial disorders

These are disorders that are associated with both genetic and environmental factors.

These are common disorders throughout the populations.

Familial inheritance is very common.

Ex: cleft palate, congenital hip dislocation, diabetes 2

Developmental disorders

These are abnormalities found after abnormalities during development in childbearing.

This can be exposure toxic chemicals, drugs, and radiation.

TORCH: this is the medical abbreviation for medical infections

Exposure to teratogen within the first two months impairs the organogenesis

Fetal alcohol syndrome

This is a group of physical, behavioral, and cognitive abnormalities that orients of secondary consumption of alcohol.

Affects of this

Prenatal and postnatal development: they are under the 10 percentile in weight or height

Central nervous system delay

-behavioral dysfunction

-intellectual disability

-developmental delays

Characteristics

-thin lip

-smooth philtrum

-eye opening

-flattened mid face

TORCH

Toxoplasmosis

Other

Rubella

Cytomegalovirus

Herpes

Diagnostic tools

Testing available

-preconception

-first trimester

-newborn

Testing recommended

-family history

-prior children have disorders

-over the age of >35

Diagnostic tools

Blood testing

-alphafetoproteing testing: high AFP levels can result in neural tool defect

-FISH testing takes the fetal cells drawn from mothers blood and cultures/analyzes it

In uterine : prenatal testing: amniocentesis p/chorionic villi

Post natal: newborn testing: metabolites or the blood of your newborn

Genetic engineering

Modifications to a gene to successfully result in desired outcome of preventing a disorder

Gene insertion: adding a gene

Gene deletion: deleting undesired gene

Gene editing: precise changes to a gene

Technically possible, but the clinical trials have not been uniformly successful

Gene therapy

solving a genetic problem by identifying the source

1. You identify the source

2. Identify it is expressed

Produce a drug that inhibits the expression of the gene

a lot of the drugs produced have been a result of cancer research