INHERITANCE OF DISORDERS

AUTOSOMAL DOMINANT DISORDERS

Only one mutated copy of the gene will be necessary for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. The chance a child will inherit the mutated gene is 50%. Autosomal dominant conditions sometimes have reduced penetrance, which means although only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease.

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HUNTINGTON DISEASE

HUNTINGTON DISEASE-is a disorder passed down through families in which nerve cells in certain parts of the brain waste away, or degenerate. It is caused by a genetic defect on chromosome 4. The defect causes a part of DNA, called a CAG repeat, to occur many more times than it is supposed to. Normally, this section of DNA is repeated 10 to 28 times. But in persons with Huntington's disease, it is repeated 36 to 120 times.

MARFAN SYNDROME

Marfan syndrome is a disorder of connective tissue, the tissue that strengthens the body's structures. Disorders of connective tissue affect the skeletal system, cardiovascular system, eyes, and skin. CHEST HANDS

OSTEOGENESIS
Osteogenesis imperfecta is an inherited disorder of type I collagen characterized by low bone mass, bone fragility, and fractures with minimal or no trauma.

AUTOSOMAL RECESSIVE DISORDERS

Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of having a child affected by the disorder.

AUTOSOMAL RECESSIVE DISORDERS

ALBINISM
Albinism also called achromia, achromasia, or achromatosis) is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of tyrosinase, a coppercontaining enzyme involved in the production of melanin.

ADRENOGENITAL SYNDROME
Adrenogenital syndrome this condition is also more properly known as congenital adrenal hyperplasia. This is a group of conditions of similar source: a family of autosomal recessive disorders of steroid hormone production in the adrenal glands leading to a deficiency of cortisol, the stress fighting hormone. The master hormonal regulatory gland, the pituitary, sensing the deficiency, secretes massive amounts of the stimulating hormone corticotropin to bring the cortisol levels up to normal.

TAY-SACHS

Tay-Sachs disease is a deadly disease of the nervous system passed down through families. Tay-Sachs disease occurs when the body lacks hexosaminidase A, a protein that helps break down a chemical found in nerve tissue called gangliosides. Without this protein, gangliosides, particularly ganglioside GM2, build up in cells, especially nerve cells in the brain.

GALACTOSEMIA
Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Although the sugar lactose can metabolize to galactose, galactosemia is not related to and should not be confused with lactose intolerance. Galactosemia follows an autosomal recessive mode of inheritance that confers a deficiency in an enzyme responsible for adequate galactose degradation.

RH INCOMPATIBILITY
Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis,[1] is an alloimmune condition that develops in a fetus, when the IgG molecules (one of the five main types of antibodies) produced by the mother pass through the placenta. Among these antibodies are some which attack the red blood cells in the fetal circulation; the red cells are broken down and the fetus can develop reticulocytosis and anemia. This fetal disease ranges from mild to very severe, and fetal death from heart failure (hydrops fetalis) can occur. When the disease is moderate or severe, many erythroblasts are present in the fetal blood and so these forms of the disease can be called erythroblastosis fetalis

X-LINKED DOMINANT INHERITANCE

X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type. In medicine, X-linked dominant inheritance indicates that a gene responsible for a genetic disorder is located on the X chromosome, and only one copy of the allele is sufficient to cause the disorder when inherited from a parent who has the disorder. X-linked dominant traits do not necessarily affect males more than females (unlike X-linked recessive traits). The exact pattern of inheritance varies, depending on whether the father or the mother has the trait of interest. All daughters of an affected father will also be affected but none of his sons will be affected (unless the mother is also affected). In addition, the mother of an affected son is also affected (but not necessarily the other way round).

ALPORTS SYNDROME
Alport syndrome or hereditary nephritis is a genetic disorder characterized by glomerulonephritis, endstage kidney disease, and hearing loss.Alport syndrome can also affect the eyes (lenticonus). The presence of blood in the urine (hematuria) is almost always found in this condition.

X-LINKED RECESSIVE INHERETANCE

X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males (who are necessarily hemizygous for the gene mutation because they have only one X chromosome) and in females who are homozygous for the gene mutation (i.e., they have a copy of the gene mutation on each of their two X chromosomes). X-linked inheritance means that the gene causing the trait or the disorder is located on the X chromosome. Females have two X chromosomes, while males have one X and one Y chromosome. Carrier females who have only one copy of the mutation do not usually express the phenotype, although differences in X chromosome inactivation can lead to varying degrees of clinical expression in carrier females since some cells will express one X allele and some will express the other. The current estimate of sequenced Xlinked genes is 499 and the total including vaguely defined traits is 983

X L I N K E D R E C E S S I V E

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HEMOPHILLIA

Hemophilia refers to a group of bleeding disorders in which it takes a long time for the blood to clot. When you bleed, the body launches a series of reactions that help the blood clot. This is called the coagulation cascade. The process involves special proteins called coagulation factors. When one or more of these clotting factors are missing, there is usually a higher chance of bleeding.

