Human altered genes can cause diseases {genetic disease} {human inherited disease}.
tests
DNA analysis can identify more than 200 inherited diseases. Genetic-disease testing can use amniotic-fluid cells, chorionic-villi cells on placenta fetal side, umbilical-cord blood cells, or cheek cells.
chromosomal abnormalities
Chromosomal abnormalities cause inherited diseases, such as Becker muscular dystrophy, Burkitt's lymphoma, chronic granulomatous disease, DiGeorge syndrome, Duchenne muscular dystrophy, Lowe syndrome, chronic myelogenous leukemia, neurofibromatosis learning disorder, Prader-Willi, retinoblastoma, and Wilm's tumor.
Fluorescent in-situ hybridization (FISH) tests for aneuploidy, BCR/ABL translocation or Philadelphia chromosome, cryptic translocation, Down's syndrome, Klinefelter's syndrome, Miller-Dieker syndrome, PML/RARA translocation, steroid sulfatase deficiency or X-linked ichthyosis, Turner's syndrome, velocardiofacial/DiGeorge syndrome, and William's syndrome.
gene probe
PCR followed by electrophoresis can make many genes for testing and sequencing. Mutant alleles can hybridize to allele-specific oligonucleotides. Tests can use mutated-gene-region genetic probes: adenosine deaminase deficiency, alpha1-antitrypsin deficiency, cystic fibrosis, Fabry disease, familial hypercholesterolemia, Gaucher's disease, glucose-6-phosphate dehydrogenase deficiency, hemophilia A, hemophilia B, Lesch-Nyan, maple syrup urine disease, ornithine transcarbamylase deficiency, phenylketonuria, retinoblastoma, Sandhoff disease, sickle-cell anemia, Tay-Sachs disease, alpha-thalassemia, beta-thalassemia, and von Willebrand disease. Sickle-cell anemia alters restriction-enzyme sites. Alpha1-antitrypsin inhibits elastase.
gene probe: oncogenes
Cancer oncogenes include colon-cancer gene, myc gene, ras gene, neu gene, int-2 gene, BRCA-1 and BRCA-2 gene, and retinoblastoma gene. myc gene causes lung cancer and neuroblastoma. BRCA-1 and BRCA-2 genes cause breast cancer.
gene product
Tests can check gene products. Hemophilia has altered Factor VII. Lesch-Nyan syndrome has altered hypoxanthine phosphoribosyltransferase. Thalassemias have altered globin.
protein
Enzyme and protein assays can identify over 40 inherited diseases, such as Angelman syndrome, breast cancer (BRCA-1) (BRCA-2), citrullinemia, Canavan disease, Charcot-Marie-Tooth, Factor V Leiden mutation, familial polyposis coli, familial Mediterranean fever, Gaucher's disease, hemochromatosis, Hunter's syndrome, Kennedy disease or spinal and bulbar muscular dystrophy, Lesch-Nyan syndrome, Machado-Joseph disease, metachromatic leukodystrophy, multiple endocrine neoplasia type 1, phenylketonuria, Pompe's disease, Sanfilippo B, spinal muscular atrophy, spinocerebellar ataxia, Tay-Sachs disease, von Hippel-Lindau disease, Waardenburg syndrome type 1, Wilson's disease, and x-linked lymphoproliferative disease. Antibodies can detect mutant proteins, such as BRCA-1, BRCA-2, and Fragile X. Sickle-cell anemia changes protein mobility.
RFLP markers
Tests can use linked RFLP markers: alpha1-antitrypsin deficiency, Duchenne muscular dystrophy, Factor X deficiency, Friedreich's ataxia, hemophilia, Huntington's disease, myotonic dystrophy, and phenylketonuria.
Southern blotting
Southern blotting can test for sequence changes, as in sickle-cell anemia. Southern blotting can test for RFLPs, VNTRs, or triplet repeats, as in Huntington's disease and JFOM's disease. In Fragile X syndrome, FMR1-gene amplification causes Xq27 X-chromosome structural defect, which causes mental retardation.
Myotonic dystrophy and other human inherited diseases {autosomal dominant disease} can depend on one mutant allele. Familial hypercholesterolemia has few low-density lipoprotein receptors, which bind membrane cholesterol. Huntington's disease has too many Huntington-gene CAG repeats and damages neurons. Marfan's syndrome affects connective-tissue fibrillin.
Human inherited diseases {autosomal recessive disease} can have non-sex-chromosome homozygous mutant alleles. Carboxylase-enzyme deficiency requires biotin. Cystic fibrosis requires cystic-fibrosis transmembrane-conductance regulator (CFTR). Gout requires urate oxidase. Lesch-Nyhan syndrome requires hypoxanthine phosphoribosyltransferase (HPRT). Phenylketonuria requires phenylalanine hydroxylase. Neurofibromatosis requires NF1. Sickle-cell anemia requires beta-globin. Tay-Sacks disease requires hexosaminidase A. Beta-thalassemia requires beta-globin.
Skin and hair can have no pigmentation {albinism}|.
Urine can have dark color, because homogentistic oxidase is missing {alkaptonuria}.
Young children can have poor night vision and then become blind by age five to ten {Bardet-Biedl syndrome}. They can be obese and have diabetes and kidney disease. Primary cilia have damage.
Damaged kidney-cell primary cilia do not bend, blocking filtration and causing cell proliferation, so kidneys can have cysts {polycystic kidney disease}.
In inherited diseases {sprue} {celiac sprue} {celiac disease}|, gluten can inflame intestinal lining.
Sleep-disorder genes can be on chromosome 4 {essential hypersomnia syndrome} (EHS). Perhaps, EHS uses circadian locomotor output-cycle kaput gene {CLOCK gene} and gamma-aminobutyric-acid beta-1-receptor gene {gamma-aminobutyric acid beta-1 receptor} (GABRB1 receptor).
