Review for path Flashcards
What is single nucleotide polymorphism
A single nucleotide polymorphism, also known as simple nucleotide polymorphism, (SNP, pronounced snip; plural snips) is a DNA sequence variation occurring commonly within a population (e.g. 1%) in which a single nucleotide — A, T, C or G — in the genome (or other shared sequence) differs between members of a biological species or paired chromosomes. For example, two sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. In this case we say that there are two alleles. Almost all common SNPs have only two alleles.
Why is SNP important
Variations in the DNA sequences of humans can affect how humans develop diseases and respond to pathogens, chemicals, drugs, vaccines, and other agents. SNP are co-herited with a disease associated gene as a result of physical proximity: SNP and the causative gene are in linkage disequilibrium. SNPs are also critical for personalized medicine.[5] However, their greatest importance in biomedical research is for comparing regions of the genome between cohorts (such as with matched cohorts with and without a disease) in genome-wide association studies
What is Copy number variation
Copy-number variations (CNVs)—a form of structural variation—are alterations of the DNA of a genome that results in the cell having an abnormal or, for certain genes, a normal variation in the number of copies of one or more sections of the DNA. CNVs correspond to relatively large regions of the genome that have been deleted (fewer than the normal number) or duplicated (more than the normal number) on certain chromosomes. For example, the chromosome that normally has sections in order as A-B-C-D might instead have sections A-B-C-C-D (a duplication of “C”) or A-B-D (a deletion of “C”).
What is CNV important
in genetic variation, CNV is associated with susceptibility or resistance to disease like cancer cells.
What is epigenetics
heritable changes in gene expression that are not caused by alterations in DNA sequence. Involved in tissue specific expression of Genes and genomic imprinting. is the study, in the field of genetics, of cellular and physiological phenotypic trait variations that are caused by external or environmental factors that switch genes on and off and affect how cells read genes instead of being caused by changes in the DNA sequence.
What is an epigenome
An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism’s offspring. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome. tumors develop due to the disruption of DNA methylation or histone modification.
What is a microRNA
is a small non-coding RNA molecule (containing about 22 nucleotides) found in plants, animals, and some viruses, which functions in RNA silencing and post-transcriptional regulation of gene expression.[1][2] don’t not encode protein and it inhibits gene expression by silencing gene expression. Encoded by eukaryotic nuclear DNA in plants and animals and by viral DNA in certain viruses whose genome is based on DNA, miRNAs function via base-pairing with complementary sequences within mRNA molecules.[3] As a result, these mRNA molecules are silenced by one or more of the following processes: 1) cleavage of the mRNA strand into two pieces, 2) destabilization of the mRNA through shortening of its poly(A) tail, and 3) less efficient translation of the mRNA into proteins by ribosomes
What processes does microRNA influence
cell proliferation, differentiation development and Apoptosis
What happens if there is problems with the microRNA
It can lead to diseases like cancer
What is mulitfactoral inheritance
it is a disease that is influenced by genetic and environmental factors. Environmental factor: may be small or large but is required. Genetic factor: involves additive results of multiple genes of small effect
What are examples of disease multifactoral inheritance
Diabetes Mellitus, Cleft lip, pyloric stenosis, congenital heart disease and Hypertension
What are the different types of chromosomal aberrations
Numerical and structural
What are the types of numerical genetic disorders
MAP - Mocsaicism, Aneuploidy and Polyploidy
What is mosaicism
denotes presence of 2 population of cells with different karyotypes in one individual . mitotic errors in early development give rise to 2 or more population of cells in the same individual.
What is aneuploidy
- is a change in the number of the chromosomes that can lead to a chromosomal disorder. chromosome complement that is not an exact multiple of 23. the mechanism is nondisjunction and anaphase lag. increase material age causes this.
What is polyploidy
chromosomes complement is a multiple of 23 - triploid - 69 tetraploid- 92
What is Turner Syndrome
45 (XO)
Complete or partial monosomy of X chromosome
2nd X is necessary for oogenesis & normal ovary development
Most common sex chromosome abnormality in females
Causes female hypogonadism
What are the clinical features of Turners syndrome
Failure to develop secondary sex characteristics, Short stature, Broad chest and widely spaced nipples, Atrophic “streak” ovaries (menopause before menarche), Cubitus Valgus (elbow angle), Primary amenorrhea, Infertility, Webbing of the neck, Hypothyroidism, Congenital heart disease
What is Klinefelter syndrome
(47,XXY or 48,XXXY)
Defined as male hypogonadism
Affected individuals have at least 2 X chromosomes and at least one Y chromosome
What are some of the clinical features of Klinefelter syndrome
Tall stature (Increase in length between the soles and the pubic bone) and abnormally long legs, Hypogonadism – present in all pt’s with Klinefelter Syndrome, small atrophic testes often associated with a small penis, lack of secondary male characteristics such as deep voice, Beard, and Male distribution of pubic hair, Gynecomastia may be present, Infertility R/T azoospermia
What is triple X syndrome? what are the clinical features
(47,XXX)Nondisjunction during meiosis.
Delayed puberty, Tall stature, Relatively small head, Epicanthal folds, GU tract malformations, Psychosocial problems, Learning disabilities, Recurrent miscarriages, Fertility problems, Premature deliveries, Autoimmune thyroid disorders
What is XYY syndrome. What are some of the clinical features
On chromsome 47. this person is identified as a boy.
Indication a baby boy has XYY
Hypotonia, delayed motor skill development, delayed speech, not easily excitable, undescended testicles at birth
Indications a young boy/teen has XYY
Autism dx, inability to grow facial/body hair, learning difficulties, attention difficulties, delayed motor skill, delayed speech, emotional issues, gynecomastia, hypotonia, hypogonadism
Indications an adult male has XYY
Decreased sex drive, decreased sperm count, infertility
What are the types of structural abnormalities
DIT
Deletion
Inversion
Translocation
What is Trisomy 21? what are the characteristics of the syndrome
Down syndrome. One of the major cause of intellectual disability. Oblique palpebral fissures, flat nasal bridge, low set ears, protruding tongue, epicanthal folds, simian crease, congenital heart disease, 1-2- fold increase risk for acute leukemia, Alzheimer disease-like lesions in all pt’s,
What are the causes of trisomy 21?
95% due to trisomy nondisjunction associated with maternal age. 4% due to Robertsonian translocation between chromosome 21 & 14 or 22
What is trisomy 18? what are the characteristics of the syndrome
Edwards syndrome. Clinical features: Clinical features
Prominent occiput, Intellectual disability, low set ears, overlapping fingers, short neck, congenital heart diseases, renal malformations, limited hip abduction, rocker feet
What is trisomy 13
patau syndrome. Clinical features
Microcephaly, intellectual disability, microphthalmia, cleft lip/palate, polydactyl, cardiac defects, renal defects, umbilical hernia, rocker feet
What is the disorder of chromosome 5? What are the characteristics of the syndrome
Cri du chat.
Clinical features
Microcephaly, round faces, characteristic cry of a kitten, mental retardation
What is the syndrome of chromosome 21?
DiGeorge syndrome. Deletion in 1 chromosome id detected by FISH Clinical features Cardiac Abnormal faces Thymic aplasia Cleft palate Hypocalcemia CATCH!!!
What are chromosomal mutations
Rearrangement of genetic material giving rise to visible structural changes
Changes are transmitted only infrequently since most are incompatible with survival
What are the types of chromosomal mutations
Missense or point mutation
frameshift
Nonsense
What is a missense or point mutation
Alters the code in a triplet of bases leading to replacement of 1 amino acid by another.
Two types: Conservative or Non- conservative
ex. Sickle cell mutation
What is a nonsense mutation
change in the DNA sequence that leas to a stop codon. Ex. beta thalassemia
What is a frameshift mutation
Small deletions or insertions involving the coding sequence leads to alteration in the reading frame of the DNA strand
NO frameshift: If the number of nucleotides involved is 3 or a multiple of 3
YES frameshift: If the number of nucleotide bases involved is OTHER THAN A MULTIPLE OF 3
Trinucleotide Repeat
Ex. Fragile X
What are enzyme defect
these are defects that reduce activity or there may b e a reduce amount of normal enzyme and causes a metabolic block.
What are the 3 consequences of enzyme defects?
Accumulation of the substrate, decreased amount of end product, failure to inactivate a tissue damaging substrate.
What are disorders that deal with alteration in structure, function or quantity of non enzyme proteins
Marfans
EDS,
Familial hypercholesterolemia