CHRISTMAS DISEASE HEMOPHILLIA B

Haemophilia B (or hemophilia B) is a blood clotting disorder caused by a mutation of the Factor IX gene, leading to a deficiency of Factor IX. It is the second most common form of haemophilia, rarer than haemophilia A. It is sometimes called Christmas disease after Stephen Christmas, the first patient described with this disease.

DUCHENNE MUSCULAR DYSTROPHY

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy, affecting around 1 in 3,600 boys, which results in muscle degeneration and eventual death.[1] The disorder is caused by a mutation in the dystrophin gene, located on the human X chromosome, which codes for the protein dystrophin, an important structural component within muscle tissue that provides structural stability to the dystroglycan complex (DGC) of the cell membrane. While both sexes can carry the mutation, females rarely exhibit signs of the disease. Symptoms usually appear in male children before age 5 and may be visible in early infancy. Progressive proximal muscle weakness of the legs and pelvis associated with a loss of muscle mass is observed first.

D U S C H E N N E M U S C U L A R

D Y S T R O P H Y

FRAGILE X SYNDROME
Fragile X syndrome (FXS), is a genetic syndrome that is the most common known single-gene cause of autism and the most common inherited cause of mental retardation among boys. It results in a spectrum of intellectual disability ranging from mild to severe as well as physical characteristics such as an elongated face, large or protruding ears, and larger testes (macroorchidism), behavioral characteristics such as stereotypic movements (e.g. hand-flapping), and social anxiety.

MULTIFACTORIAL (POLYGENIC) INHERITANCE

Multifactorial inheritance means that "many factors" (multifactorial) are involved in causing a birth defect. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, produce the trait or condition. Often one gender (either males or females) is affected more frequently than the other in multifactorial traits. There appears to be a different "threshold of expression", which means that one gender is more likely to show the problem over the other gender. For example, hip dysplasia is nine times more common in females than males. Multifactorial traits do recur in families, because they are partly caused by genes. The chance for a multifactorial trait or condition to happen again depends upon how closely the family member with the trait is related to you. For example, the risk is higher if your brother or sister has the trait or disease, than if your first cousin has the trait or disease. Family members share a certain percentage of genes in common, depending upon their relationship.

( M U L T I F A C T O R I A L P O L Y G E N I C )

I N H E R I T A N C E

DIABETES MELLITUS
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced.This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).

CLEFT LIP AND PALATE

Cleft lip (cheiloschisis) and cleft palate (palatoschisis), which can also occur together as cleft lip and palate, are variations of a type of clefting congenital deformity caused by abnormal facial development during gestation. A cleft is a fissure or openinga gap. It is the non-fusion of the body's natural structures that form before birth. Approximately 1 in 700 children born have a cleft lip and/or a cleft palate. In decades past, the condition was sometimes referred to as harelip, based on the similarity to the cleft in the lip of a hare, but that term is now generally considered to be offensive.

NEURAL TUBE DISORDERS

Neural tube defects (NTDs) are one of the most common birth defects, occurring in approximately one in 1,000[1] live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. In the 3rd week of pregnancy called gastrulation, specialized cells on the dorsal side of the fetus begin to fuse and form the neural tube. When the neural tube does not close completely, an NTD develops.

DIABETES MELLITUS
Pyloric stenosis (or infantile hypertrophic pyloric stenosis)[1] is a condition that causes severe projectile non-bilious vomiting in the first few months of life. There is narrowing (stenosis) of the opening from the stomach to the first part of the small intestine known as the duodenum, due to enlargement (hypertrophy) of the muscle surrounding this opening (the pylorus, meaning "gate"), which spasms when the stomach empties. This hypertrophy is felt classically as an olive-shaped mass in the middle upper part or right upper quadrant of the infant's abdomen. In pyloric stenosis, it is uncertain whether there is a real congenital narrowing or whether there is a functional hypertrophy of the pyloric sphincter muscle. This condition typically develops in male babies in the first 26 weeks of life.

GENOMIC IMPRINTING

Genomic imprinting is a genetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. It is an inheritance process independent of the classical Mendelian inheritance. Imprinted alleles are silenced such that the genes are either expressed only from the non-imprinted allele inherited from the mother (e.g. H19 or CDKN1C), or in other instances from the non-imprinted allele inherited from the father. Forms of genomic imprinting have been demonstrated in insects, mammals and flowering plants.

HYDATIDIFORM MOLE
Molar pregnancy is an abnormal form of pregnancy, wherein a non-viable, fertilized egg implants in the uterus, and converts a normal pregnancy into an abnormal one, which will fail to come to term. A molar pregnancy grows into a mass in the uterus that has swollen chorionic villi. These villi grow in clusters that resemble grapes. A molar pregnancy can develop when an egg that is missing its nucleus is fertilized and that may or may not contain fetal tissue It is characterized by the presence of a hydatidiform mole (or hydatid mole, mola hydatidosa).Molar pregnancies are categorized into partial and complete moles. Mole as used here simply indicates clump of growing tissue, or a 'growth'.

