Hereditary

what is the leading known cause of intellectual disability and miscarriage

chromosomes abnormalities

Disjunction

normal separation of chromosomes during cell division

nondisjunction

failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis ~ usually the cause of aneuploidy

down syndrome

best known example of autosomal aneuploidy ~ 95% are caused by nondisjunction

what is the population of those diagnosed with down syndrome at risk of...

acute leukemia (10-20% greater risk) and increased risk of Alzheimers disease

what are other possible problems accompanied with down syndrome

heart problems

GI digestive issues

Increased risk of infections

what is the most common sex chromosome aneuploidy

trisomy X ~ females with three or more X chromosomes

what is XYY sex chromosome aneuploidy

male with two or more Y chromosome ~ tall and aggressive

Klinefelter Syndrome

individual with at least 2 Xs and 1 Y chromosome (XXY) ~ male appearance with female characteristics

gynecomastia

development of breast tissue in males

turners syndrome

absence of all or part of the X chromosome

what are the signs and symptoms of turners syndrome

short stature, does not ovulate, no secondary sex characteristics

what is a treatment of Turners syndrome

growth hormone therapy, estrogen therapy

chromosome breakage

break in the chromosome that the body can physiologically repair, but often heals in a way that alters the structure of the chromosome

Clastogens

harmful agents that increase the risk of chromosome breakage

cri du chat syndrome

"Cry of the cat" ~ larynx affected when developed

Deletion of short arm of chromosome 5

Low birth weight, mental retardation, and microcephaly

duplication abnormalities in chromosome structure

presence of a repeated gene/gene sequence ~ less serious (better to have more than less)

translocation abnormalities in chromosome structure

interchanging of material between non-homologous chromosomes

Robertsonian translocation

occurs when the long arms of two non-homologous chromosomes fuse at the centromere, forming a single chromosome

Fragile X Syndrome

fragile (breaks/gaps) on the long arm of the X chromosome ~ associated with intellectual disabilities ~ higher with males

autosomal dominant disorder

abnormal allele is dominant ~ results with there being no carrier ~ usually abnormalities with structural proteins

examples of autosomal dominant disorder

achondroplastic dwarfism

huntington disease

von recklinhausen's disease

what is the chance of being affected with autosomal dominant

50% chance

achondroplasia

genetic condition that results in abnormally short stature ~ disorder to bone growth ~ forming cartilage, but not converting into bone

achondroplasia is a mutation to what?

mutation in fibroblast growth factor receptor 3

what are some manifestations of achondroplasia

hypotonia

enlarged brain

running behind motor milestones ~ head to big for body

neurofibromatosis

genetic disorder with multiple benign fibrous tumors that arise from Schwann cells and other elements of the PNS ~ autosomal dominant

neurofibromatosis results in a lack of

q17 ~ gene 17 which is a tumor suppressing gene that is responsible for making neurofibromin (suppresses tumor development)

type 1 neurofibromatosis

vin Recklinghausen disease ~ benign neurofibromas that may cause damage by compression

type 2 neurofibromatosis

bilateral acoustic (mutation of chromosome 22) ~ s/s are headaches, hearing loss, and tinnitus

sign and symptoms of neurofibromatosis

multiple peripheral neural tumors, café au lait spots, increased incidence of optic gliomas and meningiomas

recurrence risk

The probability that parents of a child with a genetic disease will have yet another child with the same disease

expressivity

refers to the manner in which the gene is expressed (amount of variation) in the phenotype, which can range from mild to severe ~ cause by modifier genes

penetrance

represents the ability of a gene to express its function

incomplete penetrance

individual who has the gene for a disease but does not express the disease

epigenetics

same DNA sequence can produce different phenotypes due to chemical modifications that alter expression of genes

genomic imprinting

one parents imprints (inactivated) the gene during transmission to offspring ~ meaning only one (parent's) is active while the other is silenced

what is the recurrence risk for an autosomal recessive disorder

25% chance when BOTH parents have the autosomal recessive disease

For an autosomal recessive disorder to penetrance (represent its ability), what does the zygote need to be... heterozygote or homozygote

homozygote

what is the most common autosomal recessive occurences?

as deficiencies in enzymes (complete loss of enzyme activity) of inborn errors in metabolism

cystic fribrosis

gene encodes a chloride ion channel in some epithelial cells that alters sodium balance

phenylketonuria

elevated levels of phenylalanine that is toxic to the brain ~ if untreated leads to intellectual disability

what is absent in phenylketonuria

phenylalanine hydroxylase ~ results in lack of phenylalanine breakdown ~ need phenylalanine to breakdown and convert to tyrosine

tay-sachs disease

a variant of a class of lysosomal storage disease, known as gangliosidosis

do children with tay-sachs appear healthy at birth?

yes, but gradually conditions worsen ~ leading to blindness, deafness, and eventually death at 3-4 yrs age

what is the root problem of Tay-sachs disease

lack of hexasominidase A (enzyme) which breaksdown GM2 ganglioside (normal component of brain cells)

what accumulates in the nerve cell and gradually destroy and demyelinate them with Tay-sachs disease

sphingolipids

signs and symptoms of tay-sachs disease

exaggerated startle reflex

inability to swallow

seizure activity

paralysis

spasticity

how are those with tay-sachs diesease diagnosed

prenatal sampling to measure hexosaminidase A activity

what is defected during cystic fibrosis

defective chlorine ion transport across cell membranes

what are the s/s for cystic fibrosis

failure to thrive ~ due to malabsorption

recurrent lung/respiratory infections

viscous secretions obstructed bronchioles

disease progresses to eventual death

very salty-tasting skin

greasy, bulky stools

cystic fibrosis is a mutation of which gene

cystic fibrosis transmembrane conductance regulator (CFTR)

what is the most common life shortening, childhood-onset inherited diseases

cystic fibrosis

hemophilia A

absence of a protein necessary for blood clot ~ abnormal or missing Factor 8

a person with hemophilia A usually...

bleeds excessively, even small cuts are life threatening

duchenne's disorder is an X-linked disorder when...

DMD gene (x-linked) results in muscle cells unable to synthesize dystrophin (a structural integrity protein), which leads to skeletal cells deteriorate/death

what are the 3 epigenetic mechanisms

chemical modifications to DNA (DNA methylation)

modifications of histones

production of small RNA molecules

histone modification

modification include histone acetylation and de-acetylation to the end of a histone protein

DNA methylation

methyl group attached to cytosine ~ less likely to be transcribed into mRNA ~ renders gene silent

RNA based mechanisms

noncoding RNAs and microRNAs

What do noncoding RNA have a role in?

role in RNA splicing and DNA replication

What is a function of noncoding RNAs in relation to complementary RNAs?

Noncoding RNAs can 'sop up' complementary RNAs, thus inhibiting their function.

what do microRNA control/modulate

modulate the stability and translational efficiency of existing messengers RNA