One genetic change {founder mutation} can pass to descendants. More than 1000 human diseases arose from founder mutations. Founder mutations are typically recessive but have benefits in special circumstances, so they can persist.
types
Hereditary hemochromatosis persists because HFE-gene mutation can prevent anemia.
Sickle-cell anemia persists because Hb5-gene mutation can prevent malaria. Sickle-cell anemia has five founders.
Cystic fibrosis persists because CFTR-gene mutation reduces diarrhea.
Factor V Leiden persists because FV-Leiden mutation causes thrombosis but protects against sepsis from blood bacteria.
GJB2-gene mutation causes deafness.
ABCA4-gene mutation causes blindness.
ALDH2-gene mutation causes inability to detoxify alcohol but can prevent alcoholism and possibly hepatitis B.
LCT-gene mutation allows lactose conversion. It began [-3500] in Funnel Beaker culture in north Europe.
For 75% of people, chemicals {phenylthiocarbamide} (PTC) can taste bitter. 25% of people have three changes in one gene, do not taste bitter, and can taste another toxin. Mutation arose 100,000 years ago in Africa. Because there is no variation over those years, it suggests that Homo sapiens did not interbreed with hominins in Mideast, Asia, or Europe.
Another founder mutation suggests that Basques and Celts are similar.
region
DNA regions that contain mutations can be long, for recent founding, or short, for ancient founding. Regions are originally whole chromosomes but shorten at each generation by repeated crossing over.
no founder
Hemophilia results from factor-VII-gene mutations and so has no founder.
Chromosome-4 FGFR3-gene base-pair 1138 and other DNA locations can have high mutation rate and cause achondroplasia. Such DNA diseases have no founder.
Lacking galactosidase genes, which make enzymes to metabolize galactose, causes liver damage, cataracts, and retardation {galactosemia}.
Glycogen can accumulate in muscles, heart, and lungs, because lysozymes lack enzymes {glucosidase} {acid maltase} to break down glycogen {glycogen storage disease}.
glycogen
After translation, glycogen-cleaving-enzyme precursors attach mannose at species-specific glycosylation sites. Precursors lose signal peptides after leaving endoplasmic reticulum. Mannose phosphorylation allows protein uptake into lysosomes, where enzymes split precursors into other enzymes and glycogen-cleaving enzymes.
mutation
Gene-intron mutations can cause incorrect mRNA splicing, so lysosomes have no glycogen-cleaving enzymes. Heterozygotes are only carriers, but people with two mutated genes have varying illness degrees.
types
Fabry disease, Gaucher disease, Tay-Sachs disease, and mucopolysaccharide storage diseases are glycogen storage diseases. Glycogen storage diseases {glycogen storage disease type II} include Pompe's disease and muscular dystrophy.
Males can lack blood-clotting factors and cannot stop wound bleeding {hemophilia}|.
People can be unable to metabolize histidine amino acid {histinuria}.
People can be unable to metabolize cysteine amino acid {homocystinuria}.
Gene and environment interactions can cause inherited diseases {multifactorial disease}.
Several interacting genes can cause inherited diseases {polygenic disease}.
Diseases {sex-linked recessive disorder}| can be only in males.
Deficient lysozyme proteins can lessen ganglioside production {Tay-Sachs disease}| {Niemann-Pick disease} {Hunter-Hurler syndrome}.
Chromosome 18 can have three copies {trisomy 18} {trisomy E} {Edward's syndrome} (John H. Edwards) [1960]. Fetus typically dies from heart, kidney, and other internal organs, but some live up to one year after birth and have mental retardation. Incidence is one in 3000 embryos.
People can be unable to metabolize tyrosine amino acid {tyrosinuria} {maple syrup urine disease}.
Gene {WRN gene} products, similar to DNA and RNA helicases, can cause autosomal-recessive diseases {Werner's syndrome} {Werner syndrome}, which have aging symptoms.
Color blindness, Duchenne muscular dystropy, hemophilia, and other male human-inherited diseases {X-linked disease}| can require X-chromosome mutant alleles. Duchenne muscular dystropy alters dystrophin. Hemophilia alters Factor VII.
Chromosome numbers and shapes can be abnormal {aneuploidy, chromosome}| {chromosome instability}. Almost all cancer cells have aneuploidy, perhaps from gene mutations or carcinogens that affect dividing cells. Different cancers have different chromosome-disruption patterns.
Homologous-pair chromosomes can fail to separate in second meiotic division {non-disjunction}.
Chromosomes can flip segments {chromosome inversion}.
Chromosomes can have segment deletion, duplication, or transfer {chromosome, translocation} {translocation, chromosome}.
In early cell-division stages, cells can have too few or too many chromosomes {chromosome abnormality}, such as in Down's syndrome. One birth in 250 has chromosome abnormality. New strain 0139 flourished in 1993.
Human #21 chromosome can have three copies {mongolism} {Down's syndrome} {Down syndrome}, rather than two, resulting in mental retardation. Symptoms are flattened face, thick and large tongue, extra eyelid folds, uncoordinated movements, and IQ between 20 and 60. Down's syndrome patients over 35 years have same pathological brain changes as Alzheimer's patients. Extra 21st chromosomes relate to infectious hepatitis.
Extra chromosome 13 causes mental retardation {Patau syndrome}.
Having two X-chromosomes and one Y-chromosome results in male features but with enlarged breasts and few sperm {Klinefelter's syndrome} {Klinefelter syndrome}.
Having only one X-chromosome results in immature female features {Turner's syndrome} {Turner syndrome}|.
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Date Modified: 2022.0225