CHROMOSOMAL ABNORMALITIES

A chromosome anomaly, abnormality or aberration reflects an atypical number of chromosomes or a structural abnormality in one or more chromosomes. A karyotype refers to a full set of chromosomes from an individual which can be compared to a "normal" karyotype for the species via genetic testing. A chromosome anomaly may be detected or confirmed in this manner. Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. There are many types of chromosome anomalies. They can be organized into two basic groups, numerical and structural anomalies.

KARYOTYPE
A karyotype is the number and appearance of chromosomes in the nucleus of a eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism. Karyotypes describe the number of chromosomes, and what they look like under a light microscope. Attention is paid to their length, the position of the centromeres, banding pattern, any differences between the sex chromosomes, and any other physical characteristics.[4] The preparation and study of karyotypes is part of cytogenetics. Karyogram of human male using Giemsa staining The study of whole sets of chromosomes is sometimes known as karyology. The chromosomes are depicted (by rearranging a microphotograph) in a standard format known as a karyogram or idiogram: in pairs, ordered by size and position of centromere for chromosomes of the same size.

FLOURESCENT IN SITU HYBRIDIZATION (FISH)

FISH (fluorescence in situ hybridization) is a cytogenetic technique developed by biomedical researchers in the early 1980s[1] that is used to detect and localize the presence or absence of specific DNA sequences on chromosomes. FISH uses fluorescent probes that bind to only those parts of the chromosome with which they show a high degree of sequence complementarity. Fluorescence microscopy can be used to find out where the fluorescent probe bound to the chromosomes. FISH is often used for finding specific features in DNA for use in genetic counselling, medicine, and species identification. FISH can also be used to detect and localize specific mRNAs within tissue samples. In this context, it can help define the spatial-temporal patterns of gene expression within cells and tissues.

NONDISJUNCTION ABNORMALITIES
Non-disjunction ("not coming apart") is the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2, specifically in the anaphase. This could arise from a failure of homologous chromosomes to separate in meiosis I, or the failure of sister chromatids to separate during meiosis II or mitosis. The result of this error is a cell with an imbalance of chromosomes. Such a cell is said to be aneuploid. Loss of a single chromosome (2n-1), in which the daughter cell(s) with the defect will have one chromosome missing from one of its pairs, is referred to as a monosomy. Gaining a single chromosome, in which the daughter cell(s) with the defect will have one chromosome in addition to its pairs is referred to as a trisomy.

MEIOSIS
Meiosis is a special type of cell division necessary for sexual reproduction in eukaryotes. The cells produced by meiosis are gametes or spores. In many organisms, including all animals and land plants (but not some other groups such as fungi), gametes are called sperm and egg cells.

TURNER & KLINEFELTER SYNDROME

Turner syndrome or Ullrich-Turner syndrome (also known as "Gonadal dysgenesis", 45 XO, encompasses several conditions in human females, of which monosomy X (absence of an entire sex chromosome, the Barr body) is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent (unaffected humans have 46 chromosomes, of which two are sex chromosomes). Normal females have two X chromosomes, but in Turner syndrome, one of those sex chromosomes is missing or has other abnormalities. In some cases, the chromosome is missing in some cells but not others, a condition referred to as mosaicism[2] or "Turner mosaicism". Klinefelter's syndrome, 47, XXY, or XXY syndrome is a condition in which a human has an extra X chromosome. While females have an XX chromosomal makeup, and males an XY, affected individuals have at least two X chromosomes and at least one Y chromosome.[1] Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47, XXY Males".

TURNER & KLINEFELTER SYNDROME

Klinefelter's syndrome, 47, XXY, or XXY syndrome is a condition in which a human has an extra X chromosome. While females have an XX chromosomal makeup, and males an XY, affected individuals have at least two X chromosomes and at least one Y chromosome.[1] Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47, XXY Males".

CRI-DU-CHAT SYNDROME
Cri du chat syndrome, also known as chromosome 5p deletion syndrome, 5p minus syndrome or Lejeunes syndrome, is a rare genetic disorder due to a missing part of chromosome 5. Its name is a French term (cat-cry or call of the cat) referring to the characteristic cat-like cry of affected children. It was first described by Jrme Lejeune in 1963. The condition affects an estimated 1 in 50,000 live births, strikes all ethnicities, and is more common in females by a 4:3 ratio.

TRANSLOCATION ABNORMALITIES
chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on cytogenetics or a karyotype of affected cells. There are two main types, reciprocal (also known as non-Robertsonian) and Robertsonian. Also, translocations can be balanced (in an even exchange of material with no genetic information extra or missing, and ideally full functionality) or unbalanced (where the exchange of chromosome material is unequal resulting in extra or missing genes).

DOWNS SYNDROME
Down syndrome or Down's syndrome, also known as trisomy 21, is a chromosomal condition caused by the presence of all or part of a third copy of chromosome 21.

MOSAICISM
Mosaic or mosaicism denotes the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg. Mosaicism may result from a mutation during development which is propagated to only a subset of the adult cells.

ISOCHROMOSOMES
An isochromosome is a chromosome that has lost one of its arms and replaced it with an exact copy of the other arm. This is sometimes seen in some females with Turner syndrome or in tumor cells. This may also cause an isochromosome to have two centromeres .

TRISOMY 21

TRISOMY 13

TRISOMY